Delivery of adipose-derived growth factors from heparinized adipose acellular matrix accelerates wound healing

Dermal white adipocytes are closely associated with skin homeostasis and wound healing. However, it has not been fully investigated whether adipose-derived products improve wound healing. Here, we obtained adipose acellular matrix (AAM) and adipose-derived growth factors (ADGFs) from human adipose tissue and fabricated an ADGF-loaded AAM via surface modification with heparin. The product, HEP-ADGF-AAM, contained an adipose-derived scaffold and released ADGFs in a controlled fashion. To test its efficacy in promoting wound healing, mice with full thickness wound received three different treatments: HEP-ADGF-AAM, AAM and ADM. Control mice received no further treatments. Among these treatments, HEP-ADGF-AAM best improved wound healing. It induced adipogenesis in situ after in vivo implantation and provided an adipogenic microenvironment for wounds by releasing ADGFs. HEP-ADGF-AAM not only induced adipocyte regeneration, but also enhanced fibroblast migration, promoted vessel formation, accelerated wound closure, and enhanced wound epithelialization. Moreover, there was a close interaction between HEP-ADGF-AAM and the wound bed, and collagen was turned over in HEP-ADGF-AAM. These results show that HEP-ADGF-AAM might substantially improve re-epithelialization, angiogenesis, and skin appendage regeneration, and is thus a promising therapeutic biomaterial for skin wound healing.