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利用 iPSC 来源的人软骨细胞的生物 3D 打印技术进行关节软骨再生。

Bio-3D printing iPSC-derived human chondrocytes for articular cartilage regeneration.

机构信息

Center for Regenerative Medicine Research, Faculty of Medicine, Saga University, Saga, Japan.

Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.

出版信息

Biofabrication. 2021 Aug 25;13(4). doi: 10.1088/1758-5090/ac1c99.

Abstract

Osteoarthritis is a leading cause of pain and joint immobility, the incidence of which is increasing worldwide. Currently, total joint replacement is the only treatment for end-stage disease. Scaffold-based tissue engineering is a promising alternative approach for joint repair but is subject to limitations such as poor cytocompatibility and degradation-associated toxicity. To overcome these limitations, a completely scaffold-free Kenzan method for bio-3D printing was used to fabricate cartilage constructs feasible for repairing large chondral defects. Human induced pluripotent stem cell (iPSC)-derived neural crest cells with high potential to undergo chondrogenesis through mesenchymal stem cell differentiation were used to fabricate the cartilage. Unified, self-sufficient, and functional cartilaginous constructs up to 6 cmin size were assembled by optimizing fabrication time during chondrogenic induction. Maturation for 3 weeks facilitated the self-organisation of the cells, which improved the construct's mechanical strength (compressive and tensile properties) and induced changes in glycosaminoglycan and type II collagen expression, resulting in improved tissue function. The compressive modulus of the construct reached the native cartilage range of 0.88 MPa in the 5th week of maturation. This paper reports the fabrication of anatomically sized and shaped cartilage constructs, achieved by combining novel iPSCs and bio-3D printers using a Kenzan needle array technology, which may facilitate chondral resurfacing of articular cartilage defects.

摘要

骨关节炎是导致疼痛和关节活动受限的主要原因,其发病率在全球范围内呈上升趋势。目前,全关节置换是治疗终末期疾病的唯一方法。基于支架的组织工程学是一种很有前途的关节修复替代方法,但存在细胞相容性差和降解相关毒性等局限性。为了克服这些局限性,采用了一种完全无支架的 Kenzen 生物 3D 打印方法来制造可行的软骨构建体,用于修复大的软骨缺损。使用具有高软骨分化潜力的人诱导多能干细胞(iPSC)衍生的神经嵴细胞通过间充质干细胞分化来制造软骨。通过优化软骨形成过程中的制造时间,组装出统一的、自给自足的、功能齐全的软骨构建体,其大小可达 6cm。成熟 3 周后,促进了细胞的自组织,提高了构建体的机械强度(压缩和拉伸性能),并诱导了糖胺聚糖和 II 型胶原蛋白表达的变化,从而改善了组织功能。构建体的压缩模量在第 5 周成熟时达到了 0.88MPa 的天然软骨范围。本文报告了使用 Kenzen 针阵列技术结合新型 iPSC 和生物 3D 打印机制造解剖学大小和形状的软骨构建体的方法,这可能有助于关节软骨缺损的软骨表面修复。

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