miRNA induced 3D bioprinted-heterotypic osteochondral interface.
miRNA induced 3D bioprinted-heterotypic osteochondral interface.
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DOI：
10.1088/1758-5090/ac7fbb
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发表时间：
2022-08-17
期刊：
影响因子：
9
通讯作者：
Ozbolat, Ibrahim T.
中科院分区：
文献类型：
--
作者：
Celik, Nazmiye;Kim, Myoung Hwan;Yeo, Miji;Kamal, Fadia;Hayes, Daniel J.;Ozbolat, Ibrahim T.
骨软骨界面的工程化仍然是一个挑战。microRNA（miRs）已成为调节人类肌肉骨骼系统中成骨和软骨形成的分化和增殖的重要工具。在这里，我们描述了一种基于miR转染的脂肪源性干细胞（ADSC）球状体的三维（3D）生物打印的骨软骨重建新方法，以产生异型界面，该界面解决了传统方法通过使用可扩散细胞因子诱导区域分化的内在局限性。我们评估了miR-148 b的递送用于成骨分化以及miR-140和miR-21的共递送用于ADSC球体的软骨分化。我们的研究结果表明，miR转染的ADSC球状体表现出成骨和软骨分化相关的基因和蛋白质标记物的表达上调，并增强矿化和细胞增殖相比，使用市售分化培养基分化的球状体。在使用抽吸辅助生物打印确认miR转染的ADSC球状体的成骨和软骨形成潜力后，将这些球状体3D生物打印成双层异型骨软骨界面，其具有分层排列的不同成骨和软骨形成区。所提出的方法在分层组织的生物制造中具有很大的前景，不仅用于本工作中提出的骨软骨界面，而且用于其他复合组织和组织界面，例如但不限于骨-肌腱-肌肉界面和颅面组织。
Engineering of osteochondral interfaces remains a challenge. MicroRNAs (miRs) have emerged as significant tools to regulate the differentiation and proliferation of osteogenic and chondrogenic formation in the human musculoskeletal system. Here, we describe a novel approach to osteochondral reconstruction based on three-dimensional (3D) bioprinting of miR-transfected adipose-derived stem cell (ADSC) spheroids to produce a heterotypic interface that addresses the intrinsic limitations of the traditional approach in inducing zonal differentiation via the use of diffusible cytokines. We evaluated the delivery of miR-148b for osteogenic differentiation and the codelivery of miR-140 and miR-21 for chondrogenic differentiation of ADSC spheroids. Our results demonstrated that miR-transfected ADSC spheroids exhibited upregulated expression of osteogenic and chondrogenic differentiation related gene and protein markers, and enhanced mineralization and cell proliferation compared to spheroids differentiated using commercially-available differentiation medium. Upon confirmation of osteogenic and chondrogenic potential of miR-transfected ADSC spheroids, using aspiration-assisted bioprinting, these spheroids were 3D bioprinted into a dual-layer heterotypic osteochondral interface with stratified arrangement of distinct osteogenic and chondrogenic zones. The proposed approach holds great promise in biofabrication of stratified tissues, not only for osteochondral interfaces presented in this work, but also for other composite tissues and tissue interfaces, such as but not limited to bone-tendon-muscle interface and craniofacial tissues.
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