Zwitterionic poly(sulfobetaine methacrylate) hydrogels with optimal mechanical properties for improving wound healing in vivo
Zwitterionic poly(sulfobetaine methacrylate) hydrogels with optimal mechanical properties for improving wound healing in vivo
复制标题
具有最佳机械性能的两性离子聚（磺基甜菜碱甲基丙烯酸酯）水凝胶可改善体内伤口愈合
DOI：
10.1039/c8tb02590h
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发表时间：
2019-03-14
影响因子：
7
通讯作者：
Wu, Jiang
中科院分区：
文献类型：
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作者：
He, Huacheng;Xiao, Zecong;Wu, Jiang
两性离子水凝胶由于其独特的防污性能和力学性能，被认为是一种很有前途的伤口敷料材料。虽然两性离子水凝胶的粘弹性和柔软性在理论上对于创造适应性细胞壁龛是必不可少的，但潜在的机械调节伤口愈合机制仍然难以捉摸。为了验证这一假设，我们在不同交联剂含量下制备了具有不同弹性模量的两性离子聚甲基丙烯酸亚砜甜菜碱（polySBMA）水凝胶，并将其应用于小鼠全层皮肤创面。体内伤口愈合研究比较了软性和硬性聚bma水凝胶对伤口愈合率、肉芽组织形成和胶原沉积的机械诱导作用。整体结果显示，更软、更粘弹性的水凝胶促进细胞增殖、肉芽形成、胶原聚集和软骨性ECM沉积。较软的水凝胶具有如此高的创面愈合效率，可能是由于通过扩大细胞增殖来耗散应力，上调血管形成，增强M2/M1巨噬细胞的极化，为细胞增殖和迁移提供更多的氧气和营养，从而增强创面修复。这项工作不仅揭示了两性离子聚bma水凝胶的力学性能与伤口愈合的关系，而且为下一代伤口敷料提供了有前途的候选材料和策略。
Zwitterionic hydrogels, as highly hydrated and soft materials, have been considered as promising materials for wound dressing, due to their unique antifouling and mechanical properties. While the viscoelasticity and softness of zwitterionic hydrogels are hypothetically essential for creating adaptive cellular niches, the underlying mechanically regulated wound healing mechanism still remains elusive. To test this hypothesis, we fabricated zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogels with different elastic moduli prepared at different crosslinker contents, and then applied the hydrogels to full-thickness cutaneous wounds in mice. In vivo wound healing studies compared the mechanical cue-induced effects of soft and stiff polySBMA hydrogels on wound closure rates, granulation tissue formation and collagen deposition. Collective results showed that the softer and more viscoelastic hydrogels facilitated cell proliferation, granulation formation, collagen aggregation, and chondrogenic ECM deposition. Such high wound healing efficiency by the softer hydrogels is likely attributed to stress dissipation by expanding the cell proliferation, the up-regulation of blood vessel formation, and the enhanced polarization of M2/M1 macrophages, both of which would provide more oxygen and nutrients for cell proliferation and migration, leading to enhanced wound repair. This work not only reveals a mechanical property-wound healing relationship of zwitterionic polySBMA hydrogels, but also provides a promising candidate and strategy for the next-generation of wound dressings.