FIXATION IN TOTAL KNEE REPLACEMENT

这项建议旨在加强和保持对Tall的固定 膝关节置换(TKR)通过一种称为 骨长入。1992年，199,000例初次全膝关节置换术 在美国演出的，据估计，47%是 “无骨水泥”是一种依靠骨骼固定的植入物。 深入渗透的表面。 两种已知的通过骨内长抑制初始固定的条件，缺乏 种植体与支撑骨之间的均匀接触和在支撑骨 骨-种植体界面，不可避免地在一定程度上存在于 无水泥TKR。最近，我们发现：(一)转型增长 已知的骨修复刺激因子-β/1(转化生长因子-β/1)增强 非负重模型中的骨向内生长和(Ii)该骨 形态发生蛋白-2(BMP-2)在以下条件下保持其成骨诱导特性 应用于多孔涂层植入物。转化生长因子-β增强正在进行的过程 例如当在新鲜制造时本地输送时编织的骨形成 骨骼损伤的部位，而BMP通过诱导骨形成来发挥作用 通过一种软骨前体。因此，转化生长因子-β很可能会 在有坚固的固定但有间隙的情况下工作良好 界面。然而，转化生长因子-β促进骨生长的能力 运动的存在可能会有问题。BMP似乎很可能会 在界面存在时是促进骨向内生长的更好手段 运动由于其不同的作用机制。 因此，这两个假设旨在确定是否治疗 植入转化生长因子-β/1或骨形态发生蛋白-2可促进骨生长和 存在界面间隙和界面运动的种植体固定 无骨水泥TKR犬模型的建立。具体地说，剂量反应曲线 对于用每种生长因子处理的植入物将被确定，随后 通过测试来评估这些增长因素的增强潜力，使用 种植体固定稳定性和骨长入的定量测量 终端。这些研究将有助于确定在哪些情况下 将生长因子应用于种植体将有助于建立 对骨骼的固定。

This proposal is directed at enhancing and maintaining fixation of total knee replacement (TKR) implants to the skeleton through a process known as bone ingrowth. In 1992, 199,000 primary total knee replacements were performed in the U.S. Of these, it has been estimated that 47% are "cementless," a type of implant in which fixation depends upon bone ingrowth into a porous surface. Two conditions known to inhibit initial fixation by bone ingrowth, lack of uniform contact between the implant and supporting bone and motion at the bone-implant interface, are inevitably present to some degree in cementless TKR. Recently, we have found (i) that transforming growth factor-beta/1 (TGF-beta/1), a known stimulator of bone repair, enhances bone ingrowth in a non-weight-bearing model and (ii) that bone morphogenetic protein-2 (BMP-2) retains its osteoinductive properties when applied to a porous-coated implant. TGF-beta enhances ongoing processes such as woven bone formation when delivered locally at freshly created sites of skeletal injury, whereas BMP works by inducing bone to form through a cartilaginous precursor. Thus, it is likely that TGF-beta will work well in situations where there is rigid fixation but gaps at the interface. However, the ability of TGF-beta to promote bone ingrowth in the presence of motion may be problematic. It seems likely that BMP would be a better means of promoting bone ingrowth in the presence of interface motion because of its different mechanism of action. Thus, the two hypotheses are directed at determining if treatment of the implant with either TGF-beta/1 or BMP-2 can enhance bone ingrowth and implant fixation in the presence of interface gaps and interface motion in a canine model of cementless TKR. Specifically, the dose-response curve for implants treated with each growth factor will be determined, followed by tests to assess the enhancing potential of these growth factors, using quantitative measures of implant fixation stability and bone ingrowth as the endpoints. The studies will help to determine in which situations application of growth factors to implants will be helpful for establishing fixation to the skeleton.