Hyaline Cartilage Regeneration by Combined Therapy of Microfracture and Long-Term Bone Morphogenetic Protein-2 Delivery

• Published in: Tissue engineering. Part A 2011-07, Vol.17 (13-14), p.189-1818
• Main Authors: Yang, Hee Seok, La, Wan-Geun, Bhang, Suk Ho, Kim, Hak-Jun, Im, Gun-Il, Lee, Haeshin, Park, Jung-Ho, Kim, Byung-Soo
• Format: Article
• Language: English
• Subjects: Animals; Arthroplasty, Subchondral; Blotting, Western; Bone Morphogenetic Protein 2 - administration & dosage; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic proteins; Cartilage; Cartilage, Articular - drug effects; Cartilage, Articular - pathology; Collagen; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Fibrin - pharmacology; Fractures; Glycosaminoglycans - metabolism; Humans; Hyaline Cartilage - drug effects; Kinetics; Mice; Original Articles; Physical therapy; Physiological aspects; Proteins; Rabbits; Regeneration - drug effects; Stress, Mechanical; Time Factors; Wound Healing - drug effects
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2010.0540

Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. Here, we tested the hypothesis that long-term delivery of BMP-2 to cartilage defects subjected to microfracture results in regeneration of high-quality hyaline-like cartilage, as opposed to short-term delivery of BMP-2 or no BMP-2 delivery. Heparin-conjugated fibrin (HCF) and normal fibrin were used as carriers for the long- and short-term delivery of BMP-2, respectively. Rabbit articular cartilage defects were treated with microfracture combined with one of the following: no treatment, fibrin, short-term delivery of BMP-2, HCF, or long-term delivery of BMP-2. Eight weeks after treatment, histological analysis revealed that the long-term delivery of BMP-2 group (microfracture + HCF + BMP-2) showed the most staining with alcian blue. A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.