Table 5.
Combination therapies evaluated for cutaneous wound and scarring indications
| Biomaterial(s) | Fabrication Method(s) | Treatment(s) | Experimental Parameters Tested and Outcomes |
|---|---|---|---|
| Chitosan | |||
| Hydrogel | PDGF-ββ+VEGF-A | Rat full-thickness incisional wound model (sutured)—single treatment led to oxidative changes relative to hydrogel and untreated controls164 | |
| PAAm | Hydrogel | EGF+Piperacillin | In vitro release—antibiotic within 10 h, EGF cumulative over 10 days, increase in fibroblast proliferation157 |
| PEG | Scaffold | FGF-2+VEGF-A+heparin |
In vitro culture—keratinocyte proliferation and migration Rat full-thickness excisional wound model—single treatment led to faster healing relative to scaffold control138 |
| HA+PLGA | Hydrogel+microsphere | VEGF-A+vancomycin |
In vitro release—antibiotic and VEGF cumulative over 7 and 20 days Infected rat full-thickness splinted excisional wound model—single treatment led to faster healing, with increased granulation tissue relative to hydrogel, hydrogel+antibiotic and hydrogel+VEGF microsphere controls158 |
| PEO+PLGA | Nanofiber+NP | PDGF-ββ+VEGF-A |
In vitro release—VEGF-A in 24 h, PDGF-ββ 40% by 7.5 days, In vitro culture—supported fibroblast proliferation Rat full-thickness excisional wound model—single treatment led to faster healing relative to fiber control135 |
| Alginate | |||
| Microparticle | FGF-2+Rifamycin |
In vitro release in serum—induced fibroblast proliferation and migration Rat full-thickness excisional wound model—single treatment led to faster healing than untreated control98 |
|
| Collagen | |||
| Membrane | FGF-2+FGF-7 |
In vitro release—cumulative over 28 days Rat full-thickness splinted excisional wound model—single treatment led to faster healing relative to membrane, membrane+FGF-2 or FGF-7 controls155 |
|
| HA | Hydrogel | VEGF-E+vIL-10 | Horse bandaged full-thickness excisional limb wound model—single treatment led to faster repair processes and resolution of EGT formation relative to hydrogel control170 |
| HA+gelatin | Nanofiber+NP | EGF+FGF-2 PDGF-ββ+VEGF-A |
In vitro release—within 5 days for FGF-2 and cumulative over 25 days for others In vitro culture—supports endothelial tube formation STZ-induced diabetic rat full-thickness excisional wound model—single treatment led to faster healing relative to nanofibers, nanofibers+FGF-2/EGF controls126 |
| Fibrin | |||
| Matrix | EGF+keratinocytes |
In vitro release—burst within 24 h, cumulative over 7 days Mouse full-thickness excisional wound model—single treatment led to faster healing relative to keratinocytes+matrix, EGF+matrix and matrix controls117 |
|
| Sealant | PDGF-ββ+fibroblasts | Rabbit full-thickness excisional wound model—single treatment led to faster healing relative to sealant and sealant+fibroblasts controls116 | |
| Fibrinogen fragments | Matrix | VEGF-A+PDGF-ββ |
In vitro culture—supports tubule formation by endothelial cells or sprout formation by smooth muscle cells Diabetic db/db mouse full-thickness excisional wound model—single treatment led to faster healing relative to matrix, matrix+FN and matrix+GF controls161 |
| HBD+PEG | Matrix | Factor XIIIa substrate+FGF-2+PlGF |
In vitro release+plasmin—burst release within 24 h, retention over 7 days Diabetic db/db mouse full-thickness excisional wound model—single treatment led to faster healing with fibrin+GFs and PEG+HBD+GFs relative to matrix, matrix+FGF-2 or PlGF controls137 |
| Collagen | Sealant+matrix | FGF-2+VEGF-A |
In vitro release—within 24 h, cumulative over 8 days Mouse full-thickness excisional wound model—single treatment led to prolonged vascularization relative to matrix+GFs, matrix+sealant and matrix controls156 |
| PEtU-PDMS+PLGA | Scaffold+NP | FGF-2+VEGF-A+heparin | Diabetic db/db mouse full-thickness excisional wound model—single treatment led to faster healing relative to scaffold, scaffold+GFs and scaffold with NP controls127 |
EGT, exuberant granulation tissue formation; HBD, heparin-binding domain; PAAm, polyacrylamide; PDMS, polydimethylsiloxane; PEG, poly(ethylene glycol); PEO, poly(ethylene oxide); PEtU, polyetherurethane; PLGA, poly(lactic-co-glycolic acid); PlGF, placental growth factor; STZ, streptozotocin.