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Hybrid extracellular matrix design for cartilage-mediated bone regeneration

机译:软骨介导的骨再生杂交细胞外基质设计

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Recapitulating long bone repair through endochondral ossification (EO) is increasingly becoming a more popular approach. A successful EO Process depends greatly on the establishment of a healthy hypertrophic-cartilage template (HCT). The aim of this work is to design a hydrogel system, which closely mimics the extracellular matrix of HCT. We examined the combinatorial effect of two commonly used hydrogels for bone and cartilage regeneration strategies, hyaluronan (HA) and fibrin (FB), to induce HCT formation. Hydrogel combinations were evaluated using a clinically relevant cell source, human bone marrow mesenchymal stem cells (hBMSCs). The results establish that with increasing HA (50-90%) the chondrogenic and its subsequent hypertrophy trend improved, with 70:30 HA:FB combination showing the highest and most uniform expression of chondrogenic and hypertrophic stage specific markers. This combination also showed superior support for cell micro-aggregation and differentiation. Thus, 70:30 HA-FB matrix demonstrated a healthy formation of chondrogenic and hypertrophic stages with rich stage-specific ECM components. This study demonstrates that with the appropriate hydrogel design it is possible to develop effective tissue engineering therapies for bone defect repair and regeneration through endochondral ossification by establishing a healthy HCT. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 300-309, 2018.
机译:通过CondoChondral骨化(EO)重新承载长骨骼修复越来越多地成为一种更受欢迎的方法。成功的EO过程取决于建立健康的肥大 - 软骨模板(HCT)。这项工作的目的是设计水凝胶系统,它密切模仿HCT的细胞外基质。我们检查了两种常用水凝胶的组合效果,用于骨和软骨再生策略,透明质酸(HA)和纤维蛋白(FB),以诱导HCT形成。使用临床相关的细胞来源,人骨髓间充质干细胞(HBMSCs)评估水凝胶组合。结果表明,随着HA(50-90%)的软骨生成及其随后的肥大趋势改善,70:30 HA:FB组合显示有软骨菌和肥厚阶段特异性标记的最高和最均匀的表达。这种组合还显示出对细胞微聚集和分化的优异支持。因此,70:30的HA-FB基质证明了具有丰富的阶段特异性ECM组分的软骨形成和肥厚阶段的健康形成。本研究表明,通过适当的水凝胶设计,通过建立健康的HCT,可以通过内心骨化进行骨缺损修复和再生的有效组织工程疗法。 (c)2017年Wiley期刊,Inc。J生物保解率A件B:苹果生物摩特,106B:300-309,2018。

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