Gullbrand Sarah E, Kim Dong Hwa, Ashinsky Beth G, Bonnevie Edward D, Smith Harvey E, Mauck Robert L
Translational Musculoskeletal Research Center Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USA.
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery University of Pennsylvania Philadelphia Pennsylvania USA.
JOR Spine. 2020 May 13;3(2):e1086. doi: 10.1002/jsp2.1086. eCollection 2020 Jun.
Tissue-engineered whole disc replacements are an emerging treatment strategy for advanced intervertebral disc degeneration. A challenge facing the translation of tissue-engineered disc replacement to clinical use are the opposing needs of initial immobilization to advantage integration contrasted with physiologic loading and its anabolic effects. Here, we utilize our established rat tail model of tissue engineered disc replacement with external fixation to study the effects of remobilization at two time points postimplantation on engineered disc structure, composition, and function. Our results suggest that the restoration of mechanical loading following immobilization enhanced collagen and proteoglycan content within the nucleus pulposus and annulus fibrosus of the engineered discs, in addition to improving the integration of the endplate region of the construct with native bone. Despite these benefits, angulation of the vertebral bodies at the implanted level occurred following remobilization at both early and late time points, reducing tensile failure properties in the remobilized groups compared to the fixed group. These results demonstrate the necessity of restoring physiologic mechanical loading to engineered disc implants in vivo, and the need to transition toward their evaluation in larger animal models with more human-like anatomy and motion compared to the rat tail.
组织工程化全椎间盘置换是一种针对晚期椎间盘退变的新兴治疗策略。将组织工程化椎间盘置换转化为临床应用面临的一个挑战是，既要进行初始固定以利于整合，又要考虑生理负荷及其合成代谢作用，这两种需求相互矛盾。在此，我们利用已建立的大鼠尾巴组织工程化椎间盘置换并进行外固定的模型，研究植入后两个时间点重新活动对工程化椎间盘结构、组成和功能的影响。我们的结果表明固定后恢复机械负荷可增加工程化椎间盘髓核和纤维环内的胶原蛋白和蛋白聚糖含量，此外还可改善植入物终板区域与天然骨的整合。尽管有这些益处，但在早期和晚期时间点重新活动后，植入水平的椎体均出现了成角现象，与固定组相比，重新活动组的拉伸破坏特性降低。这些结果证明了在体内恢复工程化椎间盘植入物生理机械负荷的必要性，以及需要转向在与大鼠尾巴相比具有更类似人体解剖结构和运动的大型动物模型中对其进行评估。
