Synergistic Angiogenesis Promoting Effects of Extracellular Matrix Scaffolds and Adipose-Derived Stem Cells During Wound Repair

Slow vascularization rate is considered one of the main drawbacks of scaffolds used in wound healing. Several efforts, including cellular and acellular technologies, have been made to induce vascular growth in scaffolds. However, thus far, there is no established technology for inducing vascular growth. The aim of this study was to promote the vascularization capacities of scaffolds by seeding adipose-derived stem cells (ADSCs) on them and to compare the vascularization capacities of different scaffolds seeded with ADSCs. Two kinds of extracellular matrix scaffolds (small intestinal submucosa [SIS] and acellular dermal matrix [ADM]) and a kind of composite scaffold (collagen-chondroitin sulfate-hyaluronic acid [Co-CS-HA]) were selected. Subcutaneous implantation analysis showed that the vascularization capacity of SIS and ADM was greater than that of Co-CS-HA. ADSCs seeded in SIS and ADM secreted greater amounts of vascular endothelial growth factor than those seeded in Co-CS-HA. In a murine skin injury model, ADSC-seeded scaffolds enhanced the angiogenesis and wound healing rate compared with the nonseeded scaffolds. Moreover, ADSC-SIS and ADSC-ADM had greater vascularization capacity than that of ADSC-Co-CS-HA. Taken together, these results suggest that ADSCs could be used as a cell source to promote the vascularization capacities of scaffolds. The vascularization capacities of ADSC-seeded scaffolds were influenced by both the vascularization capacities of the scaffolds themselves and their effects on the angiogenic potential of ADSCs; the combination of extracellular matrix scaffolds and ADSCs exhibited synergistic angiogenesis promoting effects.