There is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D-bioplotted osteochondral scaffold design that can drive site-specific tissue formation when seeded with adipose-derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and compared to both open lesions and autologous explants. ICRS II evaluation indicated that defects with ASC-seeded scaffolds had healing that most closely resembled the aulogous explant. Scaffold-facilitated subchondral bone repair mimicked the structure of native bone tissue, but cartilage matrix staining was not apparent within the scaffold. The open lesions had the highest volumetric infill detected using CT analysis (p < 0.05), but the repair tissue was largely disorganized. The acellular scaffold without a tidemark had significantly more volumetric filling than either the acellular or ASC seeded groups containing a tidemark (p < 0.05), suggesting that the tidemark limited cell infiltration into the cartilage portion of the scaffold. Overall, scaffold groups repaired the defect more successfully than an open lesion but achieved limited repair in the cartilage region. With further optimization, this approach holds potential to treat focal cartilage lesions in a highly personalized manner using a human patient's own ASC cells.

中文翻译：

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评价接种脂肪干细胞的多相 3D 生物绘图支架修复猪模型中的骨软骨缺损

需要开发针对局灶性关节软骨损伤的有效治疗方法。我们之前开发了一种多相 3D 生物绘图骨软骨支架设计，当接种脂肪干细胞 (ASC) 时，该设计可以驱动特定部位的组织形成。本研究的目的是在大型动物模型中评估这种支架。在尤卡坦小型猪的滑车槽中产生骨软骨缺损，并使用含有或缺乏电纺潮标的支架进行修复，这些支架要么未播种，要么播种有 ASC。在 4 个月的体内植入过程中，通过计算机断层扫描 (CT) 监测植入物，并与开放性病变和自体外植体进行比较。ICRS II 评估表明，带有 ASC 种子支架的缺陷具有与自体外植体最相似的愈合。支架促进的软骨下骨修复模拟了天然骨组织的结构，但在支架内软骨基质染色不明显。使用 CT 分析检测到开放性病变的体积填充量最高（p  < 0.05），但修复组织在很大程度上杂乱无章。没有潮标的无细胞支架比含有潮标的无细胞或 ASC 接种组具有显着更多的体积填充 ( p  < 0.05)，这表明潮标限制了细胞浸润到支架的软骨部分。总体而言，支架组比开放性病变更成功地修复了缺损，但在软骨区域实现了有限的修复。通过进一步优化，这种方法有可能使用人类患者自己的 ASC 细胞以高度个性化的方式治疗局灶性软骨病变。