MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Int J Biol Macromol. 2023 Jan 1;224:688-698. doi: 10.1016/j.ijbiomac.2022.10.157. Epub 2022 Oct 22.
Diabetic chronic wounds are not only accompanied by inflammation and ulcers but also cause amputation when they develop into severe diabetic foot. Mesenchymal stem cells (MSCs) have been proven to ameliorate diabetic wound healing, however, the low survival rate of exogenous MSCs after transplantation into the highly proteolytic wound environment is a major obstacle to effective stem cell therapy. Herein, to improve the proliferation, differentiation, and anti-apoptosis ability of transplanted MSCs, we prepared Poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with anti-inflammatory and angiogenic cytokine IL-8, then loaded the nanospheres on acellular dermal matrix to fabricate an efficient delivery medium (PLGA@IL-8/ADM) for exogenous MSCs. It was observed that, in the PLGA@IL-8-loaded ADM, MSCs presented significant proliferation and endothelial differentiation with a great survival rate. In addition, PLGA@IL-8/ADM laden with MSCs effectively induced the capillary construction, collagen deposition and wound healing in cutaneous wounds of streptozotocin-induced diabetic mice. Further immunofluorescence analysis indicated that proangiogenic factors (VEGF and α-SMA) were upregulated in regenerated tissue. Overall, our findings indicated that PLGA@IL-8/ADM-MSCs was a potential therapeutic dressing that may contribute to the therapy of diabetic wounds and the PLGA@IL-8/ADM scaffold would be a novel delivery system for exogenous cells for tissue regeneration.
糖尿病慢性伤口不仅伴有炎症和溃疡，而且当发展为严重的糖尿病足时还会导致截肢。间充质干细胞（MSCs）已被证明可改善糖尿病伤口愈合，但在外源性 MSCs 移植到高度蛋白水解的伤口环境中时，其存活率低是有效干细胞治疗的主要障碍。在此，为了提高移植 MSCs 的增殖、分化和抗凋亡能力，我们制备了包载抗炎和血管生成细胞因子 IL-8 的聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒，然后将纳米球负载在去细胞真皮基质上，构建了一种有效的外源性 MSCs 输送介质（PLGA@IL-8/ADM）。结果表明，在负载 IL-8 的 PLGA 纳米球中，MSCs 表现出明显的增殖和内皮分化，且具有很高的存活率。此外，负载 MSCs 的 PLGA@IL-8/ADM 可有效诱导链脲佐菌素诱导的糖尿病小鼠皮肤伤口中的毛细血管构建、胶原沉积和伤口愈合。进一步的免疫荧光分析表明，再生组织中促血管生成因子（VEGF 和 α-SMA）上调。总之，我们的研究结果表明，PLGA@IL-8/ADM-MSCs 是一种有潜力的治疗性敷料，可能有助于糖尿病伤口的治疗，而 PLGA@IL-8/ADM 支架将成为用于组织再生的外源性细胞的新型输送系统。
