Department of Orthopaedic Surgery, National University of Singapore, Singapore.
Critical Analytics for Manufacturing Personalised-Medicine, Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore.
Cartilage. 2022 Apr-Jun;13(2):19476035221093063. doi: 10.1177/19476035221093063.
The zonal properties of articular cartilage critically contribute to the mechanical support and lubrication of the tissue. Current treatments for articular cartilage have yet to regenerate this zonal architecture, thus compromising the functional efficacy of the repaired tissue and leading to tissue degeneration in the long term. In this study, the efficacy of zonal cartilage regeneration through bilayered implantation of expanded autologous zonal chondrocytes was investigated in a porcine chondral defect model.
Autologous chondrocytes extracted from articular cartilage in the non-weight bearing trochlea region of the knee were subjected to an expansion-sorting strategy, integrating dynamic microcarrier (dMC) culture, and spiral microchannel size-based zonal chondrocyte separation. Zonal chondrocytes were then implanted as bilayered fibrin hydrogel construct in a porcine knee chondral defect model. Repair efficacy was compared with implantation with cell-free fibrin hydrogel and full thickness (FT) cartilage-derived heterogenous chondrocytes. Cartilage repair was evaluated 6 months after implantation.
Sufficient numbers of zonal chondrocytes for implantation were generated from the non-weight bearing cartilage. Six-month repair outcomes showed that bilayered implantation of dMC-expanded zonal chondrocytes resulted in substantial recapitulation of zonal architecture, including chondrocyte arrangement, specific Proteoglycan 4 distribution, and collagen alignment, that was accompanied by healthier underlying subchondral bone.
These results demonstrate that with appropriate expansion and isolation of zonal chondrocytes, the strategy of stratified zonal chondrocyte implantation represents a significant advancement to Autologous Chondrocyte Implantation-based cartilage regeneration, with the potential to improve the long-term integrity of the regenerated tissues.
关节软骨的分区特性对组织的力学支撑和润滑至关重要。目前的关节软骨治疗方法尚未能再生这种分区结构，从而影响修复组织的功能效果，并导致组织在长期内退化。在这项研究中，通过双层植入扩增的自体分区软骨细胞，研究了在猪软骨缺损模型中再生分区软骨的效果。
从膝关节非负重滑车区域的关节软骨中提取的自体软骨细胞采用了一种扩增-分选策略，整合了动态微载体（dMC）培养和螺旋微通道大小的分区软骨细胞分离。然后将分区软骨细胞作为双层纤维蛋白水凝胶构建体植入猪膝关节软骨缺损模型中。将修复效果与无细胞纤维蛋白水凝胶和全厚（FT）软骨源性异质软骨细胞的植入进行比较。植入后 6 个月评估软骨修复情况。
从非负重软骨中产生了足够数量的可用于植入的分区软骨细胞。6 个月的修复结果表明，dMC 扩增的分区软骨细胞双层植入导致分区结构的大量重现，包括软骨细胞排列、特定的蛋白聚糖 4 分布和胶原排列，同时伴随着更健康的下方软骨下骨。
这些结果表明，通过适当的分区软骨细胞扩增和分离，分层分区软骨细胞植入策略代表了基于自体软骨细胞植入的软骨再生的重大进展，有可能提高再生组织的长期完整性。
