Kandel R A, Grynpas M, Pilliar R, Lee J, Wang J, Waldman S, Zalzal P, Hurtig M
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ont., Canada M5G 1X5.
Biomaterials. 2006 Aug;27(22):4120-31. doi: 10.1016/j.biomaterials.2006.03.005. Epub 2006 Mar 29.
There has been interest in developing novel biological treatments to repair focal cartilage defects. We have developed a method of forming biphasic constructs ("osteochondral"-type plug) in vitro consisting of cartilaginous tissue, formed on and anchored to the intended articulation surface of a porous ceramic substrate. The purpose of this study was to evaluate the biochemical and biomechanical properties and morphology of in vitro-formed biphasic constructs 3 and 9 months after implantation into 4mm diameter full thickness osteochondral defects in the trochlear groove of sheep stifles. The implants withstood loading in vivo up to 9 months with evidence of fusion to adjacent native cartilage and fixation by bone ingrowth into the ceramic substrate. The cartilage layer was eroded from those implants that were proud to the joint surface. Control implants (ceramic only) had fibrous tissue on the articulating surface after implantation for 3-4 months. Neither the cellularity nor proteoglycan content of the implanted cartilage, when it remained, changed significantly between 3 and 9 months and the collagen content increased slightly. The elastic equilibrium modulus of the cartilage improved with time with the greatest improvement (10-fold) occurring early during the first 3-4 months after implantation. This study suggests that biphasic constructs may be suitable to repair joint defects as the implants were maintained up to 9 months in sheep. Importantly the mechanical properties of the implanted cartilage improved significantly after implantation suggesting that cartilage can mature in vivo after implantation. The results indicate that further study of this treatment approach is warranted to attempt to overcome the technical surgical difficulties identified in this study.
人们一直对开发修复局灶性软骨缺损的新型生物疗法感兴趣。我们已经开发出一种在体外形成双相结构(“骨软骨”型栓体)的方法,该结构由软骨组织构成,形成于多孔陶瓷基质的预期关节表面并与之锚定。本研究的目的是评估将体外形成的双相结构植入绵羊膝关节滑车沟直径4mm的全层骨软骨缺损后3个月和9个月时的生化、生物力学特性及形态。植入物在体内承受负荷长达9个月,有证据表明其与相邻天然软骨融合,并通过骨长入陶瓷基质实现固定。突出于关节表面的植入物的软骨层被侵蚀。对照植入物(仅陶瓷)在植入3 - 4个月后,关节表面有纤维组织。植入的软骨在3至9个月期间,其细胞密度和蛋白聚糖含量(若仍存在)均无显著变化,胶原蛋白含量略有增加。软骨的弹性平衡模量随时间改善,在植入后的前3 - 4个月早期改善最为显著(提高了10倍)。本研究表明,双相结构可能适合修复关节缺损,因为植入物在绵羊体内可维持长达9个月。重要的是,植入后软骨的力学性能显著改善,表明软骨在植入后可在体内成熟。结果表明,有必要对这种治疗方法进行进一步研究,以试图克服本研究中发现的技术手术难题。