Table 5.
Different scaffolds with angiogenic properties for wound healing and skin tissue engineering applications
| Biomaterial | Angiogenic factor/nanomaterial | Fabrication technique/method | Cross-linking | In vitro (cell type)/in vivo (animal model) | Results | Refs. |
|---|---|---|---|---|---|---|
| Collagen/Chitosan | VEGF-loaded PLGA microspheres | Freeze drying | – | In vitro (L929 mouse fibroblast) | Controlled release of VEGF; Proliferation of fibroblasts | [196] |
| Chitosan | SIKVAV peptide | Freeze dried hydrogel | – | In vivo (female C57BL/6 mice with full-thickness wound) | Re-epithelialization of wounds; Proliferation and differentiation of keratinocyte; inhibition of inflammation; Promotion of angiogenesis (increased expression of CD31) | [197] |
| Collagen/Hyaluronic acid | angiogenic growth factors (VEGF, PDGF, bFGF and EGF) | Electrospinning | EDC/NHS | In vitro (HUVECs)/In vivo (Male Sprague–Dawley diabetic rats) | Controlled release of angiogenic factors; Significant increase in HUVECs viability; Neo-vascularization (increased expression of CD31 and αSMA) | [198] |
| Hyaluronic Acid/Silk fibroin | ZnO-NPs | Electrospun Core–shell | – | In vitro (HaCat cells)/In vivo (rats with second-degree burn wounds) | Scaffolds with 3% ZnO-NPs significantly improved cell proliferation; Accelerate wound closure; Formation of new blood vessels | [199] |
| GelMA | Reduced Graphene Oxide | Freeze-dried hydrogel | UV radiation | In vitro (EA.hy926 endothelial cells, HaCat keratinocytes, and 3T3 fibroblasts)/In vivo (chicken embryo model) | No cell toxicity; Proliferation and migration of Cells; Promoted wound closure in scratch assay (wound healing assay); Increased angiogenesis in chicken embryo model | [78] |
| Chitosan/PEO | VEGF and PDGF-BB | Electrospinning | – | In vitro (HDFs)/In vivo (male Sprague–Dawley rats with full-thickness wound) | Promote the fibroblasts proliferation; Induction of angiogenesis; Epithelial regeneration; Collagen deposition and functional tissue remodeling | [200] |
| Silk fibroin/Sodium alginate | Strontium | Casting | – | In vitro (Mouse L929 fibroblasts) | Promote cell attachment and viability; Improving VEGF and bFGF secretion (induction of angiogenesis) | [201] |
| Gelatin/Sulfonated silk | basic fibroblast growth factor 2 (FGF-2) | 3D printing | EDC-NHS | In vitro (primary child foreskin fibroblasts)/in vivo (male Sprague–Dawley rats with full-thickness wounds) | Increase in proliferation of fibroblasts; constant slow-release of FGF-2; Re-vascularization; Re-epithelialization; increased expression of α-SMA and CD31 on day 28 post-surgery | [202] |
| Chitosan-PEO/PCL-Collagen | bFGF, EGF and silver sulfadiazine | Electrospinning | – | In vitro (HDFs)/In vivo (male Sprague–Dawley rats) | Higher proliferation and attachment of fibroblasts; re-epithelialization; increased angiogenesis; decrease in inflammatory cells | [203] |
| Chitosan/PVA | NO | Freeze dried hydrogel | TEOS 2% | In vitro (HaCaT keratinocytes cells and 3T3 fibroblast cells) | Prolonged and sustained release of NO. Increased cell viability and proliferation | [204] |
| PCL | Y2O3-NPs | Electrospinning | – | In vitro (Mouse L-929 fibroblast)/In vivo (male Sprague–Dawley rats) | Proliferation of L-929 fibroblast; Increased expression of VEGF, EGFR (increased angiogenesis), downregulation of TNF-α, and COX-2 (Cycloxygenase-2) (decreased inflammation) | [79] |
| PCL | Europium hydroxide nanorods | Electrospinning | – | In vitro (HUVECs) | No aggregation of blood cells (RBC, WBC and platelets); enhanced adhesion, viability and proliferation of HUVECs; increased phosphorylation of Akt protein; increased expression of VEGFR2 | [162] |
| PCL | ZnO-NPs | Electrospinning | – | In vitro (HDFs)/in vivo (guinea pigs with full-thickness skin wounds) | promoted proliferation HDFs on the PCL/ZnO-NPs scaffold; Increased expression of FGF2 and VEGF-A; Complete wound healing on 25th day of study | [12, 106] |
| PCL | Titanium Nanorods | Electrospun mesh | – |
In vitro (Mouse 3T3 fibroblasts and immortalized human HaCat Keratinocytes, HOECs), Scratch test, CAM Angiogenesis Assay/In vivo (Guinea Pigs, male Sprague–Dawley rats with full-thickness excision wounds) |
Cell compatibility, adhesion and proliferation; Migration and proliferation of 3T3 cells and HaCat keratinocytes into the scratched area; Appearance of network of blood vessels growing around the scaffold Promote angiogenesis after subcutaneous implantation in Guinea pigs; Effective reduction in the wound size after 16 days in rats with full-thickness wounds |
[78] |
| PHBV | CeO2-NPs | Electrospinning | – | In vitro (HOECs and HMECs); HaCat cells in scratch assay; CAM angiogenesis assay/In vivo (Male Sprague–Dawley diabetic rats with full thickness excision wounds) | Enhanced cell viability and adhesion of HOEC and HMEC; Migration of HaCat cells into the scratched area; Formation of blood vessels near the scaffold; Healing of full thickness excision wounds during 15 days of study | [205] |
| PCL/Gelatin | MgO | Electrospinning | – | In vitro (hEnSCs)/In vivo (male Wistar rats with full-thickness wounds) | Increased proliferation of hEnSCs; Promote wound area closure; increase in number of vascular structures | [206] |
| PLA-PVA | CTGF | Electrospun Core–Shell Membrane | – |
In vitro (3T3 fibroblasts, HaCat Keratinocytes, EA.hy926 endothelial cells); In vitro wound healing assay (scratch); CAM assay |
Higher fibroblast, keratinocyte and endothelial cell viability; Promote wound area closure in scratch test; Induction of angiogenesis in CAM model | [207] |
| PU-PDMS/Fibrin | PLGA nanoparticles loaded with VEGF and bFGF | Spray phase-inversion technique | – | In vivo (diabetic mice with full-thickness skin wounds) | accelerated wound closure at day 15 post-surgery; Complete re-epithelialization; Formation of new blood vessels | [208] |
| PVA/Chitosan/Gelatin | bFGF-loaded PCL microspheres | Freeze-dried hydrogels | – | In vitro (human fibroblast cells)/in vivo (male Wistar rats with full-thickness skin wounds) | Sustained release of bFGF; Adhesion and proliferation of human fibroblast cells on the surface of the hydrogel; Re-epithelialization, Enhanced angiogenesis after 20 days of treatment | [209] |
PLGA poly (lactic-co-glycolic acid, SIKVAV Ser-Ile-Lys-Val-Ala-Val, EDC/NHS ethyl (dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide, HUVECs human umbilical vein endothelial cell, αSMA α-smooth muscle actin, GelMA gelatin-methacryloyl, PEO poly (ethylene oxide), HDFs human dermal fibroblasts, PCL polycaprolactone, EGF epidermal growth factor, PVA poly (vinyl alcohol), TEOS tetraethoxysilane, NO nitric oxide, COX-2 cycloxygenase-2, RBC red blood cell, WBC white blood cell, HOECs oral epithelial cells, CAM chorioallantoic membrane, HMECs human mammary epithelial cells, MgO magnesium oxide, hEnSCs human endometrial stem cells, Y2O3-NPs Yttrium oxide nanoparticle, PHBV poly (3-hydroxybutyrate-co-3-hydroxyvalerate), CeO2-NPs cerium oxide nanoparticle, PLA poly lactic acid, PU poly (ether)urethane, PDMS polydimethylsiloxane, CTGF connective-tissue growth factor