Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering

Abstract

The aim of this study was to design a dermal substitute containing adipose derived stem cells (ADSC) that can be used to improve the regeneration of skin on difficult wound beds by stimulating rapid neovascularization. This was achieved by first synthesizing methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (HAMA) precursors which could be stored at -80 ^oC after lyophilisation. Polymer precursors were then dissolved in media (in 15:1 ratio), ADSCs added together with the photoinitiator and crosslinked with 40 s of UV. Hydrogels degraded by 50% over 3 weeks in an in vitro environment. ADSC loaded hydrogels could be easily handled with forceps (compressive modulus was 6 kPa). Transparency of the gel would allow a full field-of-view of a wound site. The hydrogels provided a suitable microenvironment for ADSC proliferation as shown by the filopodia observed in confocal micrographs. In vivo studies demonstrated that stem cell loaded hydrogels increased vascularization by up to 3 fold compared to their cell free counterparts. In conclusion, GelMA/HAMA hydrogels loaded with ADSC showed the desired proliferative and angiogenic properties essential to promote angiogenesis for wound healing and improving survival of tissue engineered skin.

Keywords: Adipose derived stem cells; Angiogenesis; Bicomponent hydrogel; Dermal substitute; Photocrosslinking.