Quickly promoting angiogenesis by using a DFO-loaded photo-crosslinked gelatin hydrogel for diabetic skin regeneration

Abstract

Changes in blood vessel formation, especially microvasculature formation, are one of the most important factors contributing to the poor wound healing capabilities of diabetic patients. Furthermore, recovery of the vascular network in the early stages after injury is a key factor in the prevention of wound expansion and ulcer formation. A hydrogel is a popular scaffold type and has many biological advantages, however, it is incapable of rapidly recruiting angiogenesis-related cells and cytokines to the wound area under the disturbed microcirculatory conditions of diabetics. For the above reasons, we devised a desferrioxamine (DFO)-loaded photo-crosslinked hydrogel (gelatin methacrylamide (Gelma)) for quickly developing the vascular network and accelerating skin reconstruction. The controlled release of DFO peaking at 16 h followed by a steady release after 48 h through the swelling of the Gelma hydrogel led to a significant increase of neovascularization. The in vitro results showed that DFO–Gelma provided an excellent microenvironment for cell viability, adhesion and proliferation, and up-regulated the expression of HIF-1α, which was critical for blood vessel formation. The in vivo studies showed new blood vessels, high quality granulation tissues, and early epithelialization in wound beds by treating them with DFO-loaded hydrogels. Through this investigation, the mechanism associated with wound healing was further investigated. This study demonstrated that DFO–Gelma was safe, reliable, and highly effective for the diabetic wound healing process.