title: Osteochondral repair using a scaffold-free tissue-engineered construct derived from synovial mesenchymal stem cells and a hydroxyapatite-based artificial bone.
abstract: For an ideal osteochondral repair, it is important to facilitate zonal restoration of the subchondral bone and the cartilage, layer by layer. Specifically, restoration of the osteochondral junction and secure integration with adjacent cartilage could be considered key factors. The purpose of the present study was to investigate the feasibility of a combined material comprising a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) and a hydroxyapatite (HA) artificial bone using a rabbit osteochondral defect model. Osteochondral defects were created on the femoral groove of skeletally mature rabbits. The TEC and HA artificial bone were hybridized to develop a combined implant just before use, which was then implanted into defects (N=23). In the control group, HA alone was implanted (N=18). Histological evaluation and micro-indentation testing was performed for the evaluation of repair tissue. Normal knees were used as an additional control group for biomechanical testing (N=5). At hybridization, the TEC rapidly attached onto the surface of HA artificial bone block, which was implantable to osteochondral defects. Osteochondral defects treated with the combined implants exhibited more rapid subchondral bone repair coupled with the development of cartilaginous tissue with good tissue integration to the adjacent host cartilage when assessed at 6 months post implantation. Conversely, the control group exhibited delayed subchondral bone repair. In addition, the repair cartilaginous tissue in this group had poor integration to adjacent cartilage and contained clustered chondrocytes, suggesting an early osteoarthritis (OA)-like degenerative change at 6 months post implantation. Biomechanically, the osteochondral repair tissue treated with the combined implants at 6 months restored tissue stiffness, similar to normal osteochondral tissue. The combined implants significantly accelerated and improved osteochondral repair. Specifically, earlier restoration of subchondral bone, as well as good tissue integration of repair cartilage to adjacent host tissue could be clinically relevant in terms of the acceleration of postoperative rehabilitation and longer-term durability of repaired articular surface in patients with osteochondral lesions, including those with OA. In addition, the combined implant could be considered a promising MSC-based bio-implant with regard to safety and cost-effectiveness, considering that the TEC is a scaffold-free implant and HA artificial bone has been widely used in clinical practice.
authors.affiliation: 1 Department of Orthopaedics, Osaka University Graduate School of Medicine , Suita, Osaka, Japan .
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shimomura
authors.forename: Yu
authors.initials: Y
authors.lastname: Moriguchi
authors.forename: Wataru
authors.initials: W
authors.lastname: Ando
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Nansai
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujie
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: Alberto
authors.initials: A
authors.lastname: Gobbi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kita
authors.forename: Shuji
authors.initials: S
authors.lastname: Horibe
authors.forename: Konsei
authors.initials: K
authors.lastname: Shino
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Norimasa
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000138:chemical synthesis*; D002478:Cells, Cultured; D017886:Durapatite / Q000737:chemistry*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D005260:Female; D005264:Femoral Fractures / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation* / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology; D019736:Prostheses and Implants; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology*; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D018786:Bone Substitutes; D017886:Durapatite