FIXATION IN TOTAL KNEE REPLACEMENT

无骨水泥全膝关节置换术（TKR）的关键问题包括假体在宿主骨骼上的固定的建立和维持。该建议涉及(i)使用局部递送的生长因子通过骨长入多孔涂层来增强早期固定，（ii）刺激骨再生的循环活性的初步表征，以及（iii）生长因子增强固定随时间推移的机械能力。虽然拟议的实验是在考虑到TKR的情况下设计的，但研究结果将与通过膜内骨形成发生骨愈合的任何情况相关。在即将到来的资助周期中，我们计划确定tgf - β和BMP-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会导致循环因子的释放，从而解释我们在偏远部位观察到的骨再生提高。量化使用这些生长因子后，非负重种植体的早期和长期固定强度的增加以及负重种植体的机械稳定性。提出的假设将使用两种体内犬模型和体外细胞和组织培养技术进行测试。现在美国每年进行的膝关节置换手术超过26.5万例，而1990年为12万例。不同制造商之间存在相当大的差异，据报道，近50%的胫骨假体设计用于无骨水泥植入，通过骨长入多孔表面，假体附着在宿主骨骼上。尽管近几年来无骨水泥TKR植入物的比例总体上有所下降，但这种类型的替代部件的绝对数量实际上可能在增加。假设骨长入界面的优点是，组织可以随着时间的推移而重塑，避免疲劳损伤的积累，而惰性界面（如骨水泥提供的界面）可能会发生疲劳损伤。我们的第一个假设检验了tgf - β和BMP-2之间的相互作用（协同作用或加性效应），以增强骨再生。第二个假设检验生长因子诱导的骨再生增强后是否存在循环活性。第三个假设与生长因子刺激骨的短期和中期机械能力有关，第四个假设解决了一个简单的问题：考虑到在承重植入物的界面上不可避免地存在间隙，这种抑制骨长入的状况是否可以通过使用已知的刺激骨愈合的生长因子来克服，骨骼再生的增强是否会导致植入物更大的稳定性？

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?