PDF(Pubmed)
Abstract：
Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1-3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3-7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.
摘要：
糖尿病伤口愈合是一项重要的临床挑战，因为伤口中的异常免疫细胞会引起慢性炎症并损害组织再生。因此,调节巨噬细胞的行为和功能可能有助于改善糖尿病伤口的治疗结果。在这里，基于胶原蛋白和丝素蛋白，构建了具有良好排列层和高孔隙率的含硫酸化壳聚糖（26SCS-SilMA/Col-330）的复合海绵（26SCS-SilMA/Col-330），旨在诱导适当的炎症反应并促进血管生成。结果表明，复合海绵的有序拓扑结构可以在早期引发Mφs的促炎反应。早期和中期快速释放26SCS（浓度范围为1-3mg/mL）引起积极的炎症反应；在3天内引发Mφs的促炎反应；在3-7天内将M1Mφs转移到M2表型；并显着上调两种典型的血管生成生长因子的表达，即VEGF和PDGF-BB，在第7天,导致快速的HUVEC迁移和血管生成。体内数据还表明，在手术后的第14天，26SCS-SilMA/Col-330植入区域表现出较少的炎症，更快的再上皮化，更丰富的胶原蛋白沉积和更多的血管在皮肤组织。具有较高26SCS含量的复合海绵（（5.0）26SCS-SilMA/Col-330和（7.5）26SCS-SilMA/Col-330）可以更好地协调Mφs的表型和功能，并促进伤口愈合。这些发现突出表明，在这项工作中开发的26SCS-SilMA/Col-330海绵可能具有作为治疗糖尿病伤口的新型敷料的巨大潜力。
