An ex vivo model using human osteoarthritic cartilage demonstrates the release of bioactive insulin-like growth factor-1 from a collagen-glycosaminoglycan scaffold.
An ex vivo model using human osteoarthritic cartilage demonstrates the release of bioactive insulin-like growth factor-1 from a collagen-glycosaminoglycan scaffold.
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DOI：
10.1002/cbf.3112
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发表时间：
2015-07
影响因子：
3.6
通讯作者：
Rushton N
中科院分区：
文献类型：
--
作者：
Wardale J;Mullen L;Howard D;Ghose S;Rushton N
仿生支架对于软骨的治疗性修复具有很大的希望，但是尽管大多数支架在体外用细胞进行测试，但是很少有体外模型（EVM），其中成人软骨和支架在体内研究之前共培养以优化它们的相互作用。本研究描述了一种简单的，非压缩的方法，适用于哺乳动物或人类软骨，并提供了一个合理的样品吞吐量。全深度关节软骨切片的环来源于经历骨关节炎的膝关节置换的人供体，并且插入胶原/糖胺聚糖仿生支架（Tigenix，UK）的3 mm核心以产生EVM。将成人骨关节炎软骨细胞接种到支架中，并将培养物维持长达30天。离体模型在整个实验中是稳定的，并且细胞保持存活。接种到EVM中的软骨细胞附着在整个支架上并与软骨外植体接触。细胞迁移和细胞外基质蛋白在支架中的沉积被生长因子增强，特别是如果支架预先装载有生长因子。这项研究表明，EVM代表了一种合适的模型，在进行昂贵的临床前试验之前，它有可能测试一系列治疗参数，如细胞数量/类型、生长因子或治疗药物。© 2015作者。用于软骨修复的生物材料的临床前试验非常昂贵，并且通常研究直接从使用分离细胞的体外研究进展到体内研究，而不调查靶组织和支架之间的相互作用。我们的研究使用来自患有骨关节炎的成年人供体的活软骨，因此代表了支架设计的确切场景。该系统价格便宜且设置简单，适合48孔板格式，这意味着可以获得合理的通量。这将该模型用于治疗药物测试。
Biomimetic scaffolds hold great promise for therapeutic repair of cartilage, but although most scaffolds are tested with cells in vitro, there are very few ex vivo models (EVMs) where adult cartilage and scaffolds are co-cultured to optimize their interaction prior to in vivo studies. This study describes a simple, non-compressive method that is applicable to mammalian or human cartilage and provides a reasonable throughput of samples. Rings of full-depth articular cartilage slices were derived from human donors undergoing knee replacement for osteoarthritis and a 3 mm core of a collagen/glycosaminoglycan biomimetic scaffold (Tigenix, UK) inserted to create the EVM. Adult osteoarthritis chondrocytes were seeded into the scaffold and cultures maintained for up to 30 days. Ex vivo models were stable throughout experiments, and cells remained viable. Chondrocytes seeded into the EVM attached throughout the scaffold and in contact with the cartilage explants. Cell migration and deposition of extracellular matrix proteins in the scaffold was enhanced by growth factors particularly if the scaffold was preloaded with growth factors. This study demonstrates that the EVM represents a suitable model that has potential for testing a range of therapeutic parameters such as numbers/types of cell, growth factors or therapeutic drugs before progressing to costly pre-clinical trials. © 2015 The Authors. Cell Biochemistry and Function Published by John Wiley & Sons Ltd. Pre-clinical trials of biomaterials for cartilage repair are very costly, and all too often, studies progress directly from in vitro studies using isolated cells to in vivo studies without investigating the interaction between the target tissue and the scaffold. Our study uses viable cartilage from adult human donors with osteoarthritis and therefore represents the exact scenario that the scaffold is designed for. The system is cheap and simple to set up and is suitable for a 48-well plate format, meaning a reasonable throughput is obtainable. This lends the model to therapeutic drug testing.