Osteochondral Repair Using a Scaffold-Free Tissue-Engineered Construct Derived from Synovial Mesenchymal Stem Cells and a Hydroxyapatite-Based Artificial Bone
Osteochondral Repair Using a Scaffold-Free Tissue-Engineered Construct Derived from Synovial Mesenchymal Stem Cells and a Hydroxyapatite-Based Artificial Bone
复制标题
DOI：
10.1089/ten.tea.2013.0414
复制
发表时间：
2014-09-01
影响因子：
4.1
通讯作者：
Nakamura, Norimasa
中科院分区：
文献类型：
--
作者：
Shimomura, Kazunori;Moriguchi, Yu;Nakamura, Norimasa
对于理想的骨软骨修复，重要的是促进软骨下骨和软骨的逐层分区恢复。具体而言，骨软骨连接的恢复和与邻近软骨的安全整合可能被认为是关键因素。本研究的目的是探讨一种由滑膜间充质干细胞（MSCs）衍生的无支架组织工程化结构（TEC）和羟基磷灰石（HA）人工骨组成的组合材料的可行性，使用兔骨软骨缺损模型。在成年兔股骨沟上造成骨软骨缺损。在使用前将TEC和HA人工骨杂交以形成组合植入物，然后将其植入缺损（N = 23）。在对照组中，仅植入HA（N = 18）。对修复组织进行组织学评价和微压痕试验。正常膝关节用作生物力学测试的额外对照组（N = 5）。在杂交时，TEC迅速附着在HA人工骨块的表面，该人工骨块可植入骨软骨缺损。在植入后6个月进行评估时，使用组合植入物治疗的骨软骨缺损显示出更快的软骨下骨修复，以及软骨组织的发育，与相邻宿主软骨的组织整合良好。相反，对照组表现出延迟的软骨下骨修复。此外，该组中的修复软骨组织与相邻软骨的整合较差，并含有成簇的软骨细胞，表明植入后6个月时出现早期骨关节炎（OA）样退行性变化。从生物力学角度来看，在6个月时用组合植入物治疗的骨软骨修复组织恢复了组织硬度，与正常骨软骨组织相似。组合植入物显著加速和改善骨软骨修复。具体而言，软骨下骨的早期修复以及修复软骨与邻近宿主组织的良好组织整合可能在加速骨软骨病损患者（包括OA患者）的术后康复和修复关节面的长期耐久性方面具有临床相关性。此外，考虑到TEC是一种无支架植入物，HA人工骨已被广泛应用于临床实践，因此在安全性和成本效益方面，组合植入物可被认为是一种有前途的基于MSC的生物植入物。
For an ideal osteochondral repair, it is important to facilitate zonal restoration of the subchondral bone and the cartilage, layer by layer. Specifically, restoration of the osteochondral junction and secure integration with adjacent cartilage could be considered key factors. The purpose of the present study was to investigate the feasibility of a combined material comprising a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) and a hydroxyapatite (HA) artificial bone using a rabbit osteochondral defect model. Osteochondral defects were created on the femoral groove of skeletally mature rabbits. The TEC and HA artificial bone were hybridized to develop a combined implant just before use, which was then implanted into defects (N = 23). In the control group, HA alone was implanted (N = 18). Histological evaluation and micro-indentation testing was performed for the evaluation of repair tissue. Normal knees were used as an additional control group for biomechanical testing (N = 5). At hybridization, the TEC rapidly attached onto the surface of HA artificial bone block, which was implantable to osteochondral defects. Osteochondral defects treated with the combined implants exhibited more rapid subchondral bone repair coupled with the development of cartilaginous tissue with good tissue integration to the adjacent host cartilage when assessed at 6 months post implantation. Conversely, the control group exhibited delayed subchondral bone repair. In addition, the repair cartilaginous tissue in this group had poor integration to adjacent cartilage and contained clustered chondrocytes, suggesting an early osteoarthritis (OA)-like degenerative change at 6 months post implantation. Biomechanically, the osteochondral repair tissue treated with the combined implants at 6 months restored tissue stiffness, similar to normal osteochondral tissue. The combined implants significantly accelerated and improved osteochondral repair. Specifically, earlier restoration of subchondral bone, as well as good tissue integration of repair cartilage to adjacent host tissue could be clinically relevant in terms of the acceleration of postoperative rehabilitation and longer-term durability of repaired articular surface in patients with osteochondral lesions, including those with OA. In addition, the combined implant could be considered a promising MSC-based bio-implant with regard to safety and cost-effectiveness, considering that the TEC is a scaffold-free implant and HA artificial bone has been widely used in clinical practice.