Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite

被引:312
作者
Sharma, Blanka [1 ,2 ]
Fermanian, Sara
Gibson, Matthew [1 ,2 ]
Unterman, Shimon [1 ,2 ]
Herzka, Daniel A. [1 ,2 ]
Cascio, Brett [3 ]
Coburn, Jeannine [1 ,2 ,4 ]
Hui, Alexander Y. [1 ,2 ]
Marcus, Norman
Gold, Garry E. [5 ]
Elisseeff, Jennifer H. [1 ,2 ,4 ]
机构
[1] Johns Hopkins Univ, Wilmer Eye Inst, Translat Tissue Engn Ctr, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA
[3] Lake Charles Mem Hosp, Dept Orthoped, Lake Charles, LA 70601 USA
[4] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
[5] Stanford Univ, Dept Radiol Bioengn & Orthopaed Surg, Stanford, CA 94305 USA
关键词
MESENCHYMAL STEM-CELLS; AUTOLOGOUS CHONDROCYTE IMPLANTATION; MICROFRACTURE TECHNIQUE; CHONDROITIN SULFATE; RANDOMIZED-TRIAL; FOLLOW-UP; KNEE; DEFECTS; DIFFERENTIATION; BONE;
D O I
10.1126/scitranslmed.3004838
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
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页数:9
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