A biotin-stabilized HKUST-1/ADM scaffold for facilitating MSC endothelial differentiation and vascularization in diabetic wound healing

Abstract

Inadequate angiogenesis in diabetic wound healing has been identified as one of the most difficult issues to treat. Copper ions (Cu²⁺) have been confirmed to stimulate angiogenesis; nevertheless, the rapid rise in non-physiological Cu²⁺ concentrations increases the danger of ion poisoning. For the first time, biotin was used to stabilize a copper-based metal–organic framework (HKUST-1) to change its hydrophobicity and achieve sustained release of Cu²⁺. The inability to offer a suitable area for the dynamic interaction between cells and growth factors still restricts the use of nanomaterials for the regeneration of injured skin in diabetes. Acellular dermal matrix (ADM) scaffolds are collagen fibers with natural spatial tissue that can create a biological “niche” for cell attachment and growth. In this study, biotin-stabilized HKUST-1 (B-HKUST-1) nanoparticles were modified with an ADM to form a novel scaffold (ADM–B-HKUST-1). Notably, Cu²⁺ and mesenchymal stem cells (MSCs) released by the composite scaffold may synergistically promote MSC adhesion, proliferation and endothelial differentiation by upregulating the expression of transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Overall, the ADM–B-HKUST1 scaffold combines the dual advantages of the sustained release of Cu²⁺ and creating a biological “niche” can provide a potential strategy for enhancing angiogenesis and promoting diabetic wound healing.