Table 1.

Mechanisms of different biomaterials regulating cutaneous wound healing in different stages (Abbreviations: 3D, three‐dimensional; A‐MSC, adipose‐derived mesenchymal stem cell; Ag NP, silver nanoparticle; APC, antigen‐presenting cell; Au NP, gold nanoparticle; bFGF, basic fibroblast growth factor; BG, bioglass; BM‐MSC, bone marrow‐derived mesenchymal stem cell; CM, conditioned medium; Col, collagen; CPO, calcium peroxide; CSF1R, colony‐stimulating factor‐1 receptor; D‐MSC, dermal‐derived mesenchymal stem cell; DNA, deoxyribonucleic acid; EMT, epithelial‐mesenchymal transition; EndMT, endothelial‐mesenchymal transition; GAG, glycosaminoglycan; GF, growth factor; IL, interleukin; MA, methacryloyloxy; MB, microbubble; MRGPRX2, Mas‐related G‐protein coupled receptor member X2; MMP, matrix metalloproteinase; MNGC, multinucleated giant cell; NB, norbornenes; NOCS, N,O‐carboxymethyl chitosan; PAR‐1, protease‐activated receptors‐1; PCL, poly(ε‐caprolactone); PCN, polyethylenimine functionalized ceria nanocluster; PDGF, platelet‐derived growth factor; PDMS, polydimethylsiloxane; PEG, poly(ethylene glycol); PFD, pirfenidone; PLGA, poly(lactic‐co‐glycolic acid); PNIPAM, poly (N‐isopropyl acrylamide); PUAO, polyurethane; PVA, poly(vinyl alcohol); PVC, poly(vinyl chloride); ROS, reactive oxygen species; SA, sodium alginate; sHA3, high‐sulfated hyaluronic acid; TGF, transforming growth factor; TiO₂ NP, titanium oxide nanoparticle; TLR, toll‐like receptor; TNF, tumor necrosis factor; TRAP‐6, thrombin receptor agonist peptide‐6; VEGF, vascular endothelial growth factor; ZnO NP, zinc oxide nanoparticle)

Stage	Bioactive materials	Type of cell or protein	Mechanism	Wound model	Refs.
Hemostasis	Photopolymerized PVA−NB hydrogel particle with TRAP6	Platelets	TRAP6 could activate platelets and aggregation via PAR‐1	Coagulation model	[ 30c ]
	Interpenetrating polymer network dry cryogel	Blood cells/platelets	Catechol group and dopamine could reinforce blood cell/platelet adhesion and activation	Liver trauma, liver incision, and liver cross incision models	[ 35 ]
	Quaternized carboxymethyl chitosan and organic rectorite nanocomposite	Blood cells	The positive charge on the chitosan surface could aggregate blood cells	Skin trauma model	[ 38 ]
Anti‐inflammation	Modular hydrogel consisted of GAG heparin derivatives and star‐shaped PEG	Neutrophils	The hydrogel could eliminate inflammatory chemokines	Chronic venous leg ulcer model	[ 47 ]
	Multilayer coating of heparin−chitosan	Neutrophils	It could downregulate the expression of β2 integrin and reduce neutrophil recruiting	–	[ 49 ]
	β‐sheet Q11 peptide grafted with glucomannan	Macrophages	Activate the mannose receptor to promote its polarization toward the M2 phenotype	Skin trauma model	[ 55 ]
	Negatively charged carboxylic acid‐terminated nanorod	Macrophages	Negative electricity could transform macrophages into an anti‐inflammatory M2 phenotype	–	[ 56 ]
	Stiff natural biopolymer matrices composed of Col I and GAGs	Macrophages	Macrophages demonstrated M2 phenotype on it	–	[ 58 ]
	sHA3 covalent binding to Col fibril	Macrophages	It reduced macrophage M1 response and did not induce MNGC formation	Skin trauma model	[ 59 ]
	3D Col I fibronectin network	Macrophages	It could induce macrophage tolerance	–	[ 60 ]
	Cationic gelatin, cationic dextran, polyethyleneimine, and polylysine	T cells	Cationic polymers could induce potent Th1 responses via IL‐12 secretion mediated by TLR‐4	–	[ 64 ]
	PLGA nanoparticle	T cells	The PLGA nanoparticle act as APCs to promote the proliferation of T cells	Melanoma model	[ 65 ]
	Self‐assembling peptide (RADA)4 bound with PAMP‐12 motif	Mast cells	PAMP‐12 could activate mast cells via the MRGPRX2 receptor	–	[ 67 ]
	PVC surface modified with CD47	Neutrophils	CD47 could reduce neutrophil recruitment and adhesion	–	[ 74 ]
Tissue regeneration and Col deposition	OxOBand encapsulated with A‐MSC‐derived exosomes	Keratinocytes	Exosomes accelerate the migration rate of keratinocytes	Diabetic ulcer model	[ 86 ]
	Engineered human A‐MSC‐derived exosomes	Fibroblasts	miR‐21‐5p could promote reepithelialization through the Wnt/β‐catenin pathway	Diabetic ulcer model	[ 90 ]
	Electrospinning nanofiber scaffold containing Nagelschmidtite	Epithelial cells	Nagelschmidtite could activate both the EMT and EndMT pathways	Diabetic ulcer model	[ 92 ]
	PCL/Col nanofibrous matrix coated with Col gel	Keratinocytes	It could affect the migration of keratinocytes, enhance the expression of MMP‐2 and ‐9, promote the deposition of laminin‐332, and activate integrin β1	–	[ 93 ]
	Human recombinant Col VII	Keratinocytes	Col VII could mediate adhesion between epidermis and dermis in human skin	Recessive dystrophic epidermolysis bullosa model	[ 94 ]
	Microstructured Col membrane	Keratinocytes	The differentiation of keratinocytes was enhanced under the mimic natural 3D structure	–	[ 95 ]
	Tetrahedral DNA nanostructure	Endothelial cells	The nanomaterial could enhance angiogenesis by upregulating Notch signals	–	[ 102 ]
	Bioactive material loaded with VEGF, PDGF, bFGF, and TGF	Endothelial cells	Different GFs could regulate endothelial cells for angiogenesis	–	[ 104 , 105 , 106 , 107 ]
	Borosilicate cross‐linked with SF via MA group loaded with Cu2+	Endothelial cells	The HIF‐1α pathway was restored by interaction with Cu2+	Diabetic ulcer model	[ 112 ]
	Multireactive injectable catechol–Fe3+ coordinated hydrogel	Endothelial cells	It could eliminate ROS, thus promoting neovascularization	Burn wound model	[ 115 ]
	PUAO−CPO cryogel	Endothelial cells	It displayed an excess ROS and reduction of angiogenesis	Ischemic flap model	[ 116 ]
	ZnO NP, TiO2 NP, Ag NP, Au NP lanthanide metallide NP, graphene oxide, and carbon nanotube	Endothelial cells	NPs could induce the formation of ROS and boost endothelial cell migration and incipient tube formation.	–	[ 117 , 118 , 119 , 120 , 121 , 122 , 123 ]
	Bioglass and mesoporous silica nanosphere fabricated on nanofibrous membrane	Endothelial cells	It could release silicon ions and upregulate the expression of genes associated with angiogenesis and new tissue formation	–	[ 100 ]
	Hydrogel based on fayalite and NOCS	Endothelial cells	It could stimulate the GF secretion to promote angiogenesis	Diabetic ulcer model	[ 124 ]
	PCN‐miR/COL hydrogel	Endothelial cells	It could reduce ROS and generate functional neovascularization	Diabetic ulcer model	[ 125 ]
	PNIPAM fiber in PDMS mold	Endothelial cells	3D network could form vascular perfusion throughout the hydrogel implant	Ischemic hindlimb and skin trauma models	[ 126 ]
	Copper‐containing mesoporous glass NP	Endothelial cells	It could promote endothelial cell proliferation and angiogenesis	Infected skin model	[ 128 ]
	MB with hydrogel	Endothelial cells	It could promote O2 diffusion and accelerate wound healing	–	[ 129 ]
	Dual drug‐loaded bilayer nanofibrous sponge‐like 3D scaffold	Fibroblasts	It could promote fibroblast migration and potentiate Col synthesis	Silicone splint model	[ 130 ]
	Nonmulberry silk fibroin	Keratinocytes and fibroblasts	RGD peptide on it could increase recruitment and adhesion of keratinocytes and fibroblasts, which accelerate the granulation formation	Skin trauma model	[ 131 ]
Matrix remodeling	starPEG–heparin hydrogel introducing RGD peptide	Fibroblasts	It could achieve sustained release of TGF‐β to induce fibroblasts into myofibroblasts	–	[ 133 ]
	SF hydrogel	Fibroblasts	It could induce the expression of TNF‐α and CD163	Burn wound model	[ 134 ]
	Sulfated GAGs	MMP	It could inhibit the MMP‐1 and ‐2	–	[ 140 ]
	Silk‐fibroin/gelatin electrospun nanofibrous dressing with astragaloside IV	Myofibroblasts and inflammatory cells	It could reduce TGF‐β1 secretion and Col I/III ratios	Burn wound model	[ 141 ]
	PLA electrospun with IL‐10‐HA‐sol inside and IL‐10 outside	Fibroblasts and macrophages	Released IL‐10 and promoted macrophage polarization toward the M2c phenotype	Skin trauma model	[ 144 ]
	SA/BG‐SACM‐PLGAPFD	Fibroblasts and immune cells	The system could regulate the inflammatory response, promote the formation of vascularized granulation tissue, and prevent fibrosis and scarring of regenerative skin	Diabetic ulcer model	[ 147 ]
	Bioactive material implantation and inhibiting CSF1R	Macrophages	Inhibition of CSF1R could inhibit fibrosis and improve biocompatibility	–	[ 150 ]
	Integra loaded with A‐MSCs and D‐MSCs	Macrophages	Hydrogel combined with stem cells could modulate macrophage polarization.	Skin trauma model	[ 152 ]