Department of Orthopaedic Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jyonan-ku, Fukuoka 814-0180, Japan.
J Biomed Mater Res B Appl Biomater. 2010 Jul;94(1):80-8. doi: 10.1002/jbm.b.31627.
Our previous studies showed that a mechano-active scaffold made of poly(L-lactide-co-epsilon-caprolactone) (PLCL) exhibited a high potential to realize the formation of a functional, engineered cartilage in vitro. This animal study therefore was designed to investigate the feasibility of repairing on osteochondral defect with the use of bone marrow-derived mesenchymal stem cells (BMSCs) incorporated with a PLCL scaffold. Rabbit BMSCs, isolated and subsequently cultured in monolayer, were seeded into a porous PLCL scaffold sponge following an implantation onto a full-thickness osteochondral defect (diameter of 4.5 mm, depth of 5 mm) that was artificially created on the medial femoral condyles at a high load-bearing site on a rabbit's knee joint. Time-dependent healing of the defect was evaluated by macroscopic, histological examinations at both 3- and 6-month-implantations, respectively. A PLCL sponge incorporated with BMSCs exhibited sufficient structural support, resulting in new osteochondral tissue regeneration: a physiologically well-integrated subchondral bone formation, a hyaline cartilage-like morphology containing chondrocytes surrounded by abundant cartilaginous matrices. In addition, quantitative biochemical assays also demonstrated high potential for the synthesis of sulfated glycosaminoglycan and collagen, both of which are biomolecules essential to extracelluar matrix in normal cartilage tissue. In contrast, defects filled with cell-free PLCL scaffold or left empty showed a very limited potential for regeneration. Our findings suggest that a composite of PLCL-based sponge scaffold and BMSCs promote the repair of osteochondral defects at high load-bearing sites in adult rabbits.
我们之前的研究表明,由聚(L-丙交酯-共-ε-己内酯)(PLCL)制成的机械活性支架具有很大的潜力,可以在体外实现功能性工程软骨的形成。因此,这项动物研究旨在探讨使用骨髓间充质干细胞(BMSCs)与 PLCL 支架结合修复高负荷兔膝关节股骨内侧髁全层骨软骨缺损的可行性。从兔骨髓中分离出的 BMSCs 经单层培养后,接种到多孔 PLCL 支架海绵中,然后将其植入到一个直径为 4.5mm、深度为 5mm 的全层骨软骨缺损处。该缺损是在兔膝关节高负荷部位的股骨内侧髁上人工创建的。通过分别在 3 个月和 6 个月的植入物时进行宏观和组织学检查,评估缺损的时间依赖性愈合情况。结果显示,与细胞游离的 PLCL 支架或空支架相比,含有 BMSCs 的 PLCL 海绵支架具有足够的结构支撑力,可促进新的骨软骨组织再生:形成了生理性良好整合的软骨下骨,具有软骨细胞围绕丰富软骨基质的透明软骨样形态。此外,定量生化分析也表明了合成硫酸化糖胺聚糖和胶原蛋白的巨大潜力,这两种生物分子都是正常软骨组织细胞外基质所必需的。我们的研究结果表明,PLCL 基海绵支架和 BMSCs 的复合物可促进成年兔高负荷部位骨软骨缺损的修复。