Application of polydopamine coated silk fibroin methacryloyl hydrogel loaded with cell free fat extract in diabetic wound healing.

Abstract

Diabetic foot ulcers (DFUs) are common and serious problems in diabetes patients. They also represent one of the leading causes of non-traumatic lower limb amputation worldwide. Despite improvements in clinical care, numerous standard therapies fail to completely close chronic diabetic wounds. Cell-free fat extract (Ceffe) aids tissue repair and angiogenesis but its clinical worth is greatly reduced by rapid diffusion and enzymatic degradation in the wound. Silk fibroin methacryloyl (SilMA) can be formulated into a photocrosslinked hydrogel capable of sustained delivery of bioactive factors, whereas polydopamine (pDA) provides durable wet-tissue adhesion. In this work, we developed a multifunctional composite hydrogel pSilMA@Ceffe (polydopamine-coated SilMA hydrogel loaded with Ceffe) that integrates the prolonged release properties of SilMA with the tissue-binding strength of pDA to enhance healing of refractory diabetic wounds. We prepared and characterized pSilMA@Ceffe with respect to physicochemical properties, printability, and release kinetics. Cellular assays and diabetic mouse models employed used to assess biocompatibility. Cell proliferation, migration, and tube formation were evaluated using in vitro assays, while full-thickness skin wounds in db/db mice were used to determine in vivo efficacy. Wound closure was monitored at multiple time points, and tissue regeneration was assessed via H&E, Masson's trichrome, and immunofluorescent staining for CD31, keratin 1 (K1), Ki-67, and type I collagen (Col-1). The final hydrogel had satisfactory 3D printability, stable tissue adhesion, and constant long-term release of Ceffe. It supported cell survival and significantly enhanced proliferation, migration, and angiogenic activity in culture. In diabetic mice, pSilMA@Ceffe accelerated wound healing, neovascularization, and cell proliferation, and promoted more organized collagen deposition in the regenerating dermis. Combining photocrosslinkable handling with robust pro-regenerative activity, pSilMA@Ceffe represents an effective and translatable candidate for the clinical treatment of chronic diabetic wounds.