Bioactive ECM-Loaded SIS Generated by the Optimized Decellularization Process Exhibits Skin Wound Healing Ability in Type I Diabetic Rats.

Patients with diabetes have 15-25% chance for developing diabetic ulcers as a severe complication and formidable challenge for clinicians. Conventional treatment for diabetic ulcers is to surgically remove the necrotic skin, clean the wound, and cover it with skin flaps. However, skin flap often has a limited efficacy, and its acquisition requires a second surgery, which may bring additional risk for the patient. Skin tissue engineering has brought a new solution for diabetic ulcers. Herein, we have developed a bioactive patch through a compound culture and the optimized decellularization strategy. The patch was prepared from porcine small intestinal submucosa (SIS) and modified by an extracellular matrix (ECM) derived from urine-derived stem cells (USCs), which have low immunogenicity while retaining cytokines for angiogenesis and tissue regeneration. The protocol included the optimization of the decellularization time and the establishment of the methods. Furthermore, the in vitro mechanism of wound healing ability of the patch was investigated, and its feasibility for skin wound healing was assessed through an antishrinkage full-thickness skin defect model in type I diabetic rats. As shown, the patch displayed comparable effectiveness to the USCs-loaded SIS. Our findings suggested that this optimized decellularization protocol may provide a strategy for cell-loaded scaffolds that require the removal of cellular material while retaining sufficient bioactive components in the ECM for further applications.