Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Sci Transl Med. 2013 Jan 9;5(167):167ra6. doi: 10.1126/scitranslmed.3004838.
Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T(2)) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.
通过生物材料的进步和应用,软骨表面重建的手术选择可能会得到显著改善,这些生物材料可以指导组织修复。聚乙二醇二丙烯酸酯 (PEGDA) 水凝胶被设计用来支持软骨基质的产生,并且易于手术应用。体外模型系统证明了软骨特异性细胞外基质在水凝胶生物材料中的沉积,并刺激间充质干细胞相邻软骨组织的发育。为了将其转化为关节环境,在软骨和骨组织的关节缺损处应用硫酸软骨素黏合剂,使水凝胶与软骨和骨组织共价结合和黏附。在山羊模型的临床前测试后,启动了一项初步的临床研究,将生物材料系统与标准微骨折手术相结合,用于治疗 15 例内侧股骨髁局灶性软骨缺损的患者。对照组患者仅接受微骨折治疗。磁共振成像显示,与对照组相比,接受治疗的患者的组织填充水平显著更高。磁共振自旋-自旋弛豫时间 (T(2)) 显示,随着时间的推移,水含量减少,组织结构增加。与对照组相比,接受治疗的患者疼痛减轻,而膝关节功能 [国际膝关节文献委员会 (IKDC)] 评分在 6 个月的评估期内两组之间均有所增加。研究期间未观察到重大不良事件。随着进一步的临床测试,这种实用的生物材料策略有可能改善关节软骨缺损的治疗。