School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
Department of Stomatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, P. R. China.
Biomacromolecules. 2024 Jul 8;25(7):4317-4328. doi: 10.1021/acs.biomac.4c00389. Epub 2024 Jun 3.
Despite great progress in the hydrogel hemostats and dressings, they generally lack resistant vascular bursting pressure and intrinsic bioactivity to meet arterial massive hemorrhage and proheal wounds. To address the problems, we design a kind of biomimetic and wound microenvironment-modulating PEGylated glycopolypeptide hydrogels that can be easily injected and gelled in ∼10 s. Those glycopolypeptide hydrogels have suitable tissue adhesion of ∼20 kPa, high resistant bursting pressure of ∼150 mmHg, large microporosity of ∼15 μm, and excellent biocompatibility with ∼1% hemolysis ratio and negligible inflammation. They performed better hemostasis in rat liver and rat and rabbit femoral artery bleeding models than Fibrin glue, Gauze, and other hydrogels, achieving fast arterial hemostasis of <20 s and lower blood loss of 5-13%. As confirmed by in vivo wound healing, immunofluorescent imaging, and immunohistochemical and histological analyses, the mannose-modified hydrogels could highly boost the polarization of anti-inflammatory M2 phenotype and downregulate pro-inflammatory tumor necrosis factor-α to relieve inflammation, achieving complete full-thickness healing with thick dermis, dense hair follicles, and 90% collagen deposition. Importantly, this study provides a versatile strategy to construct biomimetic glycopolypeptide hydrogels that can not only resist vascular bursting pressure for arterial massive hemorrhage but also modulate inflammatory microenvironment for wound prohealing.
尽管水凝胶止血剂和敷料取得了很大进展，但它们通常缺乏抵抗血管爆裂压力的能力和内在的生物活性，无法满足动脉大量出血和促进伤口愈合的需求。为了解决这些问题，我们设计了一种仿生和调节伤口微环境的聚乙二醇化糖肽水凝胶，它可以在大约 10 秒内轻松注射和凝胶化。这些糖肽水凝胶具有约 20 kPa 的适宜组织粘附力、约 150 mmHg 的高抗爆裂压力、约 15 μm 的大微孔率以及约 1%的溶血率和可忽略不计的炎症的优异生物相容性。它们在大鼠肝脏和大鼠和兔股动脉出血模型中的止血效果优于纤维蛋白胶、纱布和其他水凝胶，实现了<20 s 的快速动脉止血和<5-13%的低失血量。通过体内伤口愈合、免疫荧光成像以及免疫组织化学和组织学分析证实，甘露糖修饰的水凝胶可以高度促进抗炎 M2 表型的极化，并下调促炎肿瘤坏死因子-α以减轻炎症，实现完全的全层愈合，真皮增厚，毛囊密集，胶原沉积达到 90%。重要的是，这项研究提供了一种构建仿生糖肽水凝胶的通用策略，这种水凝胶不仅可以抵抗血管爆裂压力以治疗动脉大量出血，还可以调节炎症微环境以促进伤口愈合。
