Fabrication of an Adhesive Small Intestinal Submucosa Acellular Matrix Hydrogel for Accelerating Diabetic Wound Healing

The treatment of diabetic skin defects comes with enormous challenges in the clinic due to the disordered metabolic microenvironment. In this study, we therefore designed a novel composite hydrogel (SISAM@HN) with bioactive factors and tissue adhesive properties for accelerating chronic diabetic wound healing. Hyaluronic acid (HA) modified by N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide (NB) held the phototriggering tissue adhesive capacity. Decellularized small intestinal submucosa (SIS) was degreased and digested to form the acellular matrix, which facilitated bioactive factor release. The results of the burst pressure test demonstrated that the in situ formed hydrogel possessed a tissue adhesive property. In vitro experiments, based on bone marrow stromal cells, revealed that the SIS acellular matrix-containing hydrogel contributed to promoting cell proliferation. In vivo, a diabetic mouse model was created and used to evaluate the tissue regeneration function of the obtained hydrogel, and our results showed that the synthesized hydrogel could assist collagen deposition, attenuate inflammation, and foster vascular growth during the wound healing process. Overall, the SIS acellular matrix-containing HA hydrogel was able to adhere to the wound sites, promote cell proliferation, and facilitate angiogenesis, which would be a promising biomaterial for wound dressing in clinical therapy of diabetic skin defects.