Jia Yile, Zhang Xianhui, Yang Weihu, Lin Chuanchuan, Tao Bailong, Deng Zhiwen, Gao Pengfei, Yang Yulu, Cai Kaiyong
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
J Mater Chem B. 2022 Apr 13;10(15):2875-2888. doi: 10.1039/d2tb00064d.
Diabetes is a universal disease in the world. In the wounds of diabetic individuals, chronic inflammation and an inefficient fibrogenic process hinder the formation and deposition of the ECM, which delays the process of wound healing. To reconstruct the ECM of a diabetic patient's wound, in this work, we designed a pH-responsive "Double H-bonds" (hydrogen bond and hydrazone bond) hyaluronic acid-collagen hydrogel. This hydrogel can be self-gelled quickly in neutral and alkaline environments. But the weakly acidic inflammatory environment of diabetic wounds may accelerate the degradation of the hydrogel and the release of metformin. The results showed that the hydrogel can enhance the adhesion and infiltration of fibroblasts while inhibiting the growth of macrophages. Meanwhile, metformin could be released and polarize macrophages from M1 to M2, thereby accelerating the migration of fibroblasts and the production of collagen in a high glucose environment. The results proved that this hydrogel could remodel the ECM in diabetic mice wounds.
糖尿病是一种全球性疾病。在糖尿病患者的伤口中，慢性炎症和低效的纤维生成过程会阻碍细胞外基质（ECM）的形成和沉积，从而延缓伤口愈合进程。为了重建糖尿病患者伤口的ECM，在本研究中，我们设计了一种pH响应性的“双氢键”（氢键和腙键）透明质酸 - 胶原蛋白水凝胶。这种水凝胶能在中性和碱性环境中快速自凝胶化。但糖尿病伤口的弱酸性炎症环境可能会加速水凝胶的降解以及二甲双胍的释放。结果表明，该水凝胶可增强成纤维细胞的黏附与浸润，同时抑制巨噬细胞的生长。与此同时，二甲双胍能够释放并使巨噬细胞从M1型极化至M2型，从而在高糖环境中加速成纤维细胞的迁移和胶原蛋白的产生。结果证明，这种水凝胶能够重塑糖尿病小鼠伤口的ECM。
