Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
ACS Biomater Sci Eng. 2023 Mar 13;9(3):1496-1509. doi: 10.1021/acsbiomaterials.2c01110. Epub 2023 Feb 23.
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 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.
糖尿病患者有 15-25%的机会患上糖尿病足溃疡，这是一种严重的并发症，也是临床医生面临的巨大挑战。糖尿病足溃疡的传统治疗方法是通过手术切除坏死皮肤，清洁伤口，并用皮瓣覆盖。然而，皮瓣的效果往往有限，而且获取皮瓣需要进行第二次手术，这可能会给患者带来额外的风险。皮肤组织工程为糖尿病足溃疡带来了新的解决方案。在此，我们通过复合培养和优化的去细胞化策略开发了一种生物活性贴片。该贴片由猪小肠黏膜下层（SIS）制备，并通过源自尿液来源的干细胞（USCs）的细胞外基质（ECM）进行修饰，既保留了促血管生成和组织再生的细胞因子，又具有低免疫原性。该方案包括优化去细胞化时间和建立方法。此外，我们还研究了贴片的伤口愈合能力的机制，并通过 I 型糖尿病大鼠的抗收缩全层皮肤缺损模型评估了其用于皮肤伤口愈合的可行性。结果表明，该贴片与负载 USCs 的 SIS 具有相当的效果。我们的研究结果表明，这种优化的去细胞化方案可能为需要去除细胞物质的细胞负载支架提供一种策略，同时保留 ECM 中足够的生物活性成分，以用于进一步的应用。
