Focal chondral and osteochondral defects create significant pain and disability for working-aged adults. Current osteochondral repair grafts are limited in availability and often fail due to insufficient osseous support and integration. Thus, a need exists for an off-the-shelf osteochondral construct with the propensity to overcome these shortcomings. Herein, a scalable process was used to develop a multi-layered osteochondral graft with a subchondral bone (ScB) phase tailored to support bone healing and integration. Multiple ScB formulations and fabrication techniques were screened via degradation, bioactivity, and unconfined compression testing. An optimized ScB construct was selected and its cytotoxicity assessed. Additionally, a cartilage analog was secured to the optimized ScB construct via a calcified cartilage layer, and the resulting osteochondral construct was characterized via interfacial shear and dynamic mechanical testing. The optimized ScB construct did not significantly alter local pH during degradation, exhibited measurable bioactivity in vitro, and had significantly greater compressive mechanical strength compared to other constructs. The attachment strength of the cartilage analog was significantly greater by an increase in compressive dynamic mechanical properties. Furthermore, this ScB construct was found to be cytocompatible with human bone marrow-derived mesenchymal stromal cells. Taken together, this optimized ScB material forms the robust foundation of a novel, off-the-shelf osteochondral construct to be used in defect repair.

Statement of Significance

The quality of life for millions of individuals worldwide is detrimentally affected by focal chondral or osteochondral defects. Current off-the-shelf biomaterial constructs often fail to repair these defects due to insufficient osseous support and integration. Herein, we used a scalable process to fabricate and optimize a novel boney construct. This optimized boney construct demonstrated biochemical, physical, and mechanical properties tailored to promote bone healing. Furthermore, a novel cartilage analog was successfully attached to the boney construct, forming a multi-layered osteochondral construct.

中文翻译：

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定制多层骨软骨构造的软骨下骨相以支持骨愈合和软骨类似物

局灶性软骨和骨软骨缺损为工作年龄的成年人带来了明显的疼痛和残疾。当前的骨软骨修复移植物的可用性有限，并且常常由于骨支持和整合不足而失败。因此，需要一种具有克服这些缺点的现成的骨软骨构造。在本文中，可扩展的过程被用来开发具有软骨下骨（ScB）相的多层骨软骨移植物，其被定制以支持骨愈合和整合。通过降解，生物活性和无限制压缩测试筛选了多种ScB配方和制造技术。选择优化的ScB构建体并评估其细胞毒性。此外，通过钙化软骨层将软骨类似物固定在优化的ScB构建体上，并通过界面剪切和动态力学测试对得到的骨软骨构造进行了表征。优化的ScB构建体在降解过程中不会显着改变局部pH值，表现出可测量的生物活性与其他构建体相比，在体外具有更高的压缩机械强度。通过增加压缩动态力学性能，软骨类似物的附着强度显着提高。此外，发现该ScB构建体与人骨髓来源的间充质基质细胞具有细胞相容性。综上所述，这种优化的ScB材料构成了一种新型的现成的骨软骨构造物的坚固基础，该构造物可用于缺陷修复。

重要声明

局灶性软骨或骨软骨缺损严重影响了全球数百万个人的生活质量。由于骨支撑和整合不足，当前的现成生物材料构造常常无法修复这些缺陷。在本文中，我们使用了可扩展的过程来制造和优化新型的骨骼结构。这种经过优化的多骨构造证明了为促进骨骼愈合而专门设计的生化，物理和机械性能。此外，新型软骨类似物成功地连接到骨结构上，形成多层骨软骨结构。