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定制多层骨软骨构建体的软骨下骨相以支持骨愈合和软骨类似物。

Tailoring the subchondral bone phase of a multi-layered osteochondral construct to support bone healing and a cartilage analog.

机构信息

The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson, SC, USA.

The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson, SC, USA.

出版信息

Acta Biomater. 2018 Sep 15;78:351-364. doi: 10.1016/j.actbio.2018.08.009. Epub 2018 Aug 10.

DOI:10.1016/j.actbio.2018.08.009
PMID:30099201
Abstract

UNLABELLED

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.

摘要

未加标签

局灶性软骨和软骨下骨缺损会给处于工作年龄段的成年人带来严重的疼痛和残疾。目前的软骨下骨修复移植物在供应上受到限制,并且由于缺乏足够的骨支持和整合,常常失败。因此,需要有一种现成的软骨下骨构建体,具有克服这些缺点的倾向。在此,使用可扩展的工艺来开发具有亚软骨(ScB)相的多层软骨下骨移植物,该相经过定制以支持骨愈合和整合。通过降解、生物活性和无约束压缩测试筛选了多种 ScB 配方和制造技术。选择了优化的 ScB 构建体并评估其细胞毒性。此外,通过钙化软骨层将软骨模拟物固定在优化的 ScB 构建体上,并通过界面剪切和动态力学测试对所得的软骨下骨构建体进行了表征。优化的 ScB 构建体在降解过程中不会显著改变局部 pH 值,在体外表现出可测量的生物活性,并且与其他构建体相比具有显著更高的压缩机械强度。软骨模拟物的附着强度通过压缩动态力学性能的增加而显著增加。此外,发现这种 ScB 构建体与人骨髓间充质基质细胞相容。总之,这种优化的 ScB 材料为新型现成软骨下骨构建体提供了坚固的基础,可用于缺陷修复。

意义声明

全世界数百万人的生活质量受到局灶性软骨或软骨下骨缺损的不利影响。目前的现成生物材料构建体由于缺乏足够的骨支持和整合,往往无法修复这些缺陷。在此,我们使用可扩展的工艺来制造和优化新型骨构建体。这种优化的骨构建体表现出经过定制以促进骨愈合的生化、物理和机械性能。此外,成功地将新型软骨模拟物附着到骨构建体上,形成了多层软骨下骨构建体。

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