Fan Xianmou, Su Zhihong, Zhang Wanjun, Huang Haili, He Chengzhang, Wu Zeyong, Zhang Peihua
Department of Plastic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China.
Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Zhanjiang, 524000, China.
Mater Today Bio. 2024 Nov 22;29:101361. doi: 10.1016/j.mtbio.2024.101361. eCollection 2024 Dec.
Promoting wound nerve regeneration and synchronously initiating angiogenesis are critical factors in the healing process of diabetic wounds. However, existing research on diabetic wounds mainly focuses on angiogenesis, bacterial infection and reactive oxygen species, often failing to coordinate neurogenesis and angiogenesis. To coordinate the symbiosis of nerves and blood vessels in the diabetic wounds, we successfully designed a multifunctional chitosan (CS)-based sponges by regulating the structure of CS specifically for diabetic wound healing. This sponge, which facilitates effective exudate transfer and modulates the wound microenvironment, was constructed using hydroxybutyl CS grafted with thioctic acid (TA), named as HCT sponge. When applied in a humid environment, the hydrophobic side chains of the HCT sponge interact with self-assembled hydrophobic domains, forming gel-sponge composite. Experimental results showed that the adhesion strength of the HCT sponge to wet porcine skin was 70.3 kPa. Additionally, the sponge exhibited favorable degradability, cytocompatibility and antioxidant properties. As it is shown in the experiments in vitro, sponge can not only promote cell proliferation, migration, and blood vessel formation, but also promote M2 macrophage polarization. Moreover, the rat liver and femoral artery injury model validated that the HCT sponge can effectively treat heavy bleeding from wounds efficacy through quickly sealing wounds and the formation of multiple hemostatic dams. In vivo studies indicated that the HCT sponge significantly accelerated the diabetic wound healing process compared to the recombinant bovine basic fibroblast growth factor gel, achieving a better recovery from the HCT sponge after 15 days. Pathological results show that the designed novel sponge holds considerable promise for treating diabetic wound, allowing regenerative neurogenesis and angiogenesis at the wound site, which provides a significant potential for further improving clinical applications.
促进伤口神经再生并同步启动血管生成是糖尿病伤口愈合过程中的关键因素。然而，现有关于糖尿病伤口的研究主要集中在血管生成、细菌感染和活性氧物种上，常常未能协调神经发生和血管生成。为了协调糖尿病伤口中神经和血管的共生，我们通过专门针对糖尿病伤口愈合调节壳聚糖（CS）的结构，成功设计了一种基于多功能CS的海绵。这种海绵有助于有效引流渗出液并调节伤口微环境，它是用接枝硫辛酸（TA）的羟丁基CS构建的，命名为HCT海绵。当在潮湿环境中应用时，HCT海绵的疏水侧链与自组装的疏水结构域相互作用，形成凝胶-海绵复合材料。实验结果表明，HCT海绵对湿猪皮的粘附强度为70.3 kPa。此外，该海绵具有良好的降解性、细胞相容性和抗氧化性能。体外实验表明，该海绵不仅能促进细胞增殖、迁移和血管形成，还能促进M2巨噬细胞极化。此外，大鼠肝和股动脉损伤模型证实，HCT海绵可通过快速封闭伤口和形成多个止血屏障，有效治疗伤口严重出血。体内研究表明，与重组牛碱性成纤维细胞生长因子凝胶相比，HCT海绵显著加速了糖尿病伤口的愈合过程，15天后从HCT海绵获得了更好的恢复。病理结果表明，所设计的新型海绵在治疗糖尿病伤口方面具有很大的潜力，能够在伤口部位实现再生性神经发生和血管生成，这为进一步改善临床应用提供了巨大潜力。
