PDF(Pubmed)
Abstract：
Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.
摘要：
慢性糖尿病伤口是重要的医疗保健挑战。高浓度葡萄糖，高水平的基质金属蛋白酶-9（MMP-9），和长期炎症构成了糖尿病伤口的特殊伤口环境。组织坏死加重不规则伤口的形成。上述所有因素都阻碍了慢性糖尿病伤口的愈合。为了解决这些问题,设计了一种葡萄糖和MMP-9双响应温度敏感形状自适应水凝胶（CBP/GMs@Cel＆INS），并用聚乙烯醇（PVA）和壳聚糖接枝苯硼酸（CS-BA）通过封装胰岛素（INS）和含有塞来昔布（GMs@Cel）的明胶微球。温度敏感的自适应CBP/GMs@Cel&INS提供了一种平衡流体样移动性的新方法(快速适应深层伤口，大约37°C）和固体状弹性（保护伤口免受外力，大约25°C)的自适应水凝胶，同时在高水平葡萄糖和MMP-9的环境中按需释放胰岛素和塞来昔布。此外，CBP/GM@Cel&INS表现出重塑和自我修复特性，增强的粘合强度(39.65±6.58kPa)，下调MMP-9，促进细胞增殖，迁移,和葡萄糖消耗。在糖尿病全层皮肤缺损模型中，CBP/GMs@Cel&INS可显着缓解炎症，调节伤口局部高水平葡萄糖和MMP-9，并通过温度敏感形状适应性特征和双反应系统的协同作用有效促进伤口愈合。
