Intelligent hydrogel-based dressings for treatment of chronic diabetic wounds

Table 1 Summary of applications of intelligent hydrogel dressings in diabetic wound healing

Components	Structural features	Intelligent responsiveness mechanisms	Application advantages	Ref.
Using GelMA and chitosan methacrylate (CMCSMA) as the GACo MPNs and phenol red	Double cross-linked network structure, cross-linked by photoinitiation, with good injectability, shape adaptability, and mechanical strength	pH response, visual pH monitoring	Antibacterial, anti-inflammatory, angiogenic, real-time pH monitoring	[64]
Based on LAMC, loaded with CDs, ceria oxide-molybdenum disulfide nanoparticles (C@M) and PDA coating (C@M@P)	LAMC is formed by amidation reaction, and nanoparticles are loaded by physical blending, with an interconnected porous structure	pH response, temperature response (photothermal property)	Antibacterial, antioxidant, anti-inflammatory, real-time pH and temperature monitoring	[65]
Composed of different modules, including glucose-responsive hydrogel, pH-responsive hydrogel, and temperature-responsive hydrogel	The glucose-responsive hydrogel is formed by radical polymerization and hydrogen bonding, and combined with the PC structure	Glucose response, pH response, temperature response	Real-time multi-biomarker monitoring (glucose, pH, temperature)	[17]
OHA, borax, gelatin, GOx, Cu2-xSe-BSA nanozyme	Form a network structure through Schiff base bond and borate ester bond dual dynamic crosslinking	Glucose-responsive, triggered by acidic environment	Generate antibacterial substances, regulate immune microenvironment, and promote angiogenesis	[66]
ε-PL, SilMA, TA, Cu²+, Zn²+	Form a concentric circular structure with dual-drug delivery system and different release kinetics through MPN	Cu@TA is released first, followed by Zn@TA	Exert antibacterial, antioxidant, immunomodulatory, and angiogenic effects in sequence	[67]
N-Carboxyethyl chitosan-grafted-phenylboronic acid, oxidized dextran, ε-polylysine-coated manganese dioxide, β-cyclodextrin-reduced graphene oxide/N,N-di-sec-butyl-N,N-dinitroso-1,4-phenylenediamine	Construct a network through Schiff base reaction and phenylboronate ester bond, with porous structure	Responsive to NIR and glucose stimulation, release NO and O2	Conductive, self-healing, antibacterial, antioxidant, and promote wound healing	[68]
Hyaluronic acid, pectin, MnCoO@ε-PL, PTA	Dynamic acylhydrazone and imine bonds, physical cross-linking	pH and ROS dual-responsive	Antibacterial, antioxidant, promote cell survival and proliferation, accelerate wound healing	[69]
Polyacrylamide, polydopamine-doped polypyrrole	Incorporation of conductive polymer nanofibrils	Electro-responsive	Real-time monitoring, on-demand drug delivery, antibacterial, moist and visible environment, promote wound healing	[70]
Heparin, ultrasmall nanozymes	Incorporation of metal nanoparticles	Enzyme-responsive release of metal ions	Inhibit macrophage-driven inflammation, scavenge ROS, accelerate wound healing	[71]
OPLL, CMCS, GOx, exosomes	Crosslinked by Schiff base covalent bond	pH-responsive drug release	Regulate microenvironment, promote angiogenesis	[72]
CMCS, oligoprocyanidins, oxide dextran, deferoxamine	Crosslinked by imine and hydrogen bonding	pH-triggered drug release	Antioxidant, anti-inflammatory, promote angiogenesis	[73]
GelMA, cerium dioxide loaded with taurine (@Tau)	Microneedle structure	N/A	Antioxidant, anti-inflammatory, anti-aging	[74]
Gelatin hydrogel micropattern and gelatin electrospun membrane	Gelatin hydrogel micropattern is photocrosslinked and further crosslinked with genipin, embedded in gelatin electrospun membrane	N/A	Good integration with regenerated tissue, protect ADSCs, promote DW healing	[75]
HA-PBA-ALD, PVA, ADH, PBNPs, VEGF	Formed by crosslinking HA-PBA-ALD with PVA/ADH through boronate ester bonds and acylhydrazone bonds, PBNPs and VEGF are physically loaded	Responsive to inflammation (pH and ROS-sensitive dynamic covalent bonds)	Controlled release, anti-inflammatory, antioxidant, promote angiogenesis, accelerate wound healing	[76]
PLL-grafted Glu, HA, AAm, TPA, UB	The inner layer is formed by crosslinking PLL-Glu with TPA, the middle layer is a double-network structure of PLL, HA, and UB, the outer layer is crosslinked PLL and AAm	ROS-responsive (degradation of the ROS-responsive layer in the presence of ROS)	Good biocompatibility, adhesion, mechanical strength, antioxidative action, promote angiogenesis, reduce senescence and ROS production, accelerate wound closure	[77]
HA, PBA, tea polyphenol-stabilized silver nanoparticles (TP@Ag nps)	Crosslinked via borate ester bonds between PBA and HA, with TP@Ag NPs incorporated	Glucose-responsive degradation and release of TP@Ag NPs	Antioxidant, antibacterial, anti-inflammatory, accelerated wound healing	[78]
Chitosan, glycidyl trimethylammonium chloride, dextran, sodium Periodate, 1,8-dihydroxynaphthalene, aniline, ammonium persulfate, curcumin	Schiff base reaction between oxidized dextran and quaternized chitosan grafted polyaniline	NIR responsive release of curcumin	Antioxidant, antibacterial, promote nerve regeneration and modulate neuro-immune microenvironment	[79]
CMC, precoordinated europium-ethylenediaminetetraacetic acid complexes	Crosslinked by metal-carboxyl coordination interaction	pH-responsive fluorescence for wound state monitoring	Promote angiogenesis, excellent biocompatibility, self-healing	[80]
Xanthan gum, sodium alginate, HBD peptide nanoparticles, silver ions	Crosslinked with calcium ions and silver ions, forming a 3D dual-network skeleton structure	Ultrasound-responsive, releasing drugs and degrading hydrogel under ultrasound stimulation	Antibacterial, antioxidant, promoting angiogenesis, achieving deep wound penetration	[18]
Thiolated hyaluronic acid, methacrylate gelatin, poly(L-lactic acid) nanoparticles loaded with TGF-β receptor antagonists	Interpenetrating hydrogel scaffold, photocrosslinked	Regulating macrophage polarization and inhibiting scar formation in different stages	Modulating immune microenvironment, remodeling skin tissue, preventing scar formation	[81]
Astragalus polysaccharide, carboxymethyl chitosan, sodium alginate, PPy-PDA-MnO2 nanoparticles loaded with resveratrol	Crosslinked by Schiff base reaction and hydrogen bond, with multiple-network structure	Conductive, can monitor muscle function	Enhancing wound healing, antioxidant, tissue adhesive, conducting electromyography monitoring	[82]
CMC, TA, and quercetin-loaded zeolitic imidazolate framework-8 nanoparticles modified with HA	Crosslinked by dynamic ionic bonds and hydrogen bonds	N/A	Antibacterial, anti-oxidative stress, anti-apoptosis, angiogenesis promotion, ER stress relief	[83]
PVA and BPNS	Doped with BPNS and modified with NaCl	NIR light-responsive photothermal conversion	Electrical stimulation, photothermal effect for antibacterial and wound healing acceleration	[84]
O-CMCS, gelatin methacryloyl, and spermidine	Double network with dynamic imine bonds and non-dynamic photo-crosslinked bonds	N/A	Reduce inflammation, promote macrophage polarization, enhance acute and diabetic wound healing	[83]
Chitosan nanoparticles, carboxymethyl chitosan, bioactive glass, titanium dioxide, MSC-derived exosomes	Chitosan nanoparticles encapsulate exosomes, and bioactive glass and titanium dioxide are loaded in carboxymethyl chitosan hydrogel	The dressing continuously releases bioactive substances to enhance angiogenesis and collagen deposition	Antibacterial, anti-inflammatory, angiogenic, promotes collagen deposition	[85]
Catechol-functionalized chitosan, acrylic acid, catechol functional methacryloyl chitosan-silver nanoparticles, vanillin	Synthesized by one-step thermal polymerization, with aldehyde and phenolic hydroxyl groups forming crosslinks	N/A	Antibacterial, antioxidant, anti-inflammatory, regulates macrophage polarization	[86]
Polyacrylamide, sodium alginate, Chlorella	Chlorella is loaded in a semi-interpenetrating network formed by crosslinking acrylamide with alginate chains dispersed	Chlorella photosynthesizes to produce oxygen and bioelectricity in response to light	Produces oxygen and bioelectricity, antibacterial, promotes cell proliferation and migration	[87]
Laponite, poly (acrylic acid), LL37, NanoFlares	Laponite and poly (acrylic acid) form hydrogel matrix, incorporating LL37 and NanoFlares	NanoFlares detect and quantify mRNA biomarkers for real-time wound monitoring	Antimicrobial, monitors wound healing status in real time	[88]

GelMA: Gelatin methacrylate; GACo MPNs: Cobalt-gallic acid metal-phenolic nanoparticles; LAMC: Lipoic acid-modified chitosan; CDs: Carbon quantum dots; PDA: Polydopamine; PC: Photonic crystal; OHA: Oxidized hyaluronic acid; Gox: Glucose oxidase; BSA: Bovine serum albumin; ε-PL: Ε-Poly-L-lysine; SilMA: Silk fibroin; TA: Tannic acid; MPN: Metal-phenolic network; OPLL: Oxidized pullulan polysaccharide; CMCS: Carboxymethyl chitosan; N/A: Not applicable; VEGF: Vascular endothelial growth factor; PVA: Polyvinyl alcohol; HA: Hyaluronic acid; PBA: Phenylboronic acid; PLL: Ε-Poly-L-lysine; Glu: Glucose; Aam: Acrylamide; TPA: N-(4boronobenzyl)-N′-(4 boronophenyl)-N,N,N′,N′-tetramethylpropane-1,3-diaminium; UB: Urolithin B; NIR: Near-infrared; CMC: Carboxymethyl cellulose; TGF-β: Transforming growth factor-β; BPNS: Black phosphorus nanosheets.