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生物功能细胞外基质-聚己内酯-羟基磷灰石支架与滑膜间充质干细胞/软骨细胞修复软骨缺损。

Biofunctional Extracellular Matrix-Polycaprolactone-Hydroxyapatite Scaffold and Synovium Mesenchymal Stem Cells/Chondrocytes for Repairing Cartilage Defects.

机构信息

Oncological Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital (the Affiliated Stomatological Hospital) of Xinjiang Medical University, Xinjiang Uygur Autonomous Region Institute of Stomatology, Urumqi, China.

出版信息

Tissue Eng Part A. 2021 Oct;27(19-20):1250-1263. doi: 10.1089/ten.TEA.2020.0245. Epub 2021 Feb 23.

Abstract

Articular cartilage defects and degeneration can be caused by multiple factors, and the current clinical treatment schemes for pathological changes are relatively limited. Engineered cartilage tissue represents an alternative therapy for repairing cartilage defects in regenerative medicine. The scaffold material is considered the framework of tissue engineering; thus, scaffold material selection plays a crucial role in the therapy outcome. Polycaprolactone (PCL)-hydroxyapatite (HA) has been applied as a scaffold material for bone and cartilage tissue engineering with nontoxic, harmless metabolites and proper physical properties. The extracellular matrix (ECM) is mainly composed of collagen and proteoglycan, as well as a large number of growth factors and cytokines, which provide a tissue-specific microenvironment for host cells. Adipose-derived stem cells are pluripotent stem cells, and transforming growth factor-β3 (TGF-β3) enables mesenchymal stem cells to promote ECM production. This study, via and experiments, elucidated that the synovium mesenchymal stem cells (SMSCs) + chondrocytes + ECM-PCL-HA repair system, which is constructed upon the ECM-PCL-HA scaffold material, exhibits an adequate chondrogenic ability and reparatory effect. Overall, ECM-PCL-HA can be defined as a biofunctional scaffold material. The SMSCs + chondrocytes + ECM-PCL-HA repair system showed good confluency between the new cartilage and the surface, as well as the interface of the adjacent host cartilage. Furthermore, the structure of new cartilage tissue is consistent with adjacency. Thus, it can be used as a preferred plan for articular cartilage defect repair. Impact statement Studies investigating the chondrogenic ability and reparatory effect of the synovium mesenchymal stem cells (SMSCs) + chondrocytes + extracellular matrix (ECM)-polycaprolactone (PCL)-hydroxyapatite (HA) repair system provided a theoretical and practical basis for choosing ECM-PCL-HA as the scaffold material for cartilage tissue engineering. In this study, the transforming growth factor-β3 (TGF-β3) gene was introduced into adipose-derived stem cells (ADSCs) using a lentiviral vector to enhance ECM production. The decellularized ADSCs-ECM-PCL-HA acted as a biofunctional scaffold material with suitable physicochemical properties, which was advantageous for SMSC and chondrocyte adhesion and growth. Lastly, the SMSCs + chondrocytes + ECM-PCL-HA repair system showed excellent capability in the flush fusion state of the prosthetic surface and interface.

摘要

关节软骨缺损和退变可由多种因素引起,目前针对病理性变化的临床治疗方案相对有限。工程化软骨组织代表了再生医学中修复软骨缺损的一种替代疗法。支架材料被认为是组织工程的框架,因此支架材料的选择对治疗效果至关重要。聚己内酯(PCL)-羟基磷灰石(HA)已被应用于骨和软骨组织工程的支架材料,具有无毒、无害的代谢物和适当的物理性能。细胞外基质(ECM)主要由胶原蛋白和蛋白聚糖以及大量生长因子和细胞因子组成,为宿主细胞提供组织特异性的微环境。脂肪来源的干细胞是多能干细胞,转化生长因子-β3(TGF-β3)使间充质干细胞能够促进 ECM 的产生。本研究通过 和 实验,阐明了构建在 ECM-PCL-HA 支架材料上的滑膜间充质干细胞(SMSCs)+软骨细胞+ECM-PCL-HA 修复系统具有足够的软骨生成能力和修复效果。总体而言,ECM-PCL-HA 可被定义为一种具有生物功能的支架材料。SMSCs+软骨细胞+ECM-PCL-HA 修复系统显示出新软骨与表面以及相邻宿主软骨之间良好的融合度。此外,新软骨组织的结构与毗邻处一致。因此,它可以作为关节软骨缺损修复的首选方案。 研究意义 研究滑膜间充质干细胞(SMSCs)+软骨细胞+细胞外基质(ECM)-聚己内酯(PCL)-羟基磷灰石(HA)修复系统的软骨生成能力和修复效果为选择 ECM-PCL-HA 作为软骨组织工程支架材料提供了理论和实践依据。在这项研究中,通过慢病毒载体将转化生长因子-β3(TGF-β3)基因导入脂肪来源的干细胞(ADSCs),以增强 ECM 的产生。脱细胞 ADSCs-ECM-PCL-HA 作为一种具有合适理化性能的生物功能支架材料,有利于 SMSC 和软骨细胞的黏附和生长。最后,SMSCs+软骨细胞+ECM-PCL-HA 修复系统在假体表面和界面的平齐融合状态下表现出优异的性能。

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