Bioinspired nanofibers support chondrogenesis for articular cartilage repair
Bioinspired nanofibers support chondrogenesis for articular cartilage repair
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DOI：
10.1073/pnas.1121605109
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发表时间：
2012-06-19
影响因子：
11.1
通讯作者：
Elisseeff, Jennifer H.
中科院分区：
文献类型：
--
作者：
Coburn, Jeannine M.;Gibson, Matthew;Elisseeff, Jennifer H.
随着人口老龄化，关节软骨修复仍然是一个重要且不断增长的临床挑战。关节软骨的天然细胞外基质（ECM）是由蛋白质纤维和水凝胶基质组成的3D结构，其一起提供物理和生物学线索以指导细胞行为。在这里，我们提出了纤维支架组成的聚乙烯醇和生物线索硫酸软骨素的纤维尺寸在纳米级的应用于关节软骨修复。所描述的生物相容性支架的独特的低密度性质允许立即的细胞浸润以实现最佳的组织修复。在体外评估支架促进软骨样组织形成的能力。与颗粒培养物相比，所述支架增强了间充质干细胞的成软骨分化，如通过增加的ECM产生和软骨特异性基因表达所指示的，同时还允许细胞增殖。当植入大鼠骨软骨缺损时，脱细胞骨支架支持增强软骨形成，其特征在于蛋白聚糖的产生在空的缺损中最小。此外，列入硫酸软骨素纤维增强软骨特异性II型胶原合成在体外和体内。通过模拟天然ECM的物理和生物学线索，骨基质支架增强了软骨组织形成，表明其对关节软骨修复的潜在效用。
Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair.