Biocompatibility Evaluation of Ionic- and Photo-Crosslinked Methacrylated Gellan Gum Hydrogels: In Vitro and In Vivo Study

Biocompatibility Evaluation of Ionic- and Photo-Crosslinked Methacrylated Gellan Gum Hydrogels: In Vitro and In Vivo Study
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DOI:
10.1002/adhm.201200256
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发表时间:
2013-04-01
影响因子:
10
通讯作者:
Reis, Rui L.
Reis, Rui L.
中科院分区:
工程技术1区
文献类型:
--
作者:
Silva-Correia, Joana;Zavan, Barbara;Reis, Rui L.

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在这项研究中,通过离子交联(iGG-MA)或光交联(phGG-MA)获得的甲基丙烯酸酯化结冷胶水凝胶的稳定性和生物相容性进行了体外和体内评价。甲基丙烯酸酯化结冷胶(GG-MA)粉末的尺寸排阻色谱分析显示,与未改性的材料相比,分子量较低,即,低酰基结冷胶。研究了iGG-MA和phGG-MA水凝胶在磷酸盐缓冲盐水溶液(pH 7.4)中的吸水和溶胀。首先通过制备细胞负载水凝胶来评价水凝胶的生物相容性。体外细胞包封研究表明,肺成纤维细胞(L929细胞)和人椎间盘(hIVD)细胞在两种水凝胶中培养时均可存活,培养时间长达21天。iGG-MA和phGG-MA水凝胶也皮下植入刘易斯大鼠10天和18天。通过组织学分析(苏木精-伊红染色)确定对水凝胶植入的组织反应。在植入的水凝胶周围观察到薄的纤维囊。未见坏死、钙化及急性炎症反应。本研究中呈现的结果表明,iGG-MA和phGG-MA水凝胶在体外和体内都是稳定的,支持L929和hIVD细胞的包封和活力,并且被发现在体内耐受性良好且无毒。
In this study, the stability and biocompatibility of methacrylated gellan gum hydrogels, obtained either by ionic- (iGG-MA) or photo-crosslinking (phGG-MA), were evaluated in vitro and in vivo. Size exclusion chromatography analysis of the methacrylated gellan gum (GG-MA) powder revealed that molecular weight is lower as compared to the non-modified material, i.e., low acyl gellan gum. The water uptake and swelling of iGG-MA and phGG-MA hydrogels were investigated in phosphate-buffered saline solution (pH 7.4). The biocompatibility of the hydrogels was firstly evaluated by producing cell-laden hydrogels. The in vitro cells encapsulation study showed that lung fibroblast cells (L929 cells) and human intervertebral disc (hIVD) cells are viable when cultured within both hydrogels, up to 21 days of culturing. The iGG-MA and phGG-MA hydrogels were also subcutaneously implanted in Lewis rats for 10 and 18 days. Tissue response to the hydrogels implantation was determined by histological analysis (haematoxylin-eosin staining). A thin fibrous capsule was observed around the implanted hydrogels. No necrosis, calcification, and acute inflammatory reaction were observed. The results presented in this study demonstrate that iGG-MA and phGG-MA hydrogels are stable in vitro and in vivo, support L929 and hIVD cells' encapsulation and viability, and were found to be well-tolerated and non-toxic in vivo.