Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes.
Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes.
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DOI：
10.1016/j.jconrel.2016.07.043
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发表时间：
2016-09
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影响因子：
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通讯作者：
Yunxiao Zhu;Ryan A. Hoshi;Siyu Chen;Ji Yi;C. Duan;R. Galiano;Hao F. Zhang;G. Ameer
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文献类型：
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作者：
Yunxiao Zhu;Ryan A. Hoshi;Siyu Chen;Ji Yi;C. Duan;R. Galiano;Hao F. Zhang;G. Ameer
糖尿病足溃疡（DFU）是糖尿病的严重并发症。由于微循环缺陷以及活性氧产生过多和延长而导致的细胞迁移改变与 DFU 的延迟愈合有关。本研究的目的是评估基于柠檬酸盐的抗氧化剂热敏聚合物持续释放 SDF-1（一种促进内皮祖细胞归巢和血管生成的趋化因子）是否会显着改善糖尿病受损的真皮伤口愈合。通过连续缩聚和自由基聚合反应合成了聚(聚乙二醇柠檬酸酯-共-N-异丙基丙烯酰胺)(PPCN)。在高于其最低临界溶液温度 (LCST) 的 PPCN + SDF-1 溶液中捕获 SDF-1，并测量其释放和生物活性。使用大体观察、组织学、免疫组织化学和光学相干断层扫描微血管造影，在糖尿病小鼠夹板切除真皮伤口模型中评估了从 PPCN (PPCN + SDF-1) 中持续释放 SDF-1 与快速注射磷酸盐缓冲盐水 (PBS) 中的 SDF-1 对伤口愈合的影响。增加 PPCN 浓度会降低 SDF-1 的释放速率。对于用 PPCN + SDF-1、仅 SDF-1、仅 PPCN 和 PBS 治疗的伤口，达到 50% 伤口闭合的时间分别为 11 天、16 天、14 天和 17 天。用 PPCN + SDF-1 治疗的伤口完全愈合的时间最短（24 天），并表现出加速的肉芽组织生成、上皮成熟和最高的灌注血管密度。总之，从 PPCN 中持续释放 SDF-1 是一种有前途且易于使用的治疗策略，可改善慢性不愈合 DFU 的治疗。
Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus. Altered cell migration due to microcirculatory deficiencies as well as excessive and prolonged reactive oxygen species production are implicated in the delayed healing of DFUs. The goal of this research was to assess whether sustained release of SDF-1, a chemokine that promotes endothelial progenitor cell homing and angiogenesis, from a citrate-based antioxidant thermoresponsive polymer would significantly improve impaired dermal wound healing in diabetes. Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) was synthesizedviasequential polycondensation and free radical polymerization reactions. SDF-1 was entrappedviagelation of the PPCN + SDF-1 solution above its lower critical solution temperature (LCST) and its release and bioactivity was measured. The effect of sustained release of SDF-1 from PPCN (PPCN + SDF-1)versusa bolus application of SDF-1 in phosphate buffered saline (PBS) on wound healing was evaluated in a diabetic murine splinted excisional dermal wound model using gross observation, histology, immunohistochemistry, and optical coherence tomography microangiography. Increasing PPCN concentration decreased SDF-1 release rate. The time to 50% wound closure was 11 days, 16 days, 14 days, and 17 days for wounds treated with PPCN + SDF-1, SDF-1 only, PPCN only, and PBS, respectively. Wounds treated with PPCN + SDF-1 had the shortest time for complete healing (24 days) and exhibited accelerated granulation tissue production, epithelial maturation, and the highest density of perfused blood vessels. In conclusion, sustained release of SDF-1 from PPCN is a promising and easy to use therapeutic strategy to improve the treatment of chronic non-healing DFUs.