FIXATION IN TOTAL KNEE REPLACEMENT

无骨水泥全膝关节置换术(TKR)的关键问题包括建立和维持假体对宿主骨骼的固定。这项建议涉及(I)使用局部输送的生长因子通过骨生长到多孔涂层中来加强早期固定，(Ii)刺激骨再生的循环活动的初步特征，以及(Iii)随着时间的推移生长因子增强的固定的机械能力。尽管这些拟议的实验是在考虑TKR的情况下设计的，但这些发现将与任何通过膜内骨形成发生骨愈合的情况相关。在即将到来的赠款周期中，我们计划确定转化生长因子-β和骨形态发生蛋白-2是相加还是协同作用，以确定局部生长因子诱导的骨再生刺激是否导致循环因子的释放，以解释我们观察到的偏远部位骨再生的升高，以量化使用这些生长因子时非负重植入物的早期和长期固定强度的增加以及负重植入物的机械稳定性。提出的假说将通过两种活体犬模型以及体外细胞和组织培养技术进行验证。目前，美国每年进行的膝关节置换手术超过265,000例，而1990年为120,000例。不同的制造商有相当大的差异，一些制造商报告说，近50%的胫骨部件是为非骨水泥植入而设计的，通过骨生长进入多孔表面，部件与宿主骨骼相连。尽管在过去的几年里，非骨水泥TKR植入物的比例总体上有了相对的下降，但这种类型的替换部件的绝对数量实际上可能会增加。骨生长界面的假设优势是，组织可以随着时间的推移进行重塑，并避免疲劳损伤的积累，而惰性界面可能会发生这种情况，例如骨水泥提供的界面。我们的第一个假设检验了促进骨再生的转化生长因子-β和骨形态发生蛋白-2之间的相互作用(协同作用与相加效应)。第二个假设检验在生长因子诱导的骨再生增强后是否存在循环活动。第三种假说与生长因子刺激的骨的短期和中期机械能力有关，第四种假说解决了一个简单的问题：鉴于负重种植体界面不可避免地存在间隙，这种抑制骨生长的情况能否通过使用已知的刺激骨愈合的生长因子来克服，以及骨再生的增强是否会带来更大的种植体稳定性？

Key issues in cementless total knee replacement (TKR) include the establishment and maintenance of fixation of the components to the host skeleton. This proposal is concerned with (i) using locally delivered growth factors to enhance early fixation by bone ingrowth into a porous coating, (ii) initial characterization of a circulating activity that stimulates bone regeneration and (iii) the mechanical competence of growth factor- enhanced fixation over time. Although the proposed experiments are designed with TKR in mind the findings will be relevant to any situation in which bone healing occurs through intramembranous bone formation. In the upcoming grant cycle, we plan to determine if TGF-beta and BMP-2 act additively or synergistically, to determine if local growth factor- induced stimulation of bone regeneration leads to the release of circulating factors that could explain our observations of elevated bone regeneration at remote sites, to quantify the increase in the early and long-term strength of fixation of non weight bearing implants and the mechanical stability of weight bearing implants when these growth factors are used. The proposed hypotheses will be tested using two in vivo canine models and in vitro cell and tissue culture techniques. More than 265,000 knee replacement procedures are now performed annually in the U.S compared to a rate of 120,000 annually in 1990. There is considerable variation among manufacturers with some reporting nearly 50% of the tibial components being designed for cementless implantation, whereby the component becomes attached to the host skeleton by bone ingrowth into a porous surface. Although there has been a relative decrease in the proportion of cementless TKR implants overall in the last few years, the absolute numbers of this type of replacement component may actually be increasing. The hypothetical advantage of a bone ingrowth interface is that the tissue can remodel over time and avoid accumulation of fatigue damage as can occur with inert interfaces such as those provided by bone cement. Our first hypothesis examines interaction (synergy v. additive effects) between TGF-beta and BMP-2 for enhancement of bone regeneration. The second hypothesis tests if a circulating activity is present after growth factor-induced augmentation of bone regeneration. The third hypothesis is concerned with the short and intermediate-term mechanical competence of growth factor stimulated bone and the fourth hypothesis address a simple question: given that gaps are inevitably present at the interface in weight- bearing implants, can this bone ingrowth-inhibiting condition be overcome with the use of growth factors known to stimulate bone healing and does enhancement of bone regeneration lead to greater implant stability?