Aspiration-assisted bioprinting of the osteochondral interface

Aspiration-assisted bioprinting of the osteochondral interface
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DOI:
10.1038/s41598-020-69960-6
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发表时间:
2020-08-04
期刊:
影响因子:
4.6
通讯作者:
Ozbolat, Ibrahim T.
Ozbolat, Ibrahim T.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ayan, Bugra;Wu, Yang;Ozbolat, Ibrahim T.

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骨软骨缺损包括关节软骨和软骨下骨的损伤,这是骨科手术的一个重大挑战。在骨软骨(OC)界面生物制造的情况下,必须考虑骨、软骨和骨-软骨界面的分层结构。本研究采用新开发的吸气辅助生物打印技术(AAB)对双层OC界面进行生物打印,这是无支架生物打印首次应用于OC界面工程。利用人脂肪源性干细胞(ADSCs)形成的组织球体,在三维空间(3D)上分化为软骨性和成骨性的组织球体,并通过免疫染色、组织学、生物化学和基因表达进行定性鉴定。值得注意的是,OC界面是通过将一层成骨球体精确定位在牺牲的海藻酸盐支架上,然后在同一支架上覆盖另一层软骨球体来实现生物打印的。单个区域的球体融合以及两个区域表型的维持证实了与组织形态学相关的OC界面的成功生物构建。不使用聚合物支架的OC组织模型的生物构建不仅在再生医学方面,而且在骨关节炎的药物测试和疾病建模方面显示出巨大的潜力。
Osteochondral defects contain damage to both the articular cartilage and underlying subchon- dral bone, which remains a significant challenge in orthopedic surgery. Layered structure of bone, cartilage and the bone-cartilage interface must be taken into account in the case of biofabrication of the osteochondral (OC) interface. In this study, a dual layered OC interface was bioprinted using a newly developed aspiration-assisted bioprinting (AAB) technique, which has been the first time that scaffold-free bioprinting was applied to OC interface engineering. Tissue spheroids, made of human adipose-derived stem cells (ADSCs), were differentiated in three dimensions (3D) into chondrogenic and osteogenic spheroids, which were confirmed by immunostaining and histology qualitatively, and biochemistry assays and gene expression, quantitatively. Remarkably, the OC interface was bioprinted by accurate positioning of a layer of osteogenic spheroids onto a sacrificial alginate support followed by another layer of chondrogenic spheroids overlaid by the same support. Spheroids in individual zones fused and the maintenance of phenotypes in both zones confirmed the successful biofabrication of the histomorphologically-relevant OC interface. The biofabrication of OC tissue model without the use of polymeric scaffolds unveils great potential not only in regenerative medicine but also in drug testing and disease modeling for osteoarthritis.