Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect
Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect
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DOI：
10.1002/term.2883
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发表时间：
2019-08-01
影响因子：
3.3
通讯作者：
Tuan, Rocky S.
中科院分区：
文献类型：
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作者：
Lin, Hang;Beck, Angela M.;Tuan, Rocky S.
目前还没有完全修复关节软骨损伤的治疗方法。我们实验室最近开发了一种可见光激活的甲基丙烯酸明胶(MGL)水凝胶，具有软骨再生的潜力。在这项研究中，我们通过补充甲基丙烯酸化透明质酸(MHA)进一步优化了MGL支架，MHA已被证明通过激活关键的细胞信号通路来刺激软骨生成。我们推测，引入最佳比例的MHA将增强MGL支架的生物学特性，并增强人骨髓间充质干细胞(HBMSCs)的软骨形成。为了验证这一假设，制备了由不同重量比的MGL和MHA组成的杂化支架，将hBMSCs包裹在20×10(6)cell/ml的浓度下，并将其保持在促进软骨形成的介质中。培养8周后，检测不同支架材料中的hBMSCs向软骨细胞分化的情况。我们的结果表明，当MGL/MHA的比例为9：1(%，w/v)时，hBMSC的肥大程度最低，糖胺聚糖的产量最高，整个结构的体积略有增加。然后在体内检测这种优化设计的MGL/MHA杂化支架在软骨修复中的适用性。手术造成兔股骨髁全层圆柱形骨软骨缺损区，并通过原位光交联法构建三维细胞-生物材料结构，以完全填充病变部位。结果表明，MGL/MHA(9：1)支架植入12周后，软骨和软骨下骨均得到再生，支持其作为临床修复和表面处理关节软骨缺损的良好支架材料。
There is no therapy currently available for fully repairing articular cartilage lesions. Our laboratory has recently developed a visible light-activatable methacrylated gelatin (mGL) hydrogel, with the potential for cartilage regeneration. In this study, we further optimized mGL scaffolds by supplementing methacrylated hyaluronic acid (mHA), which has been shown to stimulate chondrogenesis via activation of critical cellular signalling pathways. We hypothesized that the introduction of an optimal ratio of mHA would enhance the biological properties of mGL scaffolds and augment chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). To test this hypothesis, hybrid scaffolds consisting of mGL and mHA at different weight ratios were fabricated with hBMSCs encapsulated at 20 x 10(6) cells/ml and maintained in a chondrogenesis-promoting medium. The chondrogenenic differentiation of hBMSCs, within different scaffolds, was estimated after 8 weeks of culture. Our results showed that mGL/mHA at a 9:1 (%, w/v) ratio resulted in the lowest hBMSC hypertrophy and highest glycosaminoglycan production, with a slightly increased volume of the entire construct. The applicability of this optimally designed mGL/mHA hybrid scaffold for cartilage repair was then examined in vivo. A full-thickness cylindrical osteochondral defect was surgically created in the rabbit femoral condyle, and a three-dimensional cell-biomaterial construct was fabricated by in situ photocrosslinking to fully fill the lesion site. The results showed that implantation of the mGL/mHA (9:1) construct resulted in both cartilage and subchondral bone regeneration after 12 weeks, supporting its use as a promising scaffold for repair and resurfacing of articular cartilage defects, in the clinical setting.