title: Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery.
abstract: 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.
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Hee Seok
authors.initials: HS
authors.lastname: Yang
authors.forename: Wan-Geun
authors.initials: WG
authors.lastname: La
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Hak-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gun-Il
authors.initials: GI
authors.lastname: Im
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D054544:Arthroplasty, Subchondral; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005337:Fibrin / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D051457:Hyaline Cartilage / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D013314:Stress, Mechanical; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D006025:Glycosaminoglycans; D005337:Fibrin