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光交联、可注射丝胶蛋白水凝胶作为 3D 仿生细胞外基质,用于微创修复软骨。

Photo-crosslinkable, injectable sericin hydrogel as 3D biomimetic extracellular matrix for minimally invasive repairing cartilage.

机构信息

Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Respiration, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

Biomaterials. 2018 May;163:89-104. doi: 10.1016/j.biomaterials.2018.02.016. Epub 2018 Feb 9.

Abstract

Millions of patients worldwide suffer from cartilage injury and age/disease-related cartilage degeneration. However, cartilage, such as articular cartilage, is poor at self-regeneration. Current treatments are often invasive with limited efficacy. Developing minimal invasive strategies for effective cartilage repair is highly desired. Here, we report an injectable, photo-crosslinkable sericin hydrogel as a biomimetic extracellular matrix for minimal invasively repairing cartilage. Sericin was functionalized to be sericin methacryloyl (SerMA), which formed an in situ hydrogel upon UV light irradiation via photo-crosslinking. Possessing excellent biocompatibility, SerMA hydrogels were adhesive to chondrocytes, and promoted the proliferation of attached chondrocytes even in a nutrition-lacking condition. SerMA hydrogels exhibited photoluminescent property allowing real-time monitoring hydrogels' status. The mechanical properties and degradation rates (73% for SMH-1, 47% for SMH-2 and 37% for SMH-3 after 45 days) of SerMA hydrogels were readily tunable by varying methacryloyl modification degrees to meet various repair requirements. Notably, the in vivo implantation of chondrocyte-laden SerMA hydrogels effectively formed artificial cartilages after 8 weeks. Most importantly, the artificial cartilages molecularly resembled native cartilage as evidenced by high accumulation of cartilage-specific ECM components and upregulated expression of cartilage-critical genes. Together, this sericin hydrogel is a promising tissue engineering scaffold for generating artificial cartilage in vivo towards effective, minimal invasive cartilage repair.

摘要

全世界有数百万患者患有软骨损伤和与年龄/疾病相关的软骨退化。然而,软骨(如关节软骨)自我再生能力差。目前的治疗方法往往具有侵入性,疗效有限。因此,人们非常希望开发微创策略来有效修复软骨。在这里,我们报告了一种可注射的、光交联丝胶水凝胶,作为一种仿生细胞外基质,可微创修复软骨。丝胶被功能化为丝胶甲基丙烯酰(SerMA),通过紫外光照射可以通过光交联原位形成水凝胶。SerMA 水凝胶具有极好的生物相容性,与软骨细胞黏附,并促进附着的软骨细胞增殖,即使在营养缺乏的情况下也是如此。SerMA 水凝胶具有光致发光特性,允许实时监测水凝胶的状态。SerMA 水凝胶的机械性能和降解率(45 天后 SMH-1 为 73%,SMH-2 为 47%,SMH-3 为 37%)可以通过改变甲基丙烯酰化修饰程度来轻松调节,以满足各种修复要求。值得注意的是,负载软骨细胞的 SerMA 水凝胶的体内植入在 8 周后有效地形成了人工软骨。最重要的是,人工软骨在分子上类似于天然软骨,这表现为软骨特异性细胞外基质成分的大量积累和软骨关键基因的上调表达。总之,这种丝胶水凝胶是一种很有前途的组织工程支架,可用于在体内生成人工软骨,从而实现有效的微创软骨修复。

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