Table 5 Different scaffolds with angiogenic properties for wound healing and skin tissue engineering applications

Collagen/Chitosan

VEGF-loaded PLGA microspheres

Freeze drying

–

In vitro (L929 mouse fibroblast)

Controlled release of VEGF; Proliferation of fibroblasts

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)

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)

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

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

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

Silk fibroin/Sodium alginate

Strontium

Casting

–

In vitro (Mouse L929 fibroblasts)

Promote cell attachment and viability; Improving VEGF and bFGF secretion (induction of angiogenesis)

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

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

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

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)

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

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 25^th 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

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

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

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

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

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