1 Beijing Key Laboratory of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Institute of Orthopedics , Chinese PLA General Hospital, Beijing, People's Republic of China .
2 People's Hospital , Hulunbeier City, Hulunbeier, Neimenggu Province, People's Republic of China .
Tissue Eng Part A. 2018 Jun;24(11-12):905-914. doi: 10.1089/ten.TEA.2017.0223. Epub 2018 Feb 2.
Previously, we synthesized an articular cartilage extracellular matrix (ECM)-derived oriented scaffold for cartilage tissue engineering, which was biomimetic in terms of structure and biochemical composition. However, the limit resource of the cartilage-derived ECM is a hindrance for its application. In this study, we developed a new material for cartilage tissue engineering-human umbilical cord Wharton's jelly-derived ECM (hWJECM). The hWJECM has an abundant resource and similar biochemistry with cartilage ECM, and the use of it is not associated with ethical controversy. We adopted the method previously used in cartilage ECM-derived oriented scaffold preparation to generate the oriented hWJECM-derived scaffold, and the scaffold properties were tested in vitro and in vivo. The three-dimensional scaffold has a porous and well-oriented structure, with a mean pore diameter of ∼104 μm. Scanning electron microscopy and cell viability staining results demonstrated that the oriented scaffold has good biocompatibility and cell alignment. In addition, we used functional autologous chondrocytes to seed the hWJECM-derived oriented scaffold and tested the efficacy of the cell-scaffold constructs to repair the full-thickness articular cartilage defect in a rabbit model. Defects of 4 mm diameter were generated in the patellar grooves of the femurs of both knees and were implanted with chondrocyte-scaffold constructs (group A) or scaffolds alone (group B); rabbits with untreated defects were used as a control (group C). Six months after surgery, all defects in group A were filled completely with repaired tissue, and most of which were hyaline cartilage. In contrast, the defects in group B were filled partially with repaired tissue, and approximately half of these repaired tissues were hyaline cartilage. The defects in group C were only filled with fibrotic tissue. Histological grading score of group A was lower than those of groups B and C. Quantification of glycosaminoglycan indicated that newly formed cartilage in group A rabbits was comparable with normal cartilage. In conclusion, hWJECM-derived oriented scaffolds loaded with autologous chondrocytes induced cartilage repair in rabbit knees, which was comparable with native cartilage in terms of macroscopic view, microstructure, and biochemical composition.
先前,我们合成了一种关节软骨细胞外基质(ECM)衍生的定向支架,用于软骨组织工程,该支架在结构和生化组成方面具有仿生特性。然而,软骨衍生 ECM 的有限资源是其应用的障碍。在这项研究中,我们为软骨组织工程开发了一种新材料——人脐带华通氏胶 ECM(hWJECM)。hWJECM 资源丰富,其生化特性与软骨 ECM 相似,使用它不会引起伦理争议。我们采用了先前用于软骨 ECM 衍生定向支架制备的方法来制备定向 hWJECM 衍生支架,并在体外和体内测试了支架性能。三维支架具有多孔且定向良好的结构,平均孔径约为 104μm。扫描电子显微镜和细胞活力染色结果表明,定向支架具有良好的生物相容性和细胞排列。此外,我们使用功能自体软骨细胞接种 hWJECM 衍生的定向支架,并在兔模型中测试了细胞-支架构建物修复全层关节软骨缺损的功效。在双膝髌沟中生成 4mm 直径的缺损,并将软骨细胞-支架构建物(A 组)或单独的支架(B 组)植入;未处理缺陷的兔子作为对照组(C 组)。手术后 6 个月,A 组的所有缺损均完全被修复组织填充,其中大部分为透明软骨。相比之下,B 组的缺损仅部分被修复组织填充,其中约一半的修复组织为透明软骨。C 组的缺损仅被纤维组织填充。A 组的组织学分级评分低于 B 组和 C 组。糖胺聚糖的定量分析表明,A 组兔子的新形成软骨与正常软骨相当。总之,负载自体软骨细胞的 hWJECM 衍生定向支架可诱导兔膝关节软骨修复,在宏观外观、微观结构和生化组成方面与天然软骨相当。