Calcium silicate-human serum albumin composite hydrogel decreases random pattern skin flap necrosis by attenuating vascular endothelial cell apoptosis and inflammation
Calcium silicate-human serum albumin composite hydrogel decreases random pattern skin flap necrosis by attenuating vascular endothelial cell apoptosis and inflammation
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硅酸钙-人血清白蛋白复合水凝胶通过减轻血管内皮细胞凋亡和炎症来减少随机型皮瓣坏死
DOI：
10.1016/j.cej.2021.130285
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发表时间：
2021-06-05
影响因子：
15.1
通讯作者：
Liu, Kai
中科院分区：
文献类型：
--
作者：
Xu, Peng;Xing, Min;Liu, Kai
随机模式皮瓣通常用于整形外科，以修复皮肤缺损。然而，由于皮瓣的存活主要依赖于远端蒂和创面床的血供，皮瓣的远端部分容易坏死。随后的病理反应，包括炎症反应、细胞凋亡和氧化应激，也加重皮瓣坏死。硅酸钙具有促进血管生成、减少细胞凋亡等多种生物活性，同时具有良好的生物相容性和安全性，因此受到人们的广泛关注。同时，人血清白蛋白（HSA）水凝胶具有优良的药物载体特性和良好的粘度，适合临床应用。在这里，CS掺入HSA水凝胶形成生物活性复合水凝胶，并控制其凝胶化时间。在第（-1）天将PBS、CS-PBS、HSA水凝胶和CS-HSA水凝胶注射到皮瓣下，并在第0天进行皮瓣手术。在第7天，CS-HSA水凝胶组的皮瓣坏死率随着血液灌注的增加而显著降低。术后7天，皮瓣下的CS-HSA水凝胶持续释放Si离子。组织学染色显示CD 31+血管显著增加，细胞凋亡减少，CD 68+巨噬细胞浸润。体外实验表明，低浓度的CS提取物可维持人脐静脉内皮细胞（HUVECs）的细胞活力、迁移和管形成能力。CS提取物也减少HUVEC凋亡在葡萄糖/氧剥夺条件下。在这些条件下，巨噬细胞炎症反应降低。基于这些结果，复合CS-HSA水凝胶适合于临床应用，并且可以通过减少血管内皮细胞凋亡和炎症来改善随机模式皮瓣的存活。
Random pattern skin flaps are commonly used in plastic surgery to repair skin defects. However, as flap survival mainly relies on blood supply from the distal pedicle and the wound bed, the distal part of the flap is prone to necrosis. Subsequent pathological reactions, including inflammatory reactions, cell apoptosis, and oxidative stress, also aggravate skin flap necrosis. Calcium silicate (CS) has gained attention for its multiple bioactive functions, including promoting angiogenesis and decreasing cell apoptosis, as well as its excellent biocompatibility and safety. Meanwhile, human serum albumin (HSA) hydrogel exhibits excellent drug carrier characteristics and good viscosity for clinical applications. Here, CS was incorporated into HSA hydrogel to form a bioactive composite hydrogel and to control its gelling time. PBS, CS-PBS, HSA hydrogel, and CS-HSA hydrogel were injected under skin flaps on day (-1) and skin flap surgery was performed on day 0. On day 7, the skin flap necrosis rate of the CS-HSA hydrogel group was significantly decreased with increased blood perfusion. Si ions were consistently released from the CS-HSA hydrogel under the skin flap 7 days after operation. Histological staining showed significantly increased CD31+ blood vessels, decreased cell apoptosis, and CD68+ macrophage infiltration. In vitro assays showed that low concentrations of CS extracts sustained cell viability, migration, and tube formation ability of human umbilical vein endothelial cells (HUVECs). CS extracts also decreased HUVEC apoptosis under glucose/oxygen-deprived conditions. Under these conditions, the macrophage inflammatory response decreased. Based on these results, composite CS-HSA hydrogel is suitable for clinical application, and can improve random pattern skin flap survival by attenuating vascular endothelial cell apoptosis and inflammation.