Neophyte Agent Intelligence
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10.1016/j.mtbio.2023.100582:::title::::::0:::0
| 8,650,399,219,291,345,000
|
Recent progress of antibacterial hydrogels in wound dressings — TITLE
Recent progress of antibacterial hydrogels in wound dressings
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
title
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::abstract::::::0:::0
| 5,342,171,232,047,600,000
|
Recent progress of antibacterial hydrogels in wound dressings — ABSTRACT
Hydrogels are hydrophilic three-dimensional polymer networks that combine favorable biocompatibility, mechanical properties resembling soft tissue extracellular matrix, and intrinsic tissue repair advantages. In skin wound management, hydrogels endowed with antibacterial functions are particularly attractive as wound dressings because they can provide a moist healing environment, absorb exudate, promote hemostasis and re-epithelialization, and reduce infection risk. This review summarizes recent progress in the design and fabrication of antibacterial hydrogel wound dressings, emphasizing (i) crosslinking strategies and how they determine mechanical/stability properties and functionality (permanent covalent, dynamic covalent, physical, and hybrid crosslinking); (ii) antibacterial components and mechanisms, including inherent antibacterial polymers (chitosan, antimicrobial peptides, essential oils), synthetic antibacterial groups (quaternary ammonium compounds, ionic liquids, N-halamines), and antibacterial agents released from hydrogels (metal ions, antibiotics, peptides); and (iii) stimulus-responsive antibacterial approaches (photothermal/photodynamic, sonodynamic, electrical, pH/thermal/salt-responsive) used to improve antibacterial efficacy and reduce resistance.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
abstract
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::abstract::::::0:::1
| 8,585,301,118,761,914,000
|
Recent progress of antibacterial hydrogels in wound dressings — ABSTRACT
In skin wound management, hydrogels endowed with antibacterial functions are particularly attractive as wound dressings because they can provide a moist healing environment, absorb exudate, promote hemostasis and re-epithelialization, and reduce infection risk. This review summarizes recent progress in the design and fabrication of antibacterial hydrogel wound dressings, emphasizing (i) crosslinking strategies and how they determine mechanical/stability properties and functionality (permanent covalent, dynamic covalent, physical, and hybrid crosslinking); (ii) antibacterial components and mechanisms, including inherent antibacterial polymers (chitosan, antimicrobial peptides, essential oils), synthetic antibacterial groups (quaternary ammonium compounds, ionic liquids, N-halamines), and antibacterial agents released from hydrogels (metal ions, antibiotics, peptides); and (iii) stimulus-responsive antibacterial approaches (photothermal/photodynamic, sonodynamic, electrical, pH/thermal/salt-responsive) used to improve antibacterial efficacy and reduce resistance. Representative hydrogel forms (microneedles, Janus patches, nanofiber-reinforced hydrogels, injectable matrices, sponge and film dressings) and typical mechanical properties of single-, double-, and multi-network hydrogels are summarized.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
abstract
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::abstract::::::0:::2
| -2,542,734,020,010,896,000
|
Recent progress of antibacterial hydrogels in wound dressings — ABSTRACT
This review summarizes recent progress in the design and fabrication of antibacterial hydrogel wound dressings, emphasizing (i) crosslinking strategies and how they determine mechanical/stability properties and functionality (permanent covalent, dynamic covalent, physical, and hybrid crosslinking); (ii) antibacterial components and mechanisms, including inherent antibacterial polymers (chitosan, antimicrobial peptides, essential oils), synthetic antibacterial groups (quaternary ammonium compounds, ionic liquids, N-halamines), and antibacterial agents released from hydrogels (metal ions, antibiotics, peptides); and (iii) stimulus-responsive antibacterial approaches (photothermal/photodynamic, sonodynamic, electrical, pH/thermal/salt-responsive) used to improve antibacterial efficacy and reduce resistance. Representative hydrogel forms (microneedles, Janus patches, nanofiber-reinforced hydrogels, injectable matrices, sponge and film dressings) and typical mechanical properties of single-, double-, and multi-network hydrogels are summarized.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
abstract
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::abstract::::::0:::3
| -1,576,778,824,061,910,000
|
Recent progress of antibacterial hydrogels in wound dressings — ABSTRACT
Representative hydrogel forms (microneedles, Janus patches, nanofiber-reinforced hydrogels, injectable matrices, sponge and film dressings) and typical mechanical properties of single-, double-, and multi-network hydrogels are summarized. We discuss advantages, limitations, and safety concerns (e.g., cytotoxicity and long-term metal retention), and provide an outlook on future directions: broader antibacterial spectra in testing, long-lasting and on-demand antibacterial effects, multifunctional hydrogels tailored to sequential wound-healing stages, improved biodegradation matching, scalable manufacturing and sterilization, and integration with smart electronics and data-driven design methods. The review aims to guide rational selection of materials and crosslinking chemistries for next-generation antibacterial hydrogel wound dressings.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
abstract
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::introduction::::::0:::0
| -5,288,796,335,111,715,000
|
Recent progress of antibacterial hydrogels in wound dressings — INTRODUCTION
Hydrogels are highly hydrophilic, three-dimensional network polymers that possess good biocompatibility, high water uptake (swelling), and mechanical behavior similar to the extracellular matrix of soft tissues [1-9]. As wound dressings, hydrogels can provide a moist and protective environment, absorb wound exudate, permit oxygen diffusion, promote hemostasis, reduce pain by dampening nerve-end stimulation, and accelerate granulation tissue formation and re-epithelialization [10-23]. Hydrogels can adhere physically to tissue interfaces and, by appropriate chemical functionalization, form covalent or noncovalent bonds with tissue proteins to improve sealing and hemostasis [17]. They can also be tailored to modulate local inflammation (for example, via pH control or inclusion of anti-inflammatory agents) and to control local temperature and vascular responses that influence patient comfort and healing progress [18-20].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
introduction
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::introduction::::::1:::0
| 8,217,809,097,628,531,000
|
Recent progress of antibacterial hydrogels in wound dressings — INTRODUCTION
Skin barrier disruption makes wounds susceptible to colonization and infection by a variety of microorganisms (bacteria, fungi, viruses) from the external environment [24-26]. Common wound pathogens include Staphylococcus aureus, streptococci, coagulase-negative staphylococci, and Pseudomonas aeruginosa. Since the discovery of penicillin in 1928, antibiotics have become primary tools in infection control, but systemic administration can lead to bacterial resistance and systemic toxicity [27]. Localized antibacterial delivery at the wound site—using materials that either are themselves antibacterial or that release antibacterial agents—can reduce systemic exposure and support efficient bacterial control. Antibacterial hydrogel dressings are commonly classified by (i) source of antibacterial action: inherent antibacterial hydrogels (the matrix itself has antibacterial activity), agent-release hydrogels (antibacterial drugs, metal ions, nanoparticles are loaded and released), and stimulus-responsive hydrogels (external stimuli trigger antibacterial action or agent release); and (ii) crosslinking/network type: physically crosslinked (electrostatic interactions, hydrogen bonding, crystallization, host–guest interactions), chemically crosslinked (permanent covalent bonds), and hybrid networks combining physical and covalent interactions.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
introduction
| null | 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::introduction::::::1:::1
| 738,873,492,903,187,600
|
Recent progress of antibacterial hydrogels in wound dressings — INTRODUCTION
Localized antibacterial delivery at the wound site—using materials that either are themselves antibacterial or that release antibacterial agents—can reduce systemic exposure and support efficient bacterial control. Antibacterial hydrogel dressings are commonly classified by (i) source of antibacterial action: inherent antibacterial hydrogels (the matrix itself has antibacterial activity), agent-release hydrogels (antibacterial drugs, metal ions, nanoparticles are loaded and released), and stimulus-responsive hydrogels (external stimuli trigger antibacterial action or agent release); and (ii) crosslinking/network type: physically crosslinked (electrostatic interactions, hydrogen bonding, crystallization, host–guest interactions), chemically crosslinked (permanent covalent bonds), and hybrid networks combining physical and covalent interactions. Choice of raw materials (natural, synthetic, or semi-synthetic polymers) and crosslinking chemistry directly affects adhesion, mechanical robustness, swelling, hemostatic behavior, biodegradation, and antibacterial performance.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
introduction
| null | 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::introduction::::::1:::2
| 860,791,712,652,414,300
|
Recent progress of antibacterial hydrogels in wound dressings — INTRODUCTION
Antibacterial hydrogel dressings are commonly classified by (i) source of antibacterial action: inherent antibacterial hydrogels (the matrix itself has antibacterial activity), agent-release hydrogels (antibacterial drugs, metal ions, nanoparticles are loaded and released), and stimulus-responsive hydrogels (external stimuli trigger antibacterial action or agent release); and (ii) crosslinking/network type: physically crosslinked (electrostatic interactions, hydrogen bonding, crystallization, host–guest interactions), chemically crosslinked (permanent covalent bonds), and hybrid networks combining physical and covalent interactions. Choice of raw materials (natural, synthetic, or semi-synthetic polymers) and crosslinking chemistry directly affects adhesion, mechanical robustness, swelling, hemostatic behavior, biodegradation, and antibacterial performance. Recent literature has emphasized strategies to (a) create inherently antibacterial matrices with cationic or membrane-active moieties, (b) load or immobilize antibacterial agents (metals, antibiotics, peptides), and (c) integrate stimulus-responsive elements (photothermal agents, photosensitizers, sonosensitizers, electroactive components) to achieve on-demand antibacterial activity and reduce the selective pressure for resistance [28-43].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
introduction
| null | 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::introduction::::::2:::0
| -1,628,761,503,661,308,400
|
Recent progress of antibacterial hydrogels in wound dressings — INTRODUCTION
This review synthesizes recent advances in crosslinking strategies and material choices for antibacterial hydrogel wound dressings, summarizes the principal antibacterial components and mechanisms used in hydrogels, reviews stimulus-responsive antibacterial modalities, and highlights representative hydrogel formats and their mechanical/functional properties. We conclude with a discussion of current limitations and an outlook for future development toward clinically translatable antibacterial hydrogel dressings.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
introduction
| null | 2
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::results::::::0:::0
| -3,428,623,637,175,457,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Overview: antibacterial hydrogel wound dressings obtain antibacterial activity either from intrinsic antibacterial matrix components, from loaded/released antimicrobial agents, or from stimulus-triggered antibacterial modalities. Below we summarize representative recent advances and typical performance metrics. 1) Inherent antibacterial hydrogels
Natural polymer–based inherent antibacterial hydrogels: Natural polymers such as chitosan, antimicrobial peptides, tannic acid, lysozyme and some plant-derived essential oils provide inherent antibacterial mechanisms (membrane disruption, peptidoglycan hydrolysis, protein denaturation). Chitosan—a cationic polysaccharide obtained by deacetylation of chitin—exerts antibacterial activity via protonated amino groups that interact electrostatically with negatively charged bacterial membranes and can disrupt membrane integrity. For example, chitosan crosslinked with four-armed polyethylene glycol aldehyde (4r-PEG-CHO) via Schiff-base chemistry formed adhesive antibacterial dressings with near-complete inhibition of E. coli and S. aureus at sufficient chitosan content [131].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::0:::1
| -9,003,373,857,181,364,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Chitosan—a cationic polysaccharide obtained by deacetylation of chitin—exerts antibacterial activity via protonated amino groups that interact electrostatically with negatively charged bacterial membranes and can disrupt membrane integrity. For example, chitosan crosslinked with four-armed polyethylene glycol aldehyde (4r-PEG-CHO) via Schiff-base chemistry formed adhesive antibacterial dressings with near-complete inhibition of E. coli and S. aureus at sufficient chitosan content [131]. Carboxymethyl cellulose hydrogels covalently bound to ε-poly-L-lysine exhibited 99.5% inactivation of P. aeruginosa and 98.5% of S. aureus after 3 h exposure in one reported study [126,130]. Tannic acid, a polyphenol, contributes via hydrogen bonding within hydrogels (imparting adhesion and cohesion) and via direct antibacterial and antioxidant action on bacterial cell envelopes; composite hydrogels containing tannic acid have shown strong adhesion (examples reporting >160 kPa adhesive strength) and membrane-disrupting antibacterial activity [132]. Lysozyme-containing bilayer hydrogels reduced E. coli survival in proportion to lysozyme concentration, illustrating enzymatic antibacterial strategies [133].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::0:::2
| -6,152,415,992,665,940,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Tannic acid, a polyphenol, contributes via hydrogen bonding within hydrogels (imparting adhesion and cohesion) and via direct antibacterial and antioxidant action on bacterial cell envelopes; composite hydrogels containing tannic acid have shown strong adhesion (examples reporting >160 kPa adhesive strength) and membrane-disrupting antibacterial activity [132]. Lysozyme-containing bilayer hydrogels reduced E. coli survival in proportion to lysozyme concentration, illustrating enzymatic antibacterial strategies [133]. Natural antibacterial ingredients are generally biocompatible and biodegradable but often require extraction/purification and may have limited potency compared with some synthetic agents.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::1:::0
| 5,919,064,886,345,679,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Synthetic polymer–based inherent antibacterial hydrogels: Synthetic antibacterial motifs (ionic liquids, quaternary ammonium salts, N-halamines, imidazolium derivatives, biguanides, phenolic and nitrile chemistries) have been incorporated into hydrogel matrices to achieve stronger and more tunable antibacterial activity. Ionic liquids (ILs), composed of organic cations/anions, disrupt membranes through electrostatic and amphiphilic interactions. A hyaluronic acid/PEG/poly(ionic liquid) semi-interpenetrating network killed >95% of E. coli and S. aureus in vitro within 2 h and showed >97% eradication of S. aureus in an in vivo wound model [136]. N-halamine chemistries (which transfer halide ions or form covalent N–X bonds) and quaternary ammonium functionalities have been used to impart long-lived contact antibacterial activity when immobilized on hydrogel backbones [137-149]. Synthetic antibacterial motifs can be covalently bound to hydrogels to extend lifetime and reduce leaching, but potential cytotoxicity and hemocompatibility must be evaluated for each chemistry.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::2:::0
| 7,661,942,086,519,383,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Hydrogels modified with antibacterial groups: When base matrices lack antibacterial activity (e.g., polyvinyl alcohol), covalent grafting of antibacterial monomers (quaternary ammonium monomers, guanidine-based monomers, imidazolium monomers) has been used to create durable contact-active hydrogels with broad-spectrum bactericidal activity (>99% in several reports) [146-149]. Immobilization reduces release-related systemic exposure and can extend the working life of dressings. 2) Antibacterial hydrogels based on antibacterial agent release
Metal ion–based composite hydrogels: Metal ions and metal/metal-oxide nanoparticles (Ag, Cu, Zn, Mg, Au, ZnO, CuS, etc.) remain widely used because of broad-spectrum activity mediated by protein/DNA binding and ROS generation. Silver nanoparticles incorporated in PVA/starch matrices or immobilized via polydopamine coatings provide sustained release and strong bactericidal effects at relatively low concentrations; careful tuning is required to avoid fibroblast cytotoxicity [194-195].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 2
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::2:::1
| -8,116,566,410,493,819,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
remain widely used because of broad-spectrum activity mediated by protein/DNA binding and ROS generation. Silver nanoparticles incorporated in PVA/starch matrices or immobilized via polydopamine coatings provide sustained release and strong bactericidal effects at relatively low concentrations; careful tuning is required to avoid fibroblast cytotoxicity [194-195]. Copper-containing hydrogels can completely eradicate high bacterial loads (e.g., 5×10^5 CFU mL^-1 of E. coli and S. aureus within 12 h in a reported gelatin methacrylate/adenine acrylate/Cu hydrogel) and are less costly than silver though oxidation and potential toxicity are concerns [197]. Zinc oxide nanorod-crosslinked carboxymethyl chitosan hydrogels provided slow Zn2+ release, synergistic antibacterial action, accelerated healing and reduced inflammation in animal models [198]. Metal-based composites are effective but require balancing ion release kinetics, antimicrobial potency and host cell compatibility.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 2
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::3:::0
| -728,056,911,412,881,900
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Antibiotic-loaded hydrogels: Antibiotics remain efficient when delivered locally to wounds. Hydrogels serve as reservoirs for antibiotics (vancomycin, gentamicin, ciprofloxacin, tobramycin) enabling local, sustained release and reduced systemic exposure. Strategies include incorporation into metal–organic frameworks for vancomycin delivery, electrostatic binding for pH-responsive gentamicin release lasting over weeks, and staged/encapsulated delivery of hydrophilic and hydrophobic antibiotics for programmed release [201-207]. Antibiotic-loaded hydrogels reduce required systemic doses but do not eliminate the risk of resistance if sub-inhibitory exposures occur; release profiles must therefore be carefully controlled. Antibacterial peptide–based composite hydrogels: Antimicrobial peptides (AMPs) are cationic, amphiphilic molecules that disrupt membranes and exhibit broad-spectrum activity with lower propensity for resistance. Examples include HHC-36 incorporated with cerium oxide nanoparticles into catechol-functionalized GelMA to yield >99% antibacterial activity while ceria scavenged ROS and supported healing [210]. pH-sensitive DP7 peptide/dextran hydrogels synergized with low-concentration antibiotics to kill resistant bacteria below conventional MICs, illustrating potential for synergistic, resistance-limiting therapies [211].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 3
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::3:::1
| 4,704,917,768,719,927,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Examples include HHC-36 incorporated with cerium oxide nanoparticles into catechol-functionalized GelMA to yield >99% antibacterial activity while ceria scavenged ROS and supported healing [210]. pH-sensitive DP7 peptide/dextran hydrogels synergized with low-concentration antibiotics to kill resistant bacteria below conventional MICs, illustrating potential for synergistic, resistance-limiting therapies [211]. Cost, proteolytic stability and potential immunogenicity are practical considerations for AMP-based dressings.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 3
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::4:::0
| 3,578,481,120,038,392,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
3) Stimulus-responsive antibacterial hydrogels
Photo-responsive hydrogels: Photothermal agents (PTAs) and photodynamic agents (PDAs) incorporated into hydrogels enable light-triggered antibacterial action. PTAs (graphene oxide, gold, CuS, black phosphorus) convert NIR light to heat to ablate bacteria, while PDAs (chlorin e6, porphyrins) produce singlet oxygen/ROS on illumination to oxidatively damage bacteria. Examples: catechol–Fe3+/gelatin/protocatechualdehyde hydrogels produced a temperature rise under NIR and achieved near-complete killing of Gram-negative and drug-resistant strains; dual-wavelength-activated CuS@MoS2-doped PVA hydrogels generated hyperthermia and ROS under 660 nm + 808 nm irradiation to rapidly kill bacteria via membrane permeabilization and GSH oxidation [103,236]. Photo-based approaches are highly effective at or near the skin surface but are limited by light penetration depth and require appropriate dosimetry to avoid host tissue damage.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 4
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::5:::0
| -5,091,508,305,803,046,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Acoustic (sonodynamic) responsive hydrogels: Ultrasound provides deeper tissue penetration and can activate sonosensitizers to produce ROS via sonoluminescence or cavitation. Hydrogels conjugating catalase with meso-tetra(4-carboxyphenyl)porphyrin (TCPP) to chitosan matrices produced ROS under sonication and enhanced antibacterial action while catalase helped modulate local oxygen levels to support sonodynamic efficacy [239]. Ultrasound can also trigger drug release by breaking labile bonds (e.g., borate esters) or enhancing diffusion. Electrical and other stimuli: Conductive hydrogels (polyaniline, polypyrrole composites) enable electrically stimulated antibacterial/repair processes: electrical stimulation can promote cell migration, angiogenesis and epithelialization while concurrently producing antibacterial effects and enabling electrically triggered drug release [247-251]. pH-responsive (Schiff base/imine) hydrogels release antibacterial agents in acidic infected microenvironments; thermo-responsive systems (poly(N-isopropylacrylamide)) and salt-responsive cationic peptide hydrogels have also been used to provide environment-driven antibacterial action [245-246].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 5
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::results::::::6:::0
| 1,970,976,102,218,467,000
|
Recent progress of antibacterial hydrogels in wound dressings — RESULTS
Representative dressing formats: hydrogels have been cast or fabricated into microneedle arrays (detachable, for programmed delivery), Janus patches (asymmetric inner/outer layers for combined local treatment and barrier protection), nanofiber-reinforced composites (improved toughness), injectable thermoresponsive gels, mussel-inspired adhesive hydrogels (catechol–Fe3+ chemistries), films/membranes (lightweight, high absorption), microsphere-based delivery systems, sponge-like porous hydrogels (high exudate uptake), and bandage-type hydrogels with hemostatic and adhesive functionality [122-129]. Each format is chosen to match wound type, depth, required mechanical properties, and desired release profile. Main antibacterial components (summary): natural polymers (chitosan, antibacterial cellulose derivatives, plant essential oils, lysozyme, antimicrobial peptides), synthetic antibacterial chemistries (N-halamines, quaternary ammonium salts, imidazolium derivatives, biguanides, phenols, nitriles) and inorganic agents (Ag, Cu, Zn, Mg, Au and their oxides) are the principal building blocks used to impart antibacterial function in hydrogels [143-188,212-221].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
results
| null | 6
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::discussion::::::0:::0
| 828,647,471,892,496,400
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
Synthesis of lessons and critical analysis
Crosslinking architecture and functional trade-offs: Permanent covalent hydrogels provide mechanical robustness and slow degradation, which is beneficial when long-term structural barrier function is needed; however, the limited polymer chain mobility reduces the contact area between matrix-bound antibacterial moieties and bacteria and limits rapid release-based responses. Dynamic covalent and physically crosslinked hydrogels provide enhanced chain mobility, self-healing, injectability, and rapid stimulus-responsiveness—attributes favorable for contact-based inherent antibacterial mechanisms and on-demand agent release—but often at the cost of reduced long-term mechanical stability. Hybrid networks that combine covalent backbones with reversible sacrificial bonds can be tuned to balance toughness, adhesiveness and responsiveness, and are therefore a widely adopted design choice for multifunctional wound dressings [89-103]. Antibacterial strategies: inherent antibacterial hydrogels (cationic polymers, antimicrobial peptides, phenolic compounds) minimize agent release and lower systemic exposure, which can reduce selection pressure for resistance. However, many inherent strategies rely on membrane disruption mediated by electrostatic interactions; as a result they can be less potent against high bacterial loads or biofilms compared with release-based strategies.
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
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discussion
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::discussion::::::0:::1
| -110,884,707,519,247,660
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
Antibacterial strategies: inherent antibacterial hydrogels (cationic polymers, antimicrobial peptides, phenolic compounds) minimize agent release and lower systemic exposure, which can reduce selection pressure for resistance. However, many inherent strategies rely on membrane disruption mediated by electrostatic interactions; as a result they can be less potent against high bacterial loads or biofilms compared with release-based strategies. Release-based hydrogels (metals, antibiotics, AMPs) provide higher immediate bactericidal activity and can be designed for sustained or triggered release, but they carry risks: metal ions can accumulate and be cytotoxic or impair wound healing at high concentrations, and antibiotics can promote resistance if released sub-therapeutically. Stimulus-responsive hydrogels combine the advantages of both approaches by enabling localized, temporally controlled activation—photothermal, photodynamic, sonodynamic and electrical modalities can provide high kill rates with reduced systemic exposure, but require compatible activation equipment and careful safety evaluation to avoid collateral tissue damage [234-244,247-251].
|
10.1016/j.mtbio.2023.100582
|
Recent progress of antibacterial hydrogels in wound dressings
|
discussion
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
|
10.1016/j.mtbio.2023.100582:::discussion::::::1:::0
| -7,846,682,583,003,011,000
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
Material safety and translational barriers: For clinical translation, cytocompatibility, hemocompatibility, controllable biodegradation and lack of harmful long-term residues are critical. Metals (Ag, Cu) and some synthetic antibacterial motifs have known dose-dependent cytotoxicity; therefore, release kinetics and total load must be optimized and validated in appropriate in vitro and in vivo models. Antimicrobial peptides are promising due to broad-spectrum activity and lower resistance propensity, but their cost, stability (proteolysis) and potential immunogenicity must be addressed. Regulatory pathways and sterilization procedures for composite and stimulus-responsive hydrogels are additional practical hurdles. Mechanical and functional matching to wound types: Mechanical properties reported in the literature span wide ranges depending on network strategy and reinforcement. Single networks can be suitable for low-load, superficial wounds, whereas DN, TN and multi-network hydrogels are better suited to mechanically demanding sites (joints, wounds subject to motion). Adhesive strength, burst pressure and lap-shear strength are important metrics for ensuring wound closure and preventing re-entry of pathogens; several reports document burst pressures in the tens to hundreds of mmHg and lap-shear strengths of tens of kPa in well-designed systems [56,59,62].
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Recent progress of antibacterial hydrogels in wound dressings
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discussion
| null | 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
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10.1016/j.mtbio.2023.100582:::discussion::::::1:::1
| -4,942,291,089,655,971,000
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
Single networks can be suitable for low-load, superficial wounds, whereas DN, TN and multi-network hydrogels are better suited to mechanically demanding sites (joints, wounds subject to motion). Adhesive strength, burst pressure and lap-shear strength are important metrics for ensuring wound closure and preventing re-entry of pathogens; several reports document burst pressures in the tens to hundreds of mmHg and lap-shear strengths of tens of kPa in well-designed systems [56,59,62]. Matching degradation rate to tissue regeneration kinetics—neither too fast to lose barrier function prematurely nor too slow to leave residues—is essential, especially for internal applications where surgical retrieval is impractical.
|
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Recent progress of antibacterial hydrogels in wound dressings
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discussion
| null | 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
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10.1016/j.mtbio.2023.100582:::discussion::::::2:::0
| 9,141,666,195,132,154,000
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
Recommended priorities for future research and development
1) Broader and standardized antibacterial testing: many studies test only S. aureus and E. coli. To better understand clinical relevance, researchers should test against a broader panel of clinically relevant pathogens (including P. aeruginosa, MRSA, Enterococcus spp., anaerobes) and biofilms, and should report both planktonic and biofilm efficacy, kill kinetics and minimum biofilm eradication concentrations. Standardized antibacterial assay conditions (inoculum size, exposure time, medium, presence of serum/exudate) will improve comparability. 2) Safety, degradation and long-term performance: systematic evaluation of cytotoxicity to keratinocytes, fibroblasts, endothelial cells, and immune cells, hemocompatibility, and in vivo biodistribution/clearance—especially for metal-containing and synthetic chemistries—is required. Studies should quantify degradation products and assess their biological activity. 3) Multifunctional, phase-adaptive systems: wounds progress through hemostasis, inflammation, proliferation and remodeling phases; single-mode dressings typically target one phase. Designing hydrogels that adapt their properties (adhesion, stiffness, pro-healing factor delivery, antimicrobial activity) over time or that respond to local biochemical cues (pH, ROS, enzymes) will better support staged healing.
|
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Recent progress of antibacterial hydrogels in wound dressings
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discussion
| null | 2
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
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10.1016/j.mtbio.2023.100582:::discussion::::::3:::0
| -2,680,449,133,484,764,000
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
4) Scalability, sterilization and regulatory considerations: robust synthetic routes, scalable fabrication (e.g., molding, printing, roll-to-roll processing), sterilization compatibility (gamma, ethylene oxide, autoclave where appropriate) and reproducible quality control are necessary for translation. The impact of sterilization on hydrogel chemistry and antibacterial efficacy should be characterized. 5) Integration with electronics and data-driven design: combining hydrogels with flexible electronics for on-demand stimulation (electrical/thermal), sensing (pH, temperature, biomarkers), and closed-loop feedback control may enable intelligent dressings. Machine learning and high-throughput screening can accelerate selection of polymer chemistries and crosslinking conditions to meet multi-parameter objectives. 6) Clinical study design: progress to clinically relevant large animal models and protocol-design for early-phase human trials is essential. Outcome measures should include infection rates, time to closure, functional outcomes, pain scores, dressing comfort and adverse events.
|
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Recent progress of antibacterial hydrogels in wound dressings
|
discussion
| null | 3
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
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10.1016/j.mtbio.2023.100582:::discussion::::::4:::0
| -4,718,526,084,499,116,000
|
Recent progress of antibacterial hydrogels in wound dressings — DISCUSSION
Limitations of current literature: many reports focus on proof-of-concept materials and short-term animal models; long-term safety, chronic wound models (e.g., diabetic wounds), realistic bacterial loads and biofilm challenges, and head-to-head comparisons with standard-of-care dressings are less common. Addressing these gaps will be crucial to determine the true translational potential of advanced antibacterial hydrogels.
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Recent progress of antibacterial hydrogels in wound dressings
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discussion
| null | 4
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
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10.1016/j.mtbio.2023.100582:::conclusion::::::0:::0
| 2,513,854,706,749,116,400
|
Recent progress of antibacterial hydrogels in wound dressings — CONCLUSION
Antibacterial hydrogels offer a versatile and powerful platform for wound management by combining physical protection, moisture balance and targeted antibacterial strategies. Crosslinking chemistry (permanent covalent, dynamic covalent, physical, and hybrid) is the principal design lever to tune mechanical performance, adhesiveness, responsiveness and release kinetics. Inherent antibacterial hydrogels (chitosan, antimicrobial peptides, quaternized polymers) minimize systemic exposure and resistance selection pressure but may require synergistic strategies for high bacterial loads or biofilms. Release-based hydrogels (metal ions, antibiotics, peptides) deliver potent bactericidal activity but demand careful control of dosing and biocompatibility. Stimulus-responsive systems (photothermal/photodynamic, sonodynamic, electrical, pH/thermal/salt-responsive) enable on-demand, localized antibacterial action with the potential to reduce resistance emergence. Hybrid network designs and multifunctional formats (microneedles, Janus patches, injectable scaffolds, adhesives) permit tailoring to wound type and clinical need. Future work must emphasize broader standardized antibacterial testing, rigorous safety and degradation studies, phase-adaptive multifunctionality, scalable manufacturing and sterilization, and integration with sensing/actuation and data-driven discovery to accelerate clinical translation.
|
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Recent progress of antibacterial hydrogels in wound dressings
|
conclusion
| null | 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1.3
|
10.1016/j.mtbio.2023.100582:::methods:::Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.:::0:::0
| 3,225,338,195,909,776,400
|
Recent progress of antibacterial hydrogels in wound dressings — METHODS / Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
1) Chemically crosslinked hydrogels
Chemically crosslinked hydrogels are built from covalent bonds. These can be permanent (irreversible) covalent crosslinks (providing durable, dimensionally stable networks) or dynamic covalent bonds (reversible covalent chemistry that enables exchange, self-healing, and stimuli responsiveness). Common covalent polymerization strategies used for wound dressings include free-radical polymerization, Schiff base formation (imine bonds), Michael addition, disulfide formation and cleavage, and Diels–Alder reactions [48-52]. Covalent crosslinking (permanent networks): single-network covalently crosslinked hydrogels provide robust networks but are often brittle and have limited fracture toughness. To overcome this, double-network (DN) or multi-network strategies use a combination of a rigid, sacrificial network and a ductile network to dissipate energy on deformation, significantly improving toughness and fracture resistance [53-56].
|
10.1016/j.mtbio.2023.100582
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Recent progress of antibacterial hydrogels in wound dressings
|
methods
|
Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
| 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 0.9
|
10.1016/j.mtbio.2023.100582:::methods:::Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.:::0:::1
| 6,558,515,183,228,225,000
|
Recent progress of antibacterial hydrogels in wound dressings — METHODS / Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
Covalent crosslinking (permanent networks): single-network covalently crosslinked hydrogels provide robust networks but are often brittle and have limited fracture toughness. To overcome this, double-network (DN) or multi-network strategies use a combination of a rigid, sacrificial network and a ductile network to dissipate energy on deformation, significantly improving toughness and fracture resistance [53-56]. Representative examples: a photo-crosslinked composite hydrogel using gelatin methacryloyl (GelMA), thioglycolic acid–modified chitosan (TCS) and polycaprolactone nanofibers modified with 3-buten-1-amine (PCLPBA) formed a covalent DN with improved mechanical behavior and antibacterial action from TCS [55]; a triple-network hydrogel based on chitosan (first network), amphoteric sulfopropyl betaine (PDMAPS, second network) and poly(2-hydroxyethyl acrylate) (PHEA, third network) achieved compressive stress ~81.9 MPa, tensile stress 384 kPa and fracture strain >1000% in one formulation [56].
|
10.1016/j.mtbio.2023.100582
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Recent progress of antibacterial hydrogels in wound dressings
|
methods
|
Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
| 0
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 0.9
|
10.1016/j.mtbio.2023.100582:::methods:::Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.:::1:::0
| -3,589,277,226,089,752,600
|
Recent progress of antibacterial hydrogels in wound dressings — METHODS / Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
Dynamic covalent crosslinking: dynamic covalent chemistries (Schiff base/imine bonds, boronate ester formation, disulfide bonds) confer reversible bond exchange, self-healing, injectability and responsiveness to environmental triggers (pH, glucose, reducing conditions). Examples include hydrogels formed by reaction of 2-formylphenylboronic acid with polyvinyl alcohol and 4-arm PEG derivatives to produce boronate/Schiff-base hybrid networks with on-demand dissolution and self-healing [66]; carboxymethyl chitosan/quercetin systems using boronate and Schiff-base interactions provided durable antibacterial hydrogels with activity against E. coli and S. aureus [67]. Dynamic covalent systems are particularly useful where reversible adhesion, injectability, and stimulus-responsive release are desirable [66-70]. 2) Physically crosslinked hydrogels
Physical crosslinks (electrostatic interactions, hydrogen bonding, hydrophobic association, π–π stacking, host–guest interactions and metal–ligand coordination) form networks without covalent bonds. These bonds are generally weaker and more dynamic than covalent bonds, enabling self-healing, rapid gelation, injectability and stimulus responsiveness.
|
10.1016/j.mtbio.2023.100582
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Recent progress of antibacterial hydrogels in wound dressings
|
methods
|
Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
| 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 0.9
|
10.1016/j.mtbio.2023.100582:::methods:::Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.:::1:::1
| -8,577,680,980,965,900,000
|
Recent progress of antibacterial hydrogels in wound dressings — METHODS / Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
2) Physically crosslinked hydrogels
Physical crosslinks (electrostatic interactions, hydrogen bonding, hydrophobic association, π–π stacking, host–guest interactions and metal–ligand coordination) form networks without covalent bonds. These bonds are generally weaker and more dynamic than covalent bonds, enabling self-healing, rapid gelation, injectability and stimulus responsiveness. For instance, hydrogels assembled through hydrogen bonding and catechol–Fe3+ coordination can show rapid self-healing combined with tissue adhesion; self-assembled peptide hydrogels based on π–π stacking and hydrogen bonding can entangle into nanofiber networks that strongly inhibit bacterial growth owing to the presence of antimicrobial peptides [71-74]. A peptide-based hydrogel formed by hydrophobic assembly of the natural antimicrobial peptide Jelleine-1 in the presence of 8-bromoadenosine 3',5'-cyclic monophosphate self-assembled into a nanofiber network that eradicated bacterial colonies rapidly and promoted wound healing via upregulation of TGF-β and VEGF in vivo [72]. Physically crosslinked hydrogels are preferable when rapid responsiveness or minimal exogenous chemistry is desired.
|
10.1016/j.mtbio.2023.100582
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Recent progress of antibacterial hydrogels in wound dressings
|
methods
|
Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
| 1
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 0.9
|
10.1016/j.mtbio.2023.100582:::methods:::Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.:::2:::0
| 2,295,385,456,866,528,500
|
Recent progress of antibacterial hydrogels in wound dressings — METHODS / Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
3) Hybrid crosslinked hydrogels
Hybrid networks combine covalent bonds with reversible physical interactions so that a permanent covalent backbone provides structural integrity while dynamic physical bonds dissipate energy and provide self-healing and responsiveness. Examples include silk fibroin hydrogels physically crosslinked by Ga3+ coordination and covalent networks formed by hemoglobin-catalyzed crosslinking; the Ga3+ served both as a physical crosslinker and as an antibacterial agent while hemoglobin-mediated crosslinking improved mechanical performance and oxygen delivery for diabetic wounds [101]. Other hybrid formulations combine Schiff-base chemistry with hydrogen bonding or metal coordination to achieve balanced mechanical strength, adhesion and stimulus-responsive antibacterial activity [79,85,88]. Summary of common crosslinking methods and their functional characteristics: (a) permanent covalent crosslinking (radical polymerization, enzymatic crosslinking) yields high strength and durability but limited chain mobility; (b) dynamic covalent crosslinking (Schiff base, boronate ester, disulfide) enables self-healing, injectability and stimulus-responsive behavior; (c) physical crosslinking (ionic coordination, hydrogen bonding, electrostatic attraction, hydrophobic association, host–guest) imparts rapid gelation and reversibility; (d) hybrid strategies combine the advantages of the above and are widely used for multifunctional wound dressings [59-88].
|
10.1016/j.mtbio.2023.100582
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Recent progress of antibacterial hydrogels in wound dressings
|
methods
|
Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
| 2
|
["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 0.9
|
10.1016/j.mtbio.2023.100582:::methods:::Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.:::3:::0
| 6,779,314,185,957,410,000
|
Recent progress of antibacterial hydrogels in wound dressings — METHODS / Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
Mechanical property trends linked to crosslinking architecture: studies comparing single-network (SN), double-network (DN) and triple- or multi-network (TN/MN) hydrogels consistently show large improvements in compressive and tensile strength and toughness when additional sacrificial networks are introduced. Reported examples include: an SN with compression strength ~17 kPa and modulus ~35 kPa versus a DN with compression strength ~985 kPa and modulus ~1.14 MPa [59]; SN fracture/compression forces ~17.6 N/~18 N versus DN ~30.3 N/~25 N in a carrageenan-based system [58]; increases in tensile strength from ~100 kPa (SN) to ~400 kPa (DN) and compression strength from ~100 kPa to ~230 kPa upon formation of additional networks [60]. Multi-network systems combining chitosan with zwitterionic and neutral polymer networks exhibited compressive stresses up to tens of MPa in some formulations, reflecting the potential for very high mechanical performance when networks are carefully designed [56]. These mechanical gains are frequently leveraged when dressings must withstand motion and mechanical load while maintaining barrier and antibacterial function.
|
10.1016/j.mtbio.2023.100582
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Recent progress of antibacterial hydrogels in wound dressings
|
methods
|
Overview: the fabrication method and crosslinking chemistry of a hydrogel determine its basic wound-dressing performance: adhesion, mechanical strength and toughness, swelling behavior, hemostatic capability, degradation rate, and capacity for drug loading and controlled release [44-47]. Designing antibacterial hydrogel wound dressings therefore begins with selecting appropriate raw materials and crosslinking strategies to obtain the target mechanical and functional profile for the intended wound environment.
| 3
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["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 0.9
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10.1016/j.mtbio.2023.100582:::supplementary::::::0:::0
| -9,207,135,480,966,198,000
|
Recent progress of antibacterial hydrogels in wound dressings — SUPPLEMENTARY
The original manuscript referenced supplementary figures/tables that were not included in the source provided; these are indicated in the text where appropriate (not included in this document). Researchers interested in the primary data and supporting images/tables should consult the original publications cited in this review for experimental details, full datasets, and image materials (references cited throughout: [55-267]).
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Recent progress of antibacterial hydrogels in wound dressings
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supplementary
| null | 0
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["Antibacterial hydrogels", "Wound dressings", "Preparation methods", "Antibacterial strategies", "Applications"]
| 1
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10.1016/j.biotno.2022.07.002:::title::::::0:::0
| 3,608,978,084,385,519,000
|
Synthetic biology landscape in the UK — TITLE
Synthetic biology landscape in the UK
|
10.1016/j.biotno.2022.07.002
|
Synthetic biology landscape in the UK
|
title
| null | 0
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::abstract::::::0:::0
| 8,310,654,753,162,074,000
|
Synthetic biology landscape in the UK — ABSTRACT
The United Kingdom hosts a diverse and active synthetic biology community spanning academic research centres, student societies, accelerators, incubators, genome foundries and government policy bodies. This review maps the organisations and networks that underpin the UK ecosystem, traces the historical development of the community from seminal engineering-biology papers and the rise of iGEM to national roadmaps and research centres, and describes mechanisms that support translation and commercialisation (accelerators, venture funds, foundries, and academic technology‑transfer pathways). We summarise the UK's position in the global bioeconomy and compare aspects of translational practice with the United States—notably differences in patenting and spin‑out equity models—and identify enabling infrastructure, financial incentives and cultural barriers that influence founder outcomes. The UK exhibits strengths in scientific output, a growing entrepreneur‑focused student and early‑career community, and expanding translation infrastructure. Continued emphasis on founder-friendly technology transfer, investment in throughput and manufacturing capacity, protection and management of early‑stage IP, and sustained training will be important to consolidate and accelerate the UK’s leadership in engineering biology.
|
10.1016/j.biotno.2022.07.002
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Synthetic biology landscape in the UK
|
abstract
| null | 0
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1.3
|
10.1016/j.biotno.2022.07.002:::introduction::::::0:::0
| 1,575,736,195,379,516,700
|
Synthetic biology landscape in the UK — INTRODUCTION
Background and aims
Synthetic biology has matured over the past two decades from a nascent discipline into a broad engineering approach to biology. Two widely cited early studies from 2000—the genetic "Toggle Switch" and the "Repressilator"—framed the ambition to design predictable, reusable biological parts and circuits [1,2]. Those conceptual advances stimulated community formation through the international Genetically Engineered Machine competition (iGEM) and the first international synthetic biology meeting (SB1.0) at MIT in 2004 [8]. Since then, global hubs have formed to support education, knowledge exchange and technology translation; the UK has been an early and active participant in these developments. Scope of this review
This paper provides a cleared and structured overview of the UK synthetic‑biology landscape: the historical development of the community, the academic and student organisations that sustain training and talent, the translational infrastructure that supports spin‑outs and scale‑up, the government and funding landscape that shapes the bioeconomy, and policy and technology‑transfer practices that affect commercialisation. Where relevant the review contrasts UK features with those of the US to highlight differences in translation outcomes [6,7]. All inline citations are preserved in their original numeric form.
|
10.1016/j.biotno.2022.07.002
|
Synthetic biology landscape in the UK
|
introduction
| null | 0
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::introduction::::::1:::0
| 5,714,606,642,389,744,000
|
Synthetic biology landscape in the UK — INTRODUCTION
History and community formation
Early UK engagement with the emerging synthetic‑biology community began in the mid‑2000s. The University of Cambridge fielded one of the first international iGEM teams (2005) and Imperial College London placed runner‑up in 2006 [9,10]. National investment and coordination followed: the Centre for Synthetic Biology at Imperial College was established in 2008 (reported initial investment ~£8 million), and seven national research networks received approximately £970,000 in combined funding to address technological and societal aspects of synthetic biology [3]. In 2012 the UK Synthetic Biology Roadmap was published by the Synthetic Biology Leadership Council (SBLC), setting out priorities that included translational research and infrastructure [11]. Academic, research and student infrastructure
A dense network of research centres has emerged across the UK and researchers commonly move between these centres. Major centres and initiatives include the Centre for Synthetic Biology at Imperial College London, OpenPlant Cambridge, the Warwick Integrative Synthetic Biology Centre (WISB), BrisSynBio (a BBSRC/EPSRC‑funded Synthetic Biology Research Centre), the UK Centre for Mammalian Synthetic Biology (SynthSys, University of Edinburgh), the Synthetic Biology Research Centre Nottingham and SYNBIOCHEM at the University of Manchester. Research councils (principally BBSRC and EPSRC) have supported networks and centres that act as hubs for both fundamental research and translational activity [3].
|
10.1016/j.biotno.2022.07.002
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Synthetic biology landscape in the UK
|
introduction
| null | 1
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["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
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10.1016/j.biotno.2022.07.002:::introduction::::::2:::0
| -6,895,489,717,816,545,000
|
Synthetic biology landscape in the UK — INTRODUCTION
Student societies and the next generation of founders
Student‑founded societies are an important part of the UK ecosystem and often originate from iGEM teams or alumni networks. Examples include SynBio Imperial College, UCL BeakerSoc, the SynBio Society at the University of Edinburgh, and the Oxford University Biotech Society. Doctoral training centres such as BioDesign Engineering CDT contribute to multidisciplinary training. SynBioUK was founded in 2017 by PhD students at the University of Oxford to provide national coordination of student activities; it initially focused on undergraduate iGEM meetups and panels and shifted in 2020 toward graduate training and entrepreneurship through the Catalyse programme. Within two years Catalyse grew to ~300 participants and produced more than 20 teams, several of which spun out as startups. From 2022 SynBioUK leadership partnered with Nucleate (a student‑led accelerator that began in the US) to expand founder‑first accelerator activity in London, Oxford and Cambridge; Nucleate’s partnership with the Petri fund includes an offering of USD 1.5 million in uncapped, non‑discounted SAFE notes to selected teams.
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10.1016/j.biotno.2022.07.002
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Synthetic biology landscape in the UK
|
introduction
| null | 2
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["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
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10.1016/j.biotno.2022.07.002:::introduction::::::3:::0
| -2,342,012,438,371,934,000
|
Synthetic biology landscape in the UK — INTRODUCTION
Translation infrastructure: accelerators, incubators, independent labs and foundries
Translation in the UK is supported by a mix of global and local accelerators, dedicated biotech venture funds, academic commercialisation hubs, independent lab spaces and genome foundries. Examples of accelerators and programmes that have supported UK teams include Nucleate, Entrepreneur First, Conception X and GapSummit; biotech‑focused venture funds mentioned in the community include Petri, NfX Bio and Nucleus Capital. Academic commercialisation and incubation support is provided by units such as SynBiCITE (Imperial College), university incubators like the Imperial White City incubator, the Oxford BioEscalator and Cambridge Start Codon, and independent rentable labs including OpenCell (BioHotel), Scale Space and BioCity (Nottingham & Glasgow). These independent and university‑run spaces provide combinations of wet labs, offices and business support that reduce the capital required to start a company and make a "fail‑fast" approach more practicable in biotech.
|
10.1016/j.biotno.2022.07.002
|
Synthetic biology landscape in the UK
|
introduction
| null | 3
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
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| -8,200,853,020,842,026,000
|
Synthetic biology landscape in the UK — INTRODUCTION
Major UK genome foundries and distributed capabilities
There are multiple high‑throughput foundries in the UK that provide services such as DNA synthesis, strain engineering and automated workflows. The principal foundries and their locations noted in the survey are: Edinburgh Genome Foundry (Edinburgh), the Industrial Biotechnology Innovation Centre (IBioIC) facilities (Glasgow), the SynBiCITE London DNA Foundry (London), the Earlham Biofoundry (Norwich) and the SYNBIOCHEM Biofoundry (Manchester). These foundries expand the ability of academic and commercial teams to carry out design–build–test cycles at scale and act as shared infrastructure for translational projects. Acronyms and coordination bodies
Multiple government, funding and coordination bodies shape the UK landscape. Government departments and research funders referenced include BEIS (Business, Energy and Industrial Strategy), other government departments (OGDs), BBSRC (Biotechnology and Biological Sciences Research Council), Innovate UK (I‑UK) and the Knowledge Transfer Network (KTN). Industry coordination and leadership forums referenced include the Industrial Biotechnology Leadership Forum (IBLF), the Medicines Manufacturing Industry Partnership (MMIP), the Synthetic Biology Leadership Council (SBLC) and its successor the Engineering Biology Leadership Council (EBLC). These bodies work with industry and academia to develop strategies and roadmaps for the UK bioeconomy.
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Synthetic biology landscape in the UK
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introduction
| null | 4
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::introduction::::::5:::0
| -8,439,403,624,866,478,000
|
Synthetic biology landscape in the UK — INTRODUCTION
The UK's bioeconomy, funding and policy context
The UK government has identified biotechnology and related areas as national priorities for economic growth, food security, health and sustainability, and has set ambitions to expand the bioeconomy (for example, stated aims to grow the bioeconomy by 2030) [14,18]. In terms of scientific output the UK leads in Europe: between 2000 and 2015 the UK contributed approximately 10.1% of synthetic‑biology publications, and between 2016 and 2020 it achieved the third‑greatest global publication impact after the US and China [6,19]. However, the UK files fewer patents relative to its scientific output and to the resources it receives [7]. Public and private funding landscape
Private investment in UK biotech principally comes from venture capital and angel investors; in recent years venture funding has increased substantially with total life‑sciences investment in 2021 reported at approximately £4.5 billion and venture investment in biotech contributing a significant portion of that [27,28]. While VC teams with scientific backgrounds are increasingly based in both the US and the UK, many UK founders still seek US investors during funding rounds.
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10.1016/j.biotno.2022.07.002
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Synthetic biology landscape in the UK
|
introduction
| null | 5
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::introduction::::::6:::0
| -1,594,224,729,991,305,200
|
Synthetic biology landscape in the UK — INTRODUCTION
To bridge early funding gaps the UK has established a range of public‑sector funds and support programmes. Examples include Catapult centres (Innovate UK Catapult Network), Innovation to Commercialisation of University Research (ICURE), university and student competitions (for example YES) and hackathons (for example the University of Sheffield Biodigester Hackathon) [20]. The UK Innovation and Science Seed (UKI2S) Fund received a £10 million investment to establish a Synthetic Biology Seed Fund [29], and the Industrial Biotechnology Catalyst has provided funding totalling over £76 million for biomanufacturing projects [30]. Translational funding from research councils to synthetic‑biology centres also serves as seed funding for spin‑outs and proof‑of‑concept work [31]. Policy framing: from "synthetic biology" to "engineering biology"
Nomenclature in policy has shifted over time: while the term "synthetic biology" appeared in the 2015 list of "eight great technologies," by 2017 the UK government and many associated bodies increasingly used the term "engineering biology" (for example the Engineering Biology Leadership Council) [32,33]. This re‑framing reflects policy and industrial engagement with the engineering and translation aspects of the field.
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Synthetic biology landscape in the UK
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introduction
| null | 6
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["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
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10.1016/j.biotno.2022.07.002:::introduction::::::7:::0
| -6,444,771,491,487,274,000
|
Synthetic biology landscape in the UK — INTRODUCTION
Intellectual property and tax incentives
The UK offers tax incentives to encourage private investment: Enterprise Investment Scheme (EIS), Seed Enterprise Investment Scheme (SEIS), Social Investment Tax Relief (SITR) and Venture Capital Trusts (VCTs). For example, SEIS supports smaller businesses by capping the amount of capital eligible for relief (currently £100,000) and offering up to 50% income tax relief on qualifying investments [34]. Such incentives support angel investment at stages where public and VC funding may be limited. Comparisons with the United States
Although UK research productivity (publications) is strong on a per‑GDP basis, the United States remains dominant in technology translation and patenting. One metric reported for comparison indicates the US averages roughly 54 patents per 1,000 publications while the UK averages about 8 patents per 1,000 publications, highlighting a gap in converting scientific output to protected technology and commercial opportunities.
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Synthetic biology landscape in the UK
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introduction
| null | 7
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["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::discussion::::::0:::0
| -8,216,854,767,737,320,000
|
Synthetic biology landscape in the UK — DISCUSSION
Strengths of the UK ecosystem
The UK synthetic‑biology ecosystem combines a strong academic base, a dense set of research centres, an active student and early‑career community and diverse translation pathways (incubators, accelerators, foundries and venture capital). These elements create an environment that is relatively founder‑friendly compared with many other jurisdictions: company formation is straightforward, public tax incentives encourage early investors, and an expanding network of affordable shared labs and incubators reduces the initial capital requirement for wet‑lab ventures. Technology transfer, institutional equity and founder incentives
A persistent challenge for founders has been the historic structure of technology transfer agreements and institutional equity stakes in spin‑outs. Many UK universities historically retained 20–50% equity in spin‑out companies, a level that can deter founders and complicate venture financing by reducing the equity available to investors. By contrast, prominent US entrepreneurship institutions (for example MIT and Stanford) frequently pursue licensing approaches that take little or no permanent equity, which can leave founders better positioned to attract investment and scale companies.
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Synthetic biology landscape in the UK
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discussion
| null | 0
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::discussion::::::1:::0
| 7,715,787,097,552,696,000
|
Synthetic biology landscape in the UK — DISCUSSION
Recent UK changes to equity models and licensing
In the last five years several UK universities have introduced more founder‑friendly models. Imperial College introduced a founder‑driven route in 2017 that permitted founders to retain up to 95% of company equity during an 18‑month pilot; the founder‑driven route became a permanent option after most participants preferred it to a co‑driven route in which the institution retained around 50% equity [35]. The University of Oxford revised its approach in 2021 to typically allow founders to retain approximately 80% equity, with institutional involvement and stake levels tied to the degree and nature of institutional support. These shifts in technology‑transfer practice have improved founders’ negotiating positions, increased access to follow‑on investment and made the UK comparatively more attractive for spin‑out formation.
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Synthetic biology landscape in the UK
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discussion
| null | 1
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::discussion::::::2:::0
| 7,412,993,321,971,089,000
|
Synthetic biology landscape in the UK — DISCUSSION
Outstanding barriers and recommendations
Despite improvements, several barriers remain:
- Patenting and IP culture: The UK patents fewer inventions per unit of scientific output than the US. Strengthening IP management practices, earlier support for idea protection and clearer commercial pathways can increase conversion of research into protected technologies. - Access to scale and manufacturing: Medium‑stage companies require capital‑intensive manufacturing and scale‑up capabilities. Continued investment in throughput facilities, biomanufacturing testbeds and pilot plants is critical to demonstrate economic viability for bio‑based processes and to enable access to industry sectors that are currently uneconomical at lab scale. - Talent and international competitiveness: Attracting top international talent and inward investment requires competitive training programs, international exchange opportunities and support for immigration‑era policies that facilitate mobility of skilled scientists and entrepreneur‑founders. - Cultural change in universities: A broader cultural shift to value and protect early ideas, offer transparent and founder‑friendly licensing, and provide business training for academic teams will help bridge gaps between research and commercialisation.
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Synthetic biology landscape in the UK
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discussion
| null | 2
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::discussion::::::3:::0
| -5,458,662,296,901,726,000
|
Synthetic biology landscape in the UK — DISCUSSION
Policy framing and the future of "engineering biology"
The renaming of synthetic biology to "engineering biology" in many policy documents reflects a deliberate emphasis on engineering principles and industrial translation. This framing aligns government priorities with infrastructure investment (foundries, Catapult centres, pilot plants) and translational funding (innovation challenges, seed funds). Maintaining that focus while ensuring support for discovery research will be important to preserve the UK’s scientific leadership while accelerating industrial impact. Comparison with the United States and global outlook
The US remains the world leader in translating synthetic biology into companies and patented technologies, aided by large private capital pools, an entrepreneurial culture, flexible technology‑transfer practices at leading universities and an extensive industrial base. The UK’s comparative advantages are strong scientific output, concentrated research hubs, an active student founder pipeline and evolving, founder‑friendly technology‑transfer practices. To close remaining gaps with the US, the UK should continue to encourage patenting where appropriate, nurture founder equity and licensing models that allow startups to access follow‑on capital, and invest in manufacturing and scale‑up infrastructure. These steps will improve the likelihood that UK discoveries progress to commercially viable, scaled products and processes.
|
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Synthetic biology landscape in the UK
|
discussion
| null | 3
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1
|
10.1016/j.biotno.2022.07.002:::conclusion::::::0:::0
| 2,158,876,731,787,504,600
|
Synthetic biology landscape in the UK — CONCLUSION
Summary and outlook
The UK synthetic‑biology community is vibrant, diverse and increasingly well connected across universities, student societies, research centres, accelerators, foundries and government advisory bodies. Strengths include strong scientific output, an expanding early‑career and student entrepreneur network, improving technology‑transfer policies that are becoming more founder‑friendly, and a growing set of translational infrastructures such as foundries and incubators. Key priorities going forward
To consolidate and expand its leadership in engineering biology, the UK should prioritize:
- Continued funding for training, doctoral programmes and research centres that generate technical and entrepreneurial talent. - Policies and institutional norms that protect and commercialise early ideas while enabling founders to retain sufficient equity to attract investors. - Investment in manufacturing throughput capacity, pilot plants and bioprocess testbeds to allow rigorous de‑risking and scale‑up of processes. - Strengthening IP management and incentives to increase patenting where it supports commercial development. - International exchange and talent attraction programmes to broaden experience, networks and capital access.
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Synthetic biology landscape in the UK
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conclusion
| null | 0
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1.3
|
10.1016/j.biotno.2022.07.002:::conclusion::::::1:::0
| 3,654,808,249,988,349,400
|
Synthetic biology landscape in the UK — CONCLUSION
With coordinated public‑private investment, a continued cultural shift toward supporting founder autonomy, and sustained emphasis on scale‑up capacity, the UK is well positioned to translate its scientific strengths into a globally competitive engineering‑biology industry.
|
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Synthetic biology landscape in the UK
|
conclusion
| null | 1
|
["synthetic biology", "engineering biology", "bioeconomy", "technology translation", "foundries", "UK"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::title::::::0:::0
| -6,782,837,238,993,345,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — TITLE
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
title
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::abstract::::::0:::0
| -7,035,138,714,314,776,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — ABSTRACT
Intervertebral disc degeneration (IVDD) is a leading cause of spinal disability. The inflammatory microenvironment within the avascular disc is central to IVDD progression, driving extracellular matrix (ECM) catabolism, cell apoptosis, neurotrophin production, and pain. Conventional systemic anti-inflammatory therapies (glucocorticoids, NSAIDs, biologics) are limited by short local residence, systemic adverse effects, or poor penetration into the disc. Biomaterial-based delivery platforms — including nanoparticles, liposomes, nanomicelles, nanozymes, microspheres, hydrogels, electrospun fibers, and composite scaffolds — are being developed to locally and sustainably modulate inflammation while protecting labile cargos (small molecules, proteins, nucleic acids, cells, and extracellular vesicles). This narrative review synthesizes (1) IVD anatomy and the pathophysiologic role of inflammation in IVDD, (2) anti-inflammatory pharmacologic, biologic, gene- and cell-based therapeutics being evaluated for IVDD, and (3) biomaterial carriers and their performance in preclinical models.
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10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
abstract
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::abstract::::::0:::1
| 5,749,031,182,929,034,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — ABSTRACT
Biomaterial-based delivery platforms — including nanoparticles, liposomes, nanomicelles, nanozymes, microspheres, hydrogels, electrospun fibers, and composite scaffolds — are being developed to locally and sustainably modulate inflammation while protecting labile cargos (small molecules, proteins, nucleic acids, cells, and extracellular vesicles). This narrative review synthesizes (1) IVD anatomy and the pathophysiologic role of inflammation in IVDD, (2) anti-inflammatory pharmacologic, biologic, gene- and cell-based therapeutics being evaluated for IVDD, and (3) biomaterial carriers and their performance in preclinical models. We summarize representative material systems and cargo combinations, highlight mechanisms of action (e.g., NF-κB/MAPK inhibition, ROS scavenging, macrophage M1→M2 polarization, senescent cell clearance, gene silencing), and discuss strengths, limitations, and translational challenges. Multifunctional, stimuli-responsive biomaterials that combine anti-inflammatory, antioxidative and pro-regenerative cues with sustained, targeted release show the greatest promise to restore disc homeostasis and promote regeneration.
|
10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
abstract
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::introduction::::::0:::0
| 7,978,802,441,703,527,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — INTRODUCTION
Background and normal structure. The intervertebral disc (IVD) is a hydrated fibrocartilaginous organ situated between vertebral bodies and consists of three principal components: the central nucleus pulposus (NP), the surrounding annulus fibrosus (AF), and the cartilaginous endplates (CEPs) [10]. The NP is a gelatinous, highly hydrated core (approximately 80–90% water in the normal adult) rich in proteoglycans and type II collagen that distributes compressive loads to the AF. The AF is organized into 15–25 concentric lamellae; the inner AF contains a mixture of type I and type II collagen while the outer AF is dominated by type I collagen and confers tensile strength [11,12]. CEPs separate the disc from vertebral bone, are thin (~1 mm average), and contain porous microstructures that allow limited nutrient diffusion to the avascular NP [13,14]. After development the disc becomes largely avascular and isolated from systemic circulation, creating a closed microenvironment [15].
|
10.1016/j.bioactmat.2023.11.021
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
introduction
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::introduction::::::1:::0
| -5,273,895,142,422,318,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — INTRODUCTION
Pathophysiology and role of inflammation in IVDD. Degeneration typically begins in the NP with proteoglycan degradation and loss of water-retaining notochordal cells, causing decreased NP hydration and altered biomechanics [16–18]. Collagen composition shifts (decreased type II, increased type I), the ECM and elastic network become disordered, and AF microtrauma and fissures develop. AF breaches expose NP antigens to the immune system, which may trigger autoimmune and persistent inflammatory responses [19,20]. Immune cell infiltration (macrophages, T cells, B cells), innate sensing, and resident cell secretion together create an inflammatory milieu characterized by elevated cytokines (TNF-α, IL-1α/β, IL-6, IFN-γ), chemokines, prostaglandin E2, and proteolytic enzymes (MMPs, ADAMTS) [21–31]. IL-1β and TNF-α activate NF-κB and MAPK signaling, upregulate catabolic enzymes (MMP1, MMP3, MMP9, MMP10, ADAMTS4), inhibit ECM synthesis, and promote NP cell apoptosis and catabolism [41–44].
|
10.1016/j.bioactmat.2023.11.021
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
introduction
| null | 1
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::introduction::::::1:::1
| 5,747,534,310,872,599,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — INTRODUCTION
Immune cell infiltration (macrophages, T cells, B cells), innate sensing, and resident cell secretion together create an inflammatory milieu characterized by elevated cytokines (TNF-α, IL-1α/β, IL-6, IFN-γ), chemokines, prostaglandin E2, and proteolytic enzymes (MMPs, ADAMTS) [21–31]. IL-1β and TNF-α activate NF-κB and MAPK signaling, upregulate catabolic enzymes (MMP1, MMP3, MMP9, MMP10, ADAMTS4), inhibit ECM synthesis, and promote NP cell apoptosis and catabolism [41–44]. Sustained inflammation is amplified by macrophage polarization to an M1 phenotype, recruitment of additional immune cells, and the senescence-associated secretory phenotype (SASP) in aged cells that releases proinflammatory mediators [28,29,45,46]. Important signaling pathways implicated in IVDD include NF-κB, p38 MAPK, Wnt/β-catenin, TGF-β/BMP, and others that modulate ECM homeostasis, inflammation, and cell survival [47–54].
|
10.1016/j.bioactmat.2023.11.021
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
introduction
| null | 1
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::introduction::::::2:::0
| 9,133,510,519,195,473,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — INTRODUCTION
Clinical problem and rationale for biomaterials. Conservative management (analgesics, physical therapy) often fails to halt degeneration and surgery can be invasive and biomechanically disruptive [5]. The avascular nature of the NP limits systemic drug delivery, making local intradiscal administration the preferred route for modulating disc pathology [1,7]. However, direct injection of small molecules, proteins, or nucleic acids into the disc is frequently limited by short residence time, rapid diffusion/clearance, poor stability, and the hostile biochemical microenvironment (low oxygen, acidity, oxidative stress). Biomaterial platforms capable of local, sustained, and stimuli-responsive delivery that also provide mechanical support and microenvironmental modulation are therefore promising for disease modification and regeneration [8,9]. Schematic summary (replaces Figure 1). A conceptual schematic summarizes how NP and AF degeneration results in release of inflammatory mediators (TNF-α, IL-1β, IL-6), activation of NF-κB and MAPK pathways, upregulation of matrix-degrading enzymes (MMPs, ADAMTS), immune cell recruitment (macrophages, T cells, B cells), macrophage polarization to M1 phenotype, NP cell apoptosis, ECM loss, and pain generation. These processes form feed-forward loops that sustain and expand degeneration.
|
10.1016/j.bioactmat.2023.11.021
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
introduction
| null | 2
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::results::::::0:::0
| 1,617,599,141,008,842,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Overview. Multiple classes of anti-inflammatory interventions have been explored for IVDD: small-molecule drugs (glucocorticoids, NSAIDs), natural products and traditional medicines, biologics (cytokine antagonists, monoclonal antibodies), gene therapies (plasmid, mRNA, siRNA/miRNA), cell-based approaches (MSCs, NP-like cells), and cell-derived products (exosomes, PRP). Biomaterial carriers — natural polymers (HA, collagen/gelatin, chitosan, alginate, silk fibroin), synthetic polymers (PLA/PLGA, PCL, PEA, PVA, pNIPAAm, polyurethane), nanosystems (nanoparticles, liposomes, nanomicelles, nanozymes), microspheres, injectable hydrogels, and electrospun scaffolds — have been combined with these cargos to extend retention, protect labile agents, enable stimuli-responsive release, and provide structural support. 1) Pharmacologic and natural anti-inflammatory agents (synthesized summary of Table 1).
|
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
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results
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::0:::1
| -7,091,839,703,082,723,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Biomaterial carriers — natural polymers (HA, collagen/gelatin, chitosan, alginate, silk fibroin), synthetic polymers (PLA/PLGA, PCL, PEA, PVA, pNIPAAm, polyurethane), nanosystems (nanoparticles, liposomes, nanomicelles, nanozymes), microspheres, injectable hydrogels, and electrospun scaffolds — have been combined with these cargos to extend retention, protect labile agents, enable stimuli-responsive release, and provide structural support. 1) Pharmacologic and natural anti-inflammatory agents (synthesized summary of Table 1). - Glucocorticoids: GCs inhibit phospholipase A2, suppress NF-κB and AP-1 activity, and modulate p38 MAPK signaling and macrophage cytokine production, reducing leukotriene and prostaglandin synthesis and attenuating neural sensitization [56,59,60]. Epidural or local injections can reduce inflammatory cell activity and cytokine expression in degenerated discs, but systemic side effects (adrenal suppression, hypertension, hyperglycemia, osteoporosis, infection risk) limit long-term use; local delivery minimizes systemic exposure [61–68].
|
10.1016/j.bioactmat.2023.11.021
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
results
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::0:::2
| -8,797,372,723,061,530,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- Glucocorticoids: GCs inhibit phospholipase A2, suppress NF-κB and AP-1 activity, and modulate p38 MAPK signaling and macrophage cytokine production, reducing leukotriene and prostaglandin synthesis and attenuating neural sensitization [56,59,60]. Epidural or local injections can reduce inflammatory cell activity and cytokine expression in degenerated discs, but systemic side effects (adrenal suppression, hypertension, hyperglycemia, osteoporosis, infection risk) limit long-term use; local delivery minimizes systemic exposure [61–68]. - NSAIDs: NSAIDs inhibit cyclooxygenase enzymes, lowering prostaglandin production and pain signaling [57,69]. Aspirin and other NSAIDs downregulate MMP-3, MMP-13, iNOS, COX-2, IL-1β, and TNF-α in vitro and in animal models, suggesting potential to suppress disc inflammation and catabolism [70]. Selective COX-2 inhibitors (e.g., celecoxib) can reduce PGE2, MMP-13, and ADAMTS-5 while preserving type II collagen and proteoglycans and may activate autophagy via mTOR inhibition to protect NP cells from apoptosis [71–74].
|
10.1016/j.bioactmat.2023.11.021
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Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
results
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::0:::3
| 1,959,893,843,934,753,500
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Aspirin and other NSAIDs downregulate MMP-3, MMP-13, iNOS, COX-2, IL-1β, and TNF-α in vitro and in animal models, suggesting potential to suppress disc inflammation and catabolism [70]. Selective COX-2 inhibitors (e.g., celecoxib) can reduce PGE2, MMP-13, and ADAMTS-5 while preserving type II collagen and proteoglycans and may activate autophagy via mTOR inhibition to protect NP cells from apoptosis [71–74]. NSAIDs are primarily symptomatic treatments and are insufficient alone to regenerate advanced disc degeneration. - Natural products and traditional medicines: Plant- and microbe-derived compounds provide a large pool of anti-inflammatory candidates with relatively favorable safety. Curcumin inhibits TNF-α/IL-1β, NF-κB, and COX-2 and reduces oxidative stress, but has poor solubility and bioavailability requiring carrier systems [75,76]. Ferulic acid suppresses NF-κB activation and downstream COX-2, iNOS, and adhesion molecules, and protects against IL-1β-induced degeneration via Sirt1/AMPK/PGC-1α signaling [77–80].
|
10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
results
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::0:::4
| -6,517,590,748,413,254,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Curcumin inhibits TNF-α/IL-1β, NF-κB, and COX-2 and reduces oxidative stress, but has poor solubility and bioavailability requiring carrier systems [75,76]. Ferulic acid suppresses NF-κB activation and downstream COX-2, iNOS, and adhesion molecules, and protects against IL-1β-induced degeneration via Sirt1/AMPK/PGC-1α signaling [77–80]. Genipin has crosslinking and anti-inflammatory properties and has been used to improve mechanical performance of AF repair constructs [81–86]. Other compounds under preclinical investigation include tanshinone, aucubin, piperine, and juglone [87–90]. - Biotherapy approaches (summary): IL-1 receptor antagonist (IL-1Ra) and TNF-α inhibitors block key proinflammatory cytokine signaling and reduce ECM degradation in vitro and in vivo models [92–99]. Enzyme-based strategies (e.g., lactate oxidase combined with catalase) are designed to reduce lactate-driven acidification and associated inflammation in the avascular disc [100–102].
|
10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
results
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::0:::5
| -7,063,273,121,403,357,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- Biotherapy approaches (summary): IL-1 receptor antagonist (IL-1Ra) and TNF-α inhibitors block key proinflammatory cytokine signaling and reduce ECM degradation in vitro and in vivo models [92–99]. Enzyme-based strategies (e.g., lactate oxidase combined with catalase) are designed to reduce lactate-driven acidification and associated inflammation in the avascular disc [100–102]. mRNA and plasmid delivery approaches enable local production of anti-inflammatory proteins, while miRNA/siRNA strategies silence target inflammatory or catabolic genes (e.g., Caspase-3, ADAMTS5), though these nucleic acids require stabilization and carriers for efficient, sustained delivery [103–114]. MSC transplantation provides paracrine immunomodulation, macrophage M2 polarization, and trophic support; MSC-derived exosomes replicate many paracrine benefits without risks associated with cell engraftment [116–123]. Platelet-rich plasma (PRP) delivers growth factors (TGF-β1, PDGF, etc.) that modulate NF-κB and support ECM synthesis, although PRP standardization and variable efficacy remain challenges [123–126].
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results
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::1:::0
| -8,269,462,034,563,715,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
2) Naturally derived polymer carriers. Natural polymers are favored for biocompatibility and bioactivity but often require reinforcement for load-bearing applications. - Hyaluronic acid (HA): a hydrophilic glycosaminoglycan that binds water and signals via CD44; high-molecular-weight HA reduces TLR/MyD88/NF-κB signaling, decreases IL-1β and nerve growth factor expression, and can function as a drug or cell carrier [127–132]. - Collagen and gelatin: major ECM components providing cell adhesion motifs (RGD); gelatin-based hydrogels and microparticles support cell attachment, proliferation, and drug delivery but need crosslinking or composites to match NP mechanics [133–137]. - Chitosan: a cationic polysaccharide with hemostatic and antimicrobial properties that forms temperature- and pH-responsive hydrogels suitable for controlled release and gene delivery; mechanical reinforcement is typically needed for NP-mimetic applications [138,139]. - Alginate: an anionic polysaccharide crosslinked by divalent cations (e.g., Ca2+) to form hydrogels with tunable stiffness; alginate beads have been used intradiscally and can reduce TNF-α/IL-6 levels, but ionically crosslinked gels are susceptible to ion exchange and mechanical instability [140–142].
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results
| null | 1
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::1:::1
| -3,527,340,590,090,704,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- Chitosan: a cationic polysaccharide with hemostatic and antimicrobial properties that forms temperature- and pH-responsive hydrogels suitable for controlled release and gene delivery; mechanical reinforcement is typically needed for NP-mimetic applications [138,139]. - Alginate: an anionic polysaccharide crosslinked by divalent cations (e.g., Ca2+) to form hydrogels with tunable stiffness; alginate beads have been used intradiscally and can reduce TNF-α/IL-6 levels, but ionically crosslinked gels are susceptible to ion exchange and mechanical instability [140–142]. - Silk fibroin: a proteinaceous biomaterial with high mechanical strength and slow degradation; silk/HA composites and biphasic silk scaffolds have been engineered to better match AF/NP architecture and act as sustained-release carriers [143–146].
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results
| null | 1
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::2:::0
| 8,788,885,909,882,524,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
3) Synthetic polymer carriers. Synthetic polymers impart tunable mechanics, degradation, and manufacturing reproducibility but can produce acidic degradation products or lack intrinsic bioactivity. - PLA/PLGA: widely used for microspheres and nanoparticles enabling sustained drug release; however, acidic degradation products of PLGA can provoke local inflammation and destabilize labile proteins [148–155]. - PCL: semi-crystalline polyester with slow degradation, often electrospun into aligned fibers to mimic AF lamellae [156–162]. - Poly(ester amide) (PEA): incorporates amino-acid–derived units to improve hydrogen bonding and protein-like properties; PEAs have been formed into microspheres and fibers for drug and gene delivery [163–170]. - PVA and other hydrophilic polymers: PVA hydrogels can be engineered with cartilage-like mechanics and modified with adhesion peptides (e.g., RGD) to enhance cell interactions [171–179]. - Thermoresponsive and polyurethane systems (pNIPAAm, PEG copolymers, PU adhesives): allow in situ gelation or AF sealing and tunable mechanical behavior [180–184].
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| null | 2
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::3:::0
| 1,438,536,604,568,350,700
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
4) Nanodelivery systems (summary of representative examples in Table 2). Nanocarriers protect cargo, allow cellular uptake, and can be designed for stimulus responsiveness, targeting, and co-delivery of multiple cargo types. Representative systems include:
- FT-C60 (functionalized fullerene, 2019): fullerene conjugated to an FPR-1–targeting peptide to target activated macrophages after systemic administration, reducing proinflammatory factor expression in macrophages and inflammation at injury sites [199]. - Diclofenac-loaded nanoparticles (Df-NPs, 2016): used in bovine organ culture to downregulate IL-6/IL-8 and MMP1/MMP3 and reduce PGE2 while increasing ECM proteins [223,224]. - PLGA-ABT263 (2021): PLGA nanoparticles delivering the senolytic ABT263 in situ to selectively eliminate senescent cells, reduce SASP cytokines and matrix proteases, and inhibit IVDD progression [201].
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| null | 3
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::3:::1
| -6,459,576,034,797,572,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- Diclofenac-loaded nanoparticles (Df-NPs, 2016): used in bovine organ culture to downregulate IL-6/IL-8 and MMP1/MMP3 and reduce PGE2 while increasing ECM proteins [223,224]. - PLGA-ABT263 (2021): PLGA nanoparticles delivering the senolytic ABT263 in situ to selectively eliminate senescent cells, reduce SASP cytokines and matrix proteases, and inhibit IVDD progression [201]. - LUT-pTGF-β1@PBC (2022): ROS-responsive poly(β-amino ester)-poly(ε-caprolactone) nanoparticles co-delivering luteolin and TGF-β1 pDNA; suppressed COX-2 and IL-6 and restored ECM anabolism/catabolism balance via TGF-β1 [202]. - Fullerol nanoparticles (2013): free radical scavengers that suppressed MMP1/3/13 and TNF-α and prevented adipogenic differentiation of vertebral bone marrow stromal cells [203].
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| null | 3
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::3:::2
| 999,909,212,634,427,900
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- LUT-pTGF-β1@PBC (2022): ROS-responsive poly(β-amino ester)-poly(ε-caprolactone) nanoparticles co-delivering luteolin and TGF-β1 pDNA; suppressed COX-2 and IL-6 and restored ECM anabolism/catabolism balance via TGF-β1 [202]. - Fullerol nanoparticles (2013): free radical scavengers that suppressed MMP1/3/13 and TNF-α and prevented adipogenic differentiation of vertebral bone marrow stromal cells [203]. - Oxymatrine-loaded liposomes (OMT-LIP, 2022): intravenous liposomal oxymatrine targeted inflammatory sites, reduced MMP3/9 and IL-6, mitigated ECM degeneration, and protected NP cells via NF-κB inhibition [209]. - siRNA lipoplexes (2019): cationic liposomes delivering siRNAs against Caspase-3 and ADAMTS5 for intradiscal gene silencing, reducing apoptosis and matrix degradation [113].
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| null | 3
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::3:::3
| -4,952,489,149,314,464,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- Oxymatrine-loaded liposomes (OMT-LIP, 2022): intravenous liposomal oxymatrine targeted inflammatory sites, reduced MMP3/9 and IL-6, mitigated ECM degeneration, and protected NP cells via NF-κB inhibition [209]. - siRNA lipoplexes (2019): cationic liposomes delivering siRNAs against Caspase-3 and ADAMTS5 for intradiscal gene silencing, reducing apoptosis and matrix degradation [113]. - Esterase-responsive PEG-PIB nanomicelles (2023): ibuprofen-containing nanomicelles preloaded into NP progenitor cells (NPPCs) for sustained intradiscal ibuprofen release, inhibiting NPPC pyroptosis and enhancing proliferation/differentiation [211].
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| null | 3
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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| 1,260,241,824,764,043,300
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Mechanistic classes of nano-systems: liposomes protect proteins and nucleic acids but cationic lipids can be cytotoxic; nanomicelles encapsulate hydrophobic drugs and can be designed as enzyme-responsive carriers; nanozymes (e.g., NAC-derived carbon dots, Prussian blue nanoparticles) mimic antioxidant enzymes (SOD, catalase) to scavenge ROS and ameliorate oxidative stress–driven degeneration [215–217]. Inorganic nanoparticles (iron oxide, gold) and dendrimers (PAMAM) offer additional imaging or delivery modalities but require safety evaluation [218–222]. (Figure 3 description). Representative nanosystem schematics include ROS-responsive nanoparticles co-delivering small molecules and pDNA to NPCs, fullerene-based macrophage-targeting conjugates, COX-2–selective fluorescent probes for imaging inflamed discs, and esterase-responsive nanomicelles preloaded into NP progenitor cells for sustained anti-inflammatory release. 5) Microsphere-based delivery systems (summary of Table 3). Microspheres (≈1–250 μm) provide sustained release and can be fabricated from natural or synthetic polymers.
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| null | 4
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::4:::1
| -7,854,537,780,309,458,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
5) Microsphere-based delivery systems (summary of Table 3). Microspheres (≈1–250 μm) provide sustained release and can be fabricated from natural or synthetic polymers. Representative examples include:
- EGCG-loaded gelatin microparticles (2019): epigallocatechin-3-gallate released from gelatin microparticles inhibited IL-1β–induced IL-6/IL-8/COX-2 and MMP expression, protected mitochondrial membranes via PI3K/Akt signaling, and reduced oxidative stress–induced cell death in cell/organ models [236]. - MS@MCI (2022): hydrogel microspheres functionalized with MnO2 and lactate oxidase to eliminate oxidative and inflammatory stress, enhance oxygenation and lactate clearance, and promote ECM metabolism and cell survival after in situ injection [232]. - psh-circSTC2-lipo@MS (2022): lipoplexes targeting circSTC2 grafted onto hyaluronic-acid–derived microspheres for in situ circRNA silencing to preserve ECM metabolism under nutrient-deficient conditions [234]. - NP-IC–seeded GDF-5 gelatin microspheres (2019): microspheres delivering iPSC-derived NP-like cells and GDF-5 restored disc height and water content and improved NP cell/ECM recovery in preclinical models [235].
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| null | 4
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::4:::2
| -2,543,074,065,751,050,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- psh-circSTC2-lipo@MS (2022): lipoplexes targeting circSTC2 grafted onto hyaluronic-acid–derived microspheres for in situ circRNA silencing to preserve ECM metabolism under nutrient-deficient conditions [234]. - NP-IC–seeded GDF-5 gelatin microspheres (2019): microspheres delivering iPSC-derived NP-like cells and GDF-5 restored disc height and water content and improved NP cell/ECM recovery in preclinical models [235]. - CXB-PEAMs (2018): celecoxib-loaded poly(ester amide) microspheres delivered intradiscally and produced anti-inflammatory and analgesic effects via COX-2 inhibition [72]. - Catalase-loaded polymer capsules coated with tannic acid (2018): antioxidant capsules reduced proteolytic enzyme expression in IL-1β–stimulated NP inflammation models [242]. - Mg@PLPE MS (2023): ROS-responsive microspheres with an Mg core and ROS-labile shell that generate H2 and exert antioxidative effects to attenuate ECM breakdown and cell death in rat IVDD models [238].
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| null | 4
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::4:::3
| 5,747,366,218,567,740,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
- Catalase-loaded polymer capsules coated with tannic acid (2018): antioxidant capsules reduced proteolytic enzyme expression in IL-1β–stimulated NP inflammation models [242]. - Mg@PLPE MS (2023): ROS-responsive microspheres with an Mg core and ROS-labile shell that generate H2 and exert antioxidative effects to attenuate ECM breakdown and cell death in rat IVDD models [238]. - PLGA microspheres with IL-1Ra (2012): sustained IL-1Ra release (~20 days) attenuated IL-1β–mediated degradation in engineered NP constructs [240]. - PLLA porous microspheres grafted with bovine serum albumin nanoparticles carrying rhsTNFRII (2012): achieved sustained TNF-α blockade and promoted NP regeneration [241].
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results
| null | 4
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::5:::0
| -7,234,603,084,623,823,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Natural polymer microspheres (gelatin, HA, alginate) are biocompatible and can be functionalized with nanozymes or gene carriers to combine antioxidant, metabolic, and gene-silencing activities [232,234,236]. Synthetic microspheres (PLGA, PEAM, PLLA) enable tunable release kinetics and mechanical stability but must be designed to minimize acidic degradation products and inflammatory responses [72,238,240,241]. ( Figure 4 and Figure 5 descriptions summarize these microsphere constructs and their in vivo/in vitro outcomes.) 6) Hydrogels and composite injectable systems (summary of Table 4). Hydrogels provide injectable, often tissue-mimetic matrices for sustained drug/cell/exosome delivery and can be designed to be stimuli-responsive, self-healing, or mechanically reinforced. - Naturally derived hydrogels: HA, GelMA, chitosan, collagen, genipin-crosslinked fibrin (FibGen), and decellularized ECM (dECM) hydrogels have inherent bioactivity.
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| null | 5
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::5:::1
| -8,112,794,693,400,444,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
Hydrogels provide injectable, often tissue-mimetic matrices for sustained drug/cell/exosome delivery and can be designed to be stimuli-responsive, self-healing, or mechanically reinforced. - Naturally derived hydrogels: HA, GelMA, chitosan, collagen, genipin-crosslinked fibrin (FibGen), and decellularized ECM (dECM) hydrogels have inherent bioactivity. Examples include ASP-Lip@GelMA (aspirin-loaded liposomes in GelMA) to attenuate postoperative inflammation [247], inflammation/ROS-responsive hydrogels co-delivering curcumin and antagomir-21 to promote autophagy and M2 polarization [249], and dECM hydrogels loaded with adipose-derived MSC exosomes (dECM@exo) to inhibit NPC pyroptosis and regulate metalloproteinases [250,251]. FibGen has been used as an AF sealant and a sustained-release vehicle for infliximab to reduce proinflammatory cytokines [98]. - Synthetic hydrogels: thermoresponsive pNIPAAm-MgFe layered double hydroxide hydrogels and PCLA-PEG-PCLA gels have been used for intradiscal celecoxib delivery with sustained analgesia and anti-inflammatory effects [71,73,254].
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| null | 5
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::5:::2
| -1,706,827,849,851,985,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
FibGen has been used as an AF sealant and a sustained-release vehicle for infliximab to reduce proinflammatory cytokines [98]. - Synthetic hydrogels: thermoresponsive pNIPAAm-MgFe layered double hydroxide hydrogels and PCLA-PEG-PCLA gels have been used for intradiscal celecoxib delivery with sustained analgesia and anti-inflammatory effects [71,73,254]. ROS-scavenging hydrogels (e.g., rapamycin-loaded ROS-labile scaffolds) reduce M1 macrophages, upregulate Nrf2/Keap1 antioxidant signaling, and protect CEPs and NP cells from oxidative damage and senescence [255,256]. Composite scaffolds combining PLGA microspheres with IL-4 and kartogenin in OPF/SMA hydrogels can orchestrate macrophage M2 polarization and ECM synthesis [257].
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| null | 5
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::results::::::5:::3
| 5,720,472,393,839,846,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
ROS-scavenging hydrogels (e.g., rapamycin-loaded ROS-labile scaffolds) reduce M1 macrophages, upregulate Nrf2/Keap1 antioxidant signaling, and protect CEPs and NP cells from oxidative damage and senescence [255,256]. Composite scaffolds combining PLGA microspheres with IL-4 and kartogenin in OPF/SMA hydrogels can orchestrate macrophage M2 polarization and ECM synthesis [257]. - Composite and stimulus-responsive hydrogels: ferulic-acid–functionalized gelatin/chitosan thermosensitive hydrogels (FA-G/C/GP) provide sustained antioxidant/anti-inflammatory delivery [258]; self-healing Schiff-base hydrogels delivering siSTING enable sustained STING/NF-κB pathway silencing [259]; hydrogels incorporating ceria-modified mesoporous silica nanoparticles plus TGF-β3 remove ROS and recruit AF cells for ECM deposition [261]. Numerous other composite strategies combine anti-inflammatory drugs, growth factors, gene silencing agents, and nanoparticles to achieve sequential or on-demand release [257,263–265]. ( Figures 6–8 descriptions illustrate representative hydrogel systems and their anti-inflammatory/regenerative activities.)
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| null | 5
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
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10.1016/j.bioactmat.2023.11.021:::results::::::6:::0
| 6,660,650,525,185,885,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — RESULTS
7) Electrospun nanofibers for AF repair. Aligned electrospun fibers (commonly PCL) replicate AF lamellae and can be loaded with anti-inflammatory agents (ibuprofen, berberine, fucoidan) and growth factors (TGF-β3) in core–shell designs that provide rapid outer-layer drug release with sustained inner-layer growth factor release. Limitations include pore-size–dependent cell infiltration, geometry/implantation constraints, and fabrication scalability issues [270–275]. Efficacy summary. Collectively, preclinical studies demonstrate that biomaterial-enabled delivery can reduce proinflammatory cytokine expression (TNF-α, IL-1β, IL-6), decrease matrix-degrading enzyme activity (MMPs, ADAMTS), scavenge ROS, shift macrophage phenotypes toward M2, deliver nucleic acids to silence catabolic or inflammatory genes, remove lactate-driven acidification, and, in some models, restore disc height, hydration, and ECM composition. Most successes are currently limited to in vitro cultures, organ explants, and small-animal models; large-animal translational data and standardized safety assessments are less extensive.
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| null | 6
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::discussion::::::0:::0
| 1,999,261,815,752,148,500
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — DISCUSSION
Advantages of biomaterial-enabled anti-inflammatory strategies. Biomaterials address critical limitations of systemic or direct intradiscal administration by (1) prolonging local residence time, (2) protecting labile cargo (proteins, nucleic acids, exosomes) from degradation, (3) enabling targeted or stimuli-responsive release (pH-, ROS-, enzyme-, esterase-responsive designs), (4) combining multiple functionalities (anti-inflammatory, antioxidant, pro-chondrogenic), and (5) providing mechanical support or AF sealing in conjunction with biological modulation. Composite systems that spatially and temporally control delivery (e.g., outer-layer rapid anti-inflammatory release with inner-layer sustained regenerative signaling) are particularly attractive. Translational and technical challenges. Despite promising preclinical results, several challenges must be addressed for clinical translation:
- Complex inflammatory biology: IVDD inflammation involves networks of cytokines, chemokines, and cellular interactions; single-cytokine targeting (e.g., IL-1β alone) may be insufficient. Systems-level analysis and combination approaches may be required. - Preclinical models: Needle-puncture models are convenient but imperfectly mimic human IVDD etiology and chronicity. Mechanically induced, age-related, and genetically predisposed models (and large-animal models that replicate human spine biomechanics) are necessary to better assess translational potential.
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discussion
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::discussion::::::0:::1
| 7,946,331,321,016,689,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — DISCUSSION
- Preclinical models: Needle-puncture models are convenient but imperfectly mimic human IVDD etiology and chronicity. Mechanically induced, age-related, and genetically predisposed models (and large-animal models that replicate human spine biomechanics) are necessary to better assess translational potential. - Biocompatibility and breakdown products: Degradation products (e.g., acidic PLGA breakdown) can exacerbate inflammation; long-term biocompatibility near spinal nerves and vasculature must be rigorously evaluated. Nano-safety (biodistribution, off-target effects, organ accumulation) is a critical concern for systemic or locally diffusive nanosystems. - Manufacturing and standardization: Complex composite systems (multimaterial, multifunctional) pose challenges for scalable, reproducible Good Manufacturing Practice (GMP) production, sterility, and regulatory approval. - Delivery and containment: Ensuring intradiscal placement without leakage, providing AF repair/sealants where needle puncture risks re-leakage, and controlling burst release remain practical issues. - Hostile microenvironment: The degenerated disc is acidic, hypoxic, and oxidatively stressed; carriers must protect cargo and sometimes actively modulate the environment (e.g., nanozymes that scavenge ROS or enzymes that consume lactate) to improve cell survival and function.
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discussion
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::discussion::::::0:::2
| 7,351,882,595,447,224,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — DISCUSSION
- Delivery and containment: Ensuring intradiscal placement without leakage, providing AF repair/sealants where needle puncture risks re-leakage, and controlling burst release remain practical issues. - Hostile microenvironment: The degenerated disc is acidic, hypoxic, and oxidatively stressed; carriers must protect cargo and sometimes actively modulate the environment (e.g., nanozymes that scavenge ROS or enzymes that consume lactate) to improve cell survival and function. - Cell therapy limitations: Live-cell transplantation (MSCs or NP-like cells) is limited by poor survival in degenerated discs, potential immune reactions, and tumorigenicity concerns; cell-free approaches (exosomes, secretomes) may circumvent some risks while retaining therapeutic benefit.
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discussion
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::discussion::::::1:::0
| -831,511,872,836,209,900
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — DISCUSSION
Key priorities and research directions. The literature suggests several priorities to accelerate translation:
1. Develop multifunctional platforms that combine anti-inflammatory, antioxidant, immunomodulatory, and pro-regenerative cues with spatiotemporal control. 2. Design stimuli-responsive systems that release therapeutics in response to IVDD-specific cues (ROS, pH, enzyme activity) to match local pathology. 3. Use advanced preclinical models (large animals, mechanically relevant loading, aged animals) and standardized outcome measures to improve translational predictability. 4. Emphasize safety testing near neural and vascular structures, long-term biodegradation profiling, and nano-bio interactions. 5. Integrate immune-modulatory strategies (e.g., macrophage recruitment/education, SASP suppression, senolytics) with tissue engineering. 6. Solve manufacturing and sterilization challenges for complex composites to meet regulatory standards. 7. Consider combined strategies that (a) blunt acute inflammation and oxidative stress, (b) restore a permissive microenvironment for cell survival, and (c) supply cells or instruct endogenous repair processes to rebuild ECM and restore biomechanics.
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discussion
| null | 1
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::discussion::::::2:::0
| -6,088,384,591,077,365,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — DISCUSSION
Overall, while biomaterial-based anti-inflammatory approaches show strong mechanistic rationale and encouraging preclinical efficacy, careful optimization of materials, cargos, delivery methods, and translational models is needed to realize durable, safe clinical therapies.
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discussion
| null | 2
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1
|
10.1016/j.bioactmat.2023.11.021:::conclusion::::::0:::0
| -3,235,007,207,592,660,500
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — CONCLUSION
Modulating the inflammatory microenvironment with biomaterial-enabled delivery systems is a promising strategy to delay IVDD progression and support tissue regeneration. Injectable, stimuli-responsive, and composite biomaterials enable localized, sustained delivery of anti-inflammatory drugs, biologics, nucleic acids, and cell-derived products while providing mechanical support or AF sealing. Multifunctional platforms that combine antioxidative activity, immune modulation (macrophage M1→M2 polarization, SASP suppression), gene silencing or gene expression, and regenerative signaling (growth factors, cell recruitment) are most likely to achieve meaningful disc repair. Translation will require rigorous safety testing, standardized manufacturing, and clinically relevant preclinical models. Continued interdisciplinary work across biomaterials science, immunology, biomechanics, and translational medicine is essential to develop durable and safe regenerative therapies for IVDD.
|
10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
conclusion
| null | 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 1.3
|
10.1016/j.bioactmat.2023.11.021:::methods:::methods:::0:::0
| 4,281,304,200,657,459,000
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration — METHODS / methods
This manuscript is a narrative review synthesizing published preclinical and translational literature on inflammatory mechanisms in IVDD and biomaterial-based therapeutic strategies. The original source did not provide a detailed systematic search strategy or prespecified inclusion/exclusion criteria. The review integrates mechanistic studies, in vitro organ/cell culture experiments, in vivo animal models, and representative biomaterial design strategies described in the primary literature.
|
10.1016/j.bioactmat.2023.11.021
|
Progress in regulating inflammatory biomaterials for intervertebral disc regeneration
|
methods
|
methods
| 0
|
["Intervertebral disc", "Anti-Inflammation", "Biomaterials", "Tissue regeneration"]
| 0.9
|
10.1016/j.isci.2020.101519:::title::::::0:::0
| 1,210,653,036,923,139,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — TITLE
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
title
| null | 0
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::abstract::::::0:::0
| 1,099,735,987,893,595,900
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — ABSTRACT
Advances in reading, writing, and editing DNA are providing unprecedented insights into the complexity of immunological systems. This combination of systems and synthetic biology methods is enabling quantitative and precise understanding of molecular recognition in adaptive immunity, thus providing a framework for reprogramming immune responses for translational medicine. In this review we highlight state-of-the-art methods such as immune repertoire sequencing, immunoinformatics, and immunogenomic engineering and their application toward adaptive immunity. We showcase novel and interdisciplinary approaches that have the promise of transforming the design and breadth of molecular and cellular immunotherapies.
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
abstract
| null | 0
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1.3
|
10.1016/j.isci.2020.101519:::introduction::::::0:::0
| 6,542,554,000,661,615,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — INTRODUCTION
Adaptive immunity is mediated primarily by B and T lymphocytes, which mount molecularly targeted responses against pathogens and provide both short-term and long-term protection. Antigen recognition and specificity are encoded in adaptive immune receptors: B cell receptors (BCRs; antibodies in secreted form) and T cell receptors (TCRs). BCRs are composed of heavy (HC) and light (LC) chains; TCRs typically comprise alpha (α) and beta (β) chains (alternatively gamma (γ) and delta (δ) chains in some T cells). The enormous diversity of BCRs and TCRs required to recognize a wide array of antigens is generated during lymphocyte development by somatic recombination of germline variable (V), diversity (D), and joining (J) gene segments (V(D)J recombination) (Tonegawa, 1983). Imprecise joining and template-independent nucleotide addition or deletion during recombination, combined with combinatorial pairing of receptor chains and (for B cells) somatic hypermutation, yield highly individualized repertoires. Extrinsic factors (pathogens, vaccination) and intrinsic factors (tumors, autoimmunity, aging) continuously shape repertoire composition and dynamics, producing a unique immunological fingerprint for each individual (Greiff et al., 2015a).
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
introduction
| null | 0
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::introduction::::::1:::0
| 8,162,050,174,578,470,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — INTRODUCTION
Rapid technological progress in sequencing, single-cell profiling, computational analysis, and genome engineering is transforming how adaptive immunity is read, written, and edited. High-throughput immune-repertoire sequencing and single-cell methods provide granular views of receptor sequence diversity and cellular phenotypes (Emerson et al., 2017; Galson et al., 2015; Egorov et al., 2018; Bashford-Rogers et al., 2019, 2016; Papalexi and Satija, 2018). Immunoinformatics—computational and statistical frameworks tailored to immune data—aims to decode sequence patterns that reflect antigen specificity and clonal selection (Kidd et al., 2014; Shugay et al., 2018; Brown et al., 2019). Complementing these readouts, synthetic display technologies (phage, yeast, mammalian display) and immunogenomic engineering (including CRISPR-based editing) enable empirical interrogation and redesign of receptor specificity and function (Pogson et al., 2016; Eyquem et al., 2017). The integration of sequencing, computational inference, and experimental engineering offers a framework to discover immune specificities, generate therapeutic receptors, and reprogram cells to act as "living drugs" that sense and respond to disease (June et al., 2018; Li et al., 2019).
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
introduction
| null | 1
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::introduction::::::1:::1
| -4,929,769,308,357,648,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — INTRODUCTION
2018; Li et al., 2019). The review that follows summarizes the current state of these complementary approaches—reading, writing, and editing adaptive immunity—highlights representative methods and platforms, and outlines translational opportunities and outstanding challenges.
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
introduction
| null | 1
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::0:::0
| -4,691,504,896,336,666,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
This review frames adaptive-immunity research around three complementary capabilities: reading (sequencing and single-cell profiling), writing (synthetic library generation and display), and editing (genome-engineering of immune cells). Each capability has matured substantially and, when integrated, enables discovery and translational engineering of immune receptors and cells. Reading: strengths, limitations, and opportunities
High-throughput short-read sequencing (Illumina) enables deep sampling of repertoires and remains the workhorse for repertoire profiling because of its throughput and low per-base error rate (Metzker, 2010; Pfeiffer et al., 2018). However, short reads can disconnect naturally paired receptor chains (VH–VL or Vα–Vβ) when chain transcripts are on separate molecules; single-cell approaches (10x Genomics and related platforms) address this by barcoding person-specific transcripts, enabling digital pairing and joint transcriptome–receptor profiling (Zheng et al., 2017). Long-read technologies (PacBio, Oxford Nanopore) enable contiguous sequencing of linked chains and full-length recombinant antibody fragments, which is valuable for drug-discovery workflows and for verifying chain pairing from screening libraries (DeKosky et al., 2013; McDaniel et al., 2016; Wenger et al., 2019; Payne et al., 2019).
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 0
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::1:::0
| -6,333,004,601,675,463,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
A central computational challenge for reading is accurate error correction and germline assignment. Sequencing and PCR errors artificially inflate apparent clonal diversity and can confound downstream analyses; UMIs and consensus-based error correction are effective mitigations (Shugay et al., 2014; Turchaninova et al., 2016). Germline-allele incompleteness biases V(D)J assignment, and analytic pipelines should incorporate tools for germline discovery and personalized germline inference (TIgGER, IgDiscover) to minimize assignment errors (Gadala-Maria et al., 2015, 2019; Corcoran et al., 2016). Clonotyping strategies must balance sensitivity (aggregation of true clonal relatives) against specificity (avoiding merging independent clones), and adaptive or probabilistic approaches outperform fixed-distance cutoffs when somatic hypermutation is variable (Ralph and Matsen, 2016; Nouri and Kleinstein, 2018, 2020). Beyond catalogs of sequences, recent work aims to infer antigen specificity from repertoire features. Methods such as TCRdist and GLIPH identify conserved motifs and similarity groups correlated with antigen recognition (Dash et al., 2017; Glanville et al., 2017). Machine-learning approaches—supervised and unsupervised—exploit labeled antigen-specific data to build classifiers and generative models for specificity prediction and for designing variants with improved properties (Friedensohn et al.,
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 1
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::1:::1
| 6,288,949,890,534,959,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
2017). Machine-learning approaches—supervised and unsupervised—exploit labeled antigen-specific data to build classifiers and generative models for specificity prediction and for designing variants with improved properties (Friedensohn et al., 2020; Mason et al., 2019). Limitations include the scarcity of high-quality labeled datasets for many antigens, potential overfitting to experimental biases, and the need to carefully assess generalization to broader repertoires.
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 1
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::2:::0
| -6,724,216,095,388,396,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
Writing: display technologies and library screening
Phage and yeast display remain central tools for in vitro selection of antigen-binding receptors. Phage can present very large libraries (up to ~10^11 variants), enabling broad exploration of sequence space, while yeast display provides eukaryotic folding and quantitative FACS-based selection (Smith, 1985; Boder and Wittrup, 1997; Benatuil et al., 2010). Integration of deep sequencing into panning workflows has revealed that panning dynamics can deplete desirable clones (fitness vs binding tradeoffs) and that tracking sequence abundance across rounds enables informed clone recovery (Ravn et al., 2010; Saggy et al., 2012; Wang et al., 2010). However, binders identified in fragment formats (scFv, Fab) do not always translate to full IgG formats or to functional TCR signaling, motivating mammalian-display approaches.
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 2
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::3:::0
| 9,138,759,064,226,384,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
Mammalian-display approaches and endogenous-locus targeting (CRISPR-based HDR) enable screening in a more physiological expression context and permit simultaneous display and secretion of full-length IgG (Pogson et al., 2016; Parola et al., 2019). These methods reduce artifacts from prokaryotic expression and support downstream functional assays in mammalian cells. They are particularly powerful when combined with targeted mutagenesis libraries generated via CRISPR HDR or degenerate oligonucleotide libraries introduced at endogenous loci (Mason et al., 2018). Editing: genome engineering for cellular therapies and synthetic immunity
CRISPR-based editing has accelerated functional engineering of lymphocytes. Targeted knock-in of CARs or TCRs into the endogenous TRAC locus produces uniform expression and, in some reports, improved activity and reduced tonic signaling compared with random viral integration (Eyquem et al., 2017). Multiplex editing strategies (knock-in plus knockouts, e.g., PDCD1) aim to enhance persistence and activity (Roth et al., 2018; Stadtmauer et al., 2020). Nevertheless, there are tradeoffs: complete knockout of the endogenous TCR may reduce long-term persistence in some contexts (Stenger et al., 2020).
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 3
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::3:::1
| 3,713,636,446,289,053,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
Nevertheless, there are tradeoffs: complete knockout of the endogenous TCR may reduce long-term persistence in some contexts (Stenger et al., 2020). Moreover, affinity-enhanced TCRs and CARs have caused severe off-target and on-target, off-tumor toxicities in clinical settings, highlighting the need for rigorous cross-reactivity assessments and functional validation beyond in vitro affinity (Morgan et al., 2010; Cameron et al., 2013).
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 3
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
10.1016/j.isci.2020.101519:::discussion::::::4:::0
| 5,419,240,961,447,633,000
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity — DISCUSSION
B cell genome engineering is an emerging and promising direction for synthetic immunity because engineered B cells could function as in vivo factories producing protective antibodies. Early work demonstrated targeted nucleotide knock-ins and, with further optimization (AAV6 donors, extended culture), insertion of predefined BCRs into the endogenous immunoglobulin locus (Wu et al., 2018; Johnson et al., 2018; Hung et al., 2018; Hartweger et al., 2019). Some engineered B cells transferred to immunocompetent mice were shown to clonally expand and accumulate somatic hypermutation following immunization, providing proof-of-concept for adoptive B cell immunization (Nahmad et al., 2020; Huang et al., 2020). Remaining challenges include scaling editing efficiencies, preserving appropriate B cell phenotypes during ex vivo manipulation, ensuring recruitment to germinal-center reactions in vivo, and controlling integration and safety.
|
10.1016/j.isci.2020.101519
|
Immune Literacy: Reading, Writing, and Editing Adaptive Immunity
|
discussion
| null | 4
|
["immune repertoire sequencing", "immunoinformatics", "immunogenomic engineering", "B cell receptor (BCR)", "T cell receptor (TCR)", "single-cell sequencing", "CRISPR", "display technologies", "synthetic immunity", "machine learning"]
| 1
|
A FAISS index + metadata for scientific retrieval
index.faiss: FAISS index (cosine w/ inner product).meta.jsonl: one JSON per chunk; fields include chunk_id, paper_id, title, section, subsection, paragraph_index, keywords, boost.index.info.json: (optional) dimensions, index type, faiss version.bio-protocol/neophyte-retriever (mean-pooled, L2-normalized)IndexFlatIP (or your choice)import faiss, json, numpy as np, hashlib
from huggingface_hub import hf_hub_download
REPO = "bio-protocol/neophyte-faiss-index-v1"
IDX = hf_hub_download(REPO, "index.faiss", repo_type="dataset")
META = hf_hub_download(REPO, "meta.jsonl", repo_type="dataset")
index = faiss.read_index(IDX)
# stable 64-bit ids (must match your build)
def stable64(s: str) -> int:
try:
import faiss
if hasattr(faiss, "hash64"): return int(faiss.hash64(s))
except Exception:
pass
return int.from_bytes(hashlib.blake2b(s.encode(), digest_size=8).digest(), "little", signed=False) - (1<<63)
id2meta = {}
with open(META, "r", encoding="utf-8") as f:
for line in f:
md = json.loads(line)
id2meta[stable64(md["chunk_id"])]=md