Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds.

Significance

Development of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.

中文翻译：

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硫酸盐两性离子聚甲基丙烯酸甜菜碱酯水凝胶促进皮肤完全再生

皮肤伤口的愈合仍然是一个历史悠久的挑战性问题，并受到异物反应的阻碍，其中包括严重的炎症反应，不良的新血管形成，不完全的上皮再形成和有缺陷的ECM重塑。与特定药物或生长因子结合的生物相容性聚合物的开发已被视为治疗皮肤伤口的一种有前途的策略。为了开发用于伤口愈合的基于聚（乙二醇）PEG的聚合物，已经进行了重大的研究工作，但是对两性离子材料的研究却很少，其中一些已经证明了它们在体外的超低污垢性和抗炎性。体内。在这里，我们合成了超低污染的两性离子硫酸化的聚甲基丙烯酸磺基甜菜碱（polySBMA）水凝胶，并将其应用于小鼠的全层皮肤伤口。通过体内组织学评估了SBMA水凝胶对伤口愈合过程中伤口闭合，再上皮比率，ECM重塑，血管生成和巨噬细胞反应的愈合作用。实验。集体结果表明，SBMA水凝胶可通过增强血管生成，降低炎症反应和调节巨噬细胞极化来促进小鼠全层切除急性伤口再生。一致地，与纯PEG水凝胶相比，将SBMA掺入P​​EG水凝胶还改善了总体伤口愈合效率。这项工作证明了两性离子SBMA水凝胶是用于治疗全层皮肤切除伤口的有前途的伤口敷料。

意义

高效伤口再生系统的开发对于生物医学应用实际上很重要。在这里，我们合成了超低污染的两性离子硫酸盐化的聚甲基丙烯酸磺基甜菜碱（polySBMA）水凝胶，并将其应用于小鼠的全层皮肤伤口，与之相比，PEG水凝胶作为对照。我们是第一个使用全厚度切除小鼠模型研究并揭示两性离子SBMA水凝胶和PEG水凝胶之间的差异的人。总体而言，一系列体内系统测试表明，与PEG水凝胶相比，两性离子SBMA水凝胶在几乎所有方面均表现出优异的伤口愈合特性。