Table 4.

Studies (2012–17) on repairing skin tissue using composite biomaterials

Classification	Material	Fabrication method	Biological in vitro results	Biological in vivo results	Reference
Natural polymers–natural polymers	Gelatin–HA	Electrospinning and cross-linking	—	Gelatin–HA on artificial wounds in live rat model for 14 days: more epidermis and fewer inflammatory cells were found in GE/HA nanofiber and ChitoHeal gel groups than in antiseptic gauze group.	[105]
Natural polymers–ECM	Decellularized peritoneum– HA–EGF	1. Coating decellularized peritoneum with sodium hyaluronate 2. Soaking in EGF solution	NIH3T3 cells cultured in culture medium containing EGF for 96 h; MTT assay: cell viability increased as EGF concentrations increased.	Scaffolds on artificial wounds in live rabbit model for 20 days: decellularized peritoneum–HA–EGF group recovered best among all groups, with wound-healing rates of 87.41% after 20 days post-surgery; thicker epidermis and dermis layers were observed in decellularized peritoneum–HA–EGF group than in decellularized peritoneum group.	[106]
Natural polymers–synthetic polymers	PCL–CA–CS–collagen	1. Co-electrospinning of PCL and CA 2. Alternately soaking in CS and collagen solutions every 20 min	Cytotoxicity assay: NHDFs seeded on scaffolds for 72 and 120 h; MTT assay, flow cytometry analysis and ultrastructure: cell viability and cell density in PCL–CA–CS–collagen group were higher than those in other groups; mitochondria in cells with cytoplasmic vacuolization appeared to be normal with increase in number of CS/collagen bilayer coatings on PCL–CS mats. Cell migration assay: NHDFs seeded on scaffolds for 7 days; optical microscopy: NHDF migration into wound area of PCL–CA–CS–collagen was greatly enhanced with increase in number of bilayer coatings.	Fibroblast-seeded scaffolds on artificial wounds in live rat model for 7 days: the CS/collagen coatings in scaffolds had positive effect on neovascularization and led to increased wound-healing rate; fibroblast-seeded PCL–CA–CS–collagen promoted complete re-epithelialization and regeneration of skin appendages; regenerated skin with fibroblast-seeded PCL–CA–CS–collagen covering exhibited smooth surface and loose collagen fibre arrangement similar to that of normal skin.	[107]
	Castor-oil-based polymer–CS–ZnO	1. Mixing castor oil with CS–ZnO nanoparticles 2. Reacting with HDI 3. Crosslinking using GLA	Cell viability study: NHDF incubated in bionanocomposites for 72 h; alamarBlue assay: castor-oil-based polymer–CS–ZnO whose CS–ZnO loading rate ≤ 5.0 wt% showed no toxic effects. Antimicrobial assay: castor-oil-based polymer–CS–ZnO exhibited antimicrobial activity against S. aureus, Micrococcus luteus and E. coli, with the effect increasing with CS–ZnO concentration.	Castor-oil-based polymer–CS–ZnO on artificial wounds in live rat model for 14 days: castor-oil-based polymer–CS–ZnO group healed much faster with better re-epithelialization and collagen deposition than did castor oil group and gauze group.	[108]

EGF, epidermal growth factor; PCL, polycaprolactone; CA, cellulose acetate; NHDFs, normal human dermal fibroblast; HDI, hexamethylene diisocyanate; GLA, glutaraldehyde.