Nie Xiaolei, Chuah Yon Jin, Zhu Wenzhen, He Pengfei, Peck Yvonne, Wang Dong-An
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore; Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region.
Biomaterials. 2020 Mar;235:119821. doi: 10.1016/j.biomaterials.2020.119821. Epub 2020 Jan 26.
Articular cartilage repair has been a long-standing challenge in orthopaedic medicine due to the limited self-regenerative capability of cartilage tissue. Currently, cartilage lesions are often treated by microfracture or autologous chondrocyte implantation (ACI). However, these treatments are frequently reported to result in a mixture of the desired hyaline cartilage and mechanically inferior fibrocartilage. In this study, by combining the advantages of cartilage tissue engineering and decellularization technology, we developed a decellularized allogeneic hyaline cartilage graft, named dLhCG, which achieved superior efficacy in articular cartilage repair and surpassed living autologous chondrocyte-based cartilaginous engraftment and ACI. By the 6-month time point after implantation in porcine knee joints, the fine morphology, composition, phenotype, microstructure and mechanical properties of the regenerated hyaline-like cartilaginous neo-tissue have been demonstrated via histology, biochemical assays, DNA microarrays and mechanical tests. The articular cartilaginous engraftment with allogeneic dLhCG was indicated to be well consistent, compatible and integrated with the native cartilage of the host. The successful repair of articular chondral defects in large animal models suggests the readiness of allogeneic dLhCG for clinical trials.
由于软骨组织的自我再生能力有限,关节软骨修复一直是骨医学领域长期面临的挑战。目前,软骨损伤常通过微骨折或自体软骨细胞植入(ACI)进行治疗。然而,这些治疗方法经常被报道会导致所需的透明软骨和机械性能较差的纤维软骨混合形成。在本研究中,通过结合软骨组织工程和脱细胞技术的优势,我们开发了一种脱细胞异体透明软骨移植物,命名为dLhCG,其在关节软骨修复中取得了卓越的疗效,超过了基于活自体软骨细胞的软骨移植和ACI。在猪膝关节植入后的6个月时间点,通过组织学、生化分析、DNA微阵列和力学测试,已证实再生的类透明软骨新组织具有良好的形态、组成、表型、微观结构和力学性能。异体dLhCG的关节软骨移植被证明与宿主的天然软骨具有良好的一致性、相容性和整合性。在大型动物模型中成功修复关节软骨缺损表明异体dLhCG已具备进行临床试验的条件。