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

Abstract

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.

Therapeutic Benefits of Stem Cells and Exosomes for Sulfur-Mustard-Induced Tissue Damage

“…Some potential future directions for this area of research include: (i) identification of optimal cell sources: different types of stem cells may have varying regenerative potential and safety profiles in the context of SM-induced tissue injury. Further research is needed to identify the optimal cell sources for this condition, such as using urine-derived stem cells obtained from patients using non-invasive methods [ 51 , 89 , 90 , 91 ]. (ii) Development of personalized therapies: there may be individual differences in response to stem cell and exosome therapies.…”

Preclinical Evaluation of Bioactive Small Intestinal Submucosa-PMMA Bone Cement for Vertebral Augmentation

“…It has been approved by the FDA, and the xenogenically derived SIS has been widely used in various tissue repair studies. Furthermore, in vivo has indicated that it is nonimmunogenic. − Several studies have verified that SIS can provide a good microenvironment to facilitate the proliferation, attachment, and osteogenic differentiation of fibroblast bone, osteoblasts, and marrow mesenchymal stem cells. ,− In our previous study, SIS was applied to modify commercially available PMMA cement to optimize the biological performance and in vivo repair effect of the basic material . Though PMMA with 20 or 40% SIS powder showed excellent bioactivity to enhance the new bone formation, the compressive strength of the constructs was hard to meet the requirement of clinical application (ISO5833), which was essential for clinical application.…”