Three-dimensional cultivation of human adipose-derived stem cells with human decellularized adipose tissue matrix scaffold promotes diabetic wound healing

Abstract

Diabetic wounds are a worldwide health problem, with increasing morbidity and risk of amputation. This study investigated a novel application of a human decellularized adipose tissue matrix (hDAM) as a natural 3D scaffold for delivering human adipose-derived stem cells (hASCs) to diabetic wounds. The porous structure, ability to preserve extracellular matrix components, and convenient storage conditions of decellularized hDAM make it a potential clinical wound dressing material. The hASCs cultured in the hDAM scaffold exhibited a fibroblast-like morphology and more evenly distributed cells on both the surface and inside the porous structure of the hDAM scaffold. In addition, the biocompatibility of hDAM enhanced the hASCs proliferation, maintenance of the stemness properties, and release of angiogenic cytokines compared to those under standard culture conditions. Moreover, cell suspensions derived from hASCs cultured in hDAM scaffolds promoted the proliferation and migration of human umbilical vascular endothelial cells, indicating its potential effect in promoting angiogenesis. Furthermore, the potential clinical therapeutic efficacy of the hASC-hDAM composite for diabetic wound healing was evaluated using a full-thickness wound model in diabetic mice. Diabetic rats treated with the hASCs-seeded hDAM scaffold displayed enhanced wound healing efficiency, including an improved blood perfusion volume for wounds, reduced number of inflammatory cells, and enhanced epithelization. This study demonstrated that the 3D model that combined hASCs and an hDAM could accelerate wound healing and might hold potential for clinical application to enhance diabetic wound healing and regeneration.