Prostaglandin E2 hydrogel improves cutaneous wound healing via M2 macrophages polarization
Prostaglandin E2 hydrogel improves cutaneous wound healing via M2 macrophages polarization
复制标题
前列腺素 E-2 水凝胶通过 M2 巨噬细胞极化改善皮肤伤口愈合
DOI：
10.7150/thno.27385
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发表时间：
2018-01-01
期刊：
影响因子：
12.4
通讯作者：
Li, Zongjin
中科院分区：
文献类型：
--
作者：
Zhang, Shuaiqiang;Liu, Yuanyuan;Li, Zongjin
伤口愈合受一系列复杂的事件和重叠阶段的调控。在组织修复中，细胞因子和介质之间的微妙平衡是临床应用中最佳治疗所必需的。分子成像技术在监测活体细胞和分子事件方面具有多功能性，通过调节损伤部位细胞因子和介质的平衡，为更好地指导组织修复提供了有形的选择。方法：建立小鼠皮肤创伤愈合模型，研究将前列腺素E-2(PGE(2))掺入壳聚糖(CS)水凝胶(CS+PGE(2)水凝胶)是否可以提高其治疗效果。生物发光成像(BLI)用于无创性监测创面愈合过程中损伤部位的炎症和血管生成过程。结果：CS水凝胶可延长PGE(2)的释放，从而提高其组织修复和再生能力。分子成像结果显示，PGE(2)的长期释放可通过促进巨噬细胞M2表型转化而减轻炎症反应。此外，BLI显示，CS+PGE(2)水凝胶在组织修复的早期阶段可以促进损伤部位的血管生成。此外，CS+PGE(2)水凝胶在皮肤创面愈合过程中可以调节炎症、再生(血管生成)和重塑(纤维化)三个重叠阶段之间的平衡。结论：CS+PGE(2)水凝胶可作为一种新的治疗策略，通过M2巨噬细胞极化促进组织再生。此外，分子成像为实时监测组织修复过程中的细胞和分子事件提供了一个平台，并通过调节损伤部位细胞因子和介质的平衡来促进发现损伤修复的最佳治疗方法。
Wound healing is regulated by a complex series of events and overlapping phases. A delicate balance of cytokines and mediators in tissue repair is required for optimal therapy in clinical applications. Molecular imaging technologies, with their versatility in monitoring cellular and molecular events in living organisms, offer tangible options to better guide tissue repair by regulating the balance of cytokines and mediators at injured sites.Methods: A murine cutaneous wound healing model was developed to investigate if incorporation of prostaglandin E-2 (PGE(2)) into chitosan (CS) hydrogel (CS+PGE(2) hydrogel) could enhance its therapeutic effects. Bioluminescence imaging (BLI) was used to noninvasively monitor the inflammation and angiogenesis processes at injured sites during wound healing. We also investigated the Ml and M2 paradigm of macrophage activation during wound healing.Results: CS hydrogel could prolong the release of PGE(2), thereby improving its tissue repair and regeneration capabilities. Molecular imaging results showed that the prolonged release of PGE(2) could ameliorate inflammation by promoting the M2 phenotypic transformation of macrophages. Also, CS+PGE(2) hydrogel could augment angiogenesis at the injured sites during the early phase of tissue repair, as revealed by BLI. Furthermore, our results demonstrated that CS+PGE(2) hydrogel could regulate the balance among the three overlapping phases-inflammation, regeneration (angiogenesis), and remodeling (fibrosis)-during cutaneous wound healing.Conclusion: Our findings highlight the potential of the CS+PGE(2) hydrogel as a novel therapeutic strategy for promoting tissue regeneration via M2 macrophage polarization. Moreover, molecular imaging provides a platform for monitoring cellular and molecular events in real-time during tissue repair and facilitates the discovery of optimal therapeutics for injury repair by regulating the balance of cytokines and mediators at injured sites.