Vasospasm during reconstructive microsurgery is a common, uncertain, and devastating phenomena concerning flap survival. Topical vasodilators as antispasmodic agents are widely used to reduce vasospasm and enhance microvascular anastomosis in reconstructive microsurgery. In this study, thermo-responsive hydrogel (CNH) was fabricated by grafting chitosan (CS) and hyaluronic acid (HA) to poly(N-isopropylacrylamide) (PNIPAM). Papaverine, an anti-spasmodic agent, was then loaded to evaluate its effect on rat skin flap survival. Post-operative flap survival area and water content of rat dorsal skin flap were measured at 7 days after intradermal application of control hydrogel (CNHP0.0) and papaverine loaded hydrogel (CNHP0.4). Tissue malondialdehyde (MDA) content and superoxide dismutase (SOD) activity was measured using enzyme linked immunosorbent assay (ELISA) to determine oxidative stress in flaps. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) were performed to evaluate flap angiogenesis and inflammatory markers. Results showed that CNHP0.4 hydrogel could reduce tissue edema (35.63 ± 4.01%), improve flap survival area (76.30 ± 5.39%), increase SOD activity and decrease MDA content. Consequently, it also increased mean vessel density, upregulated expression of CD34 and VEGF, decreased macrophage infiltration, and reduced CD68 and CCR7 expression based on IHC staining. Overall, these results indicate that CNHP0.4 hydrogel can enhance angiogenesis with anti-oxidative and anti-inflammatory effects and promote skin flap survival by preventing vascular spasm.

Graphical Abstract

中文翻译：

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负载罂粟碱的可注射热敏水凝胶系统可提高大鼠背部皮瓣的存活率

重建显微外科手术期间的血管痉挛是一种关于皮瓣存活的常见、不确定且具有破坏性的现象。局部血管扩张剂作为解痉剂广泛用于重建显微外科手术中减少血管痉挛和增强微血管吻合。在这项研究中，通过将壳聚糖（CS）和透明质酸（HA）接枝到聚（N-异丙基丙烯酰胺）（PNIPAM）上制备了热响应水凝胶（CNH）。然后加载罂粟碱（一种抗痉挛剂）以评估其对大鼠皮瓣存活的影响。皮内应用对照水凝胶（CNHP0.0）和罂粟碱水凝胶（CNHP0.4）后7天测量大鼠背侧皮瓣的术后皮瓣存活面积和含水量。使用酶联免疫吸附测定（ELISA）测量组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性，以确定皮瓣的氧化应激。进行苏木精和伊红 (H&E) 染色和免疫组织化学 (IHC) 以评估皮瓣血管生成和炎症标志物。结果显示，CNHP0.4水凝胶可减轻组织水肿（35.63±4.01%），提高皮瓣成活面积（76.30±5.39%），增加SOD活性，降低MDA含量。因此，根据 IHC 染色，它还增加了平均血管密度，上调了 CD34 和 VEGF 的表达，减少了巨噬细胞浸润，并减少了 CD68 和 CCR7 的表达。总的来说，这些结果表明 CNHP0.

图形概要