Failure Mechanisms of Joint Replacement

关节置换的失效机制

• 批准号: 6875327
• 负责人: Joan E Bechtold
• 金额: $ 22.95万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6875327
• 关键词: arthrodesis; biological models; biomaterial compatibility; biomaterial evaluation; biomaterial interface interaction; bone transplantation; computed axial tomography; dogs; enzyme linked immunosorbent assay; growth factor; hydroxyapatites; implant; joint prosthesis; longitudinal animal study; mechanical stress; medical implant science; medical rehabilitation related tag; orthopedics; radiography; titanium

DESCRIPTION (provided by applicant): Our long-term goal is to improve the clinical success of revision joint replacements. In our original application, we developed an experimental model of the revision implant setting. The model uses our established weight-loaded micromotion device, to engender a revision cavity with a tissue morphology representing an aseptically loosened human implant. At revision surgery, the pistoning PMMA implant is replaced with a prescribed implant/graft treatment. In our earlier work, we identified diminished osteogenic performance as a major deficit of revision implants, and we identified the relatively impermeable sclerotic bone (SB) rim that forms during the process of aseptic loosening as a major factor in this poorer fixation. We focus on this devitalized sclerotic bone rim since fixation in the sclerotic region is known to be critical clinically for achieving overall stability of a revision implant. We have successfully shown that cracking (perforating) the sclerotic bone rim improved revision fixation 5-7 fold. Addition of bone graft increased fixation up to 40 fold, and, with rim cracking, hydroxyapatite (HA) implants had superior fixation to their titanium (Ti) counterparts. Graft improved fixation in all settings investigated. We will study hypotheses addressing three Aims, based on promising results from the prior funding period. Aim 1: to provide greater access (of native growth factors, cells, marrow) to the revision interface by perforating (cracking) the sclerotic bone rim. We will compare rim cracking to the procedure of reaming to remove the SB rim. Aim 2: to improve utilization of native growth factors and cells by coatings encouraging bone growth directly on the revision implant surface. Aim 3: to augment the revision interface with local application of bone graft and bone graft substitutes, with and without bone marrow aspirate and platelet rich plasma (PRP) concentrates. For Aim 1, the two access techniques studied are rim cracking and reaming. For Aim 2, the three revision implant coatings studied are Ti, HA + RGD and Poly, D, Lactide (PLDDA) (with TGFb1 and IGF1). For Aim 3, the four augmentations studied are allograft, coralline hydroxyapatite, with and without marrow aspirate and PRP. Sixteen paired groups of these treatments will determine effectiveness, interactions and synergies of treatments. Outcome measures are histomorphometric (% bone area and implant contact in zones, and connectivity) micro-CT (including bone volume, surface to volume ratio, anisotropy index), and mechanical (static pushout strength, stiffness, energy, and dynamic damping factor and damping odulus). Our active partnership of an accomplished clinician scientist and his team, and bioengineers and scientists bring a diverse set of competencies working towards our common goal. Our good collaborations and established and clinically verified experimental model is a strong base for future studies to improve the longevity of clinically vexing revision implants.

描述（由申请人提供）：我们的长期目标是提高翻修关节置换术的临床成功率。在我们最初的申请中，我们开发了一个翻修植入物设置的实验模型。该模型使用我们建立的重量加载微动装置，以产生一个翻修腔，其组织形态代表无菌松动的人类植入物。在翻修手术中，将活塞式PMMA植入物替换为规定的植入物/移植物治疗。在我们早期的工作中，我们确定成骨性能下降是翻修植入物的主要缺陷，并且我们确定在无菌性松动过程中形成的相对不可渗透的坐骨（SB）边缘是这种较差固定的主要因素。我们关注这种失活的坐骨边缘，因为众所周知，坐骨区域的固定在临床上对于实现翻修植入物的整体稳定性至关重要。我们已经成功地证明，硬化骨边缘破裂（穿孔）可以将翻修固定提高5-7倍。添加骨移植物使固定增加了40倍，并且在边缘开裂的情况下，羟基磷灰石（HA）植入物的固定上级其钛（Ti）对应物。在所有研究的情况下，移植物改善了固定。我们将研究假设解决三个目标，从以前的资助期的基础上有希望的结果。目的1：通过穿透（破裂）坐骨边缘，为翻修界面提供更大的通路（天然生长因子、细胞、骨髓）。我们将比较边缘开裂与扩孔以移除SB边缘的程序。目的2：通过在翻修种植体表面直接涂覆促进骨生长的涂层，提高天然生长因子和细胞的利用率。目标三：通过局部应用骨移植物和骨移植物替代品，使用和不使用骨髓抽吸物和富血小板血浆（PRP）浓缩物，增强翻修界面。对于目标1，研究的两种入路技术是边缘开裂和扩孔。对于目标2，研究的三种翻修植入物涂层为Ti、HA + RGD和聚D丙交酯（PLDDA）（含TGF β 1和IGF 1）。对于目标3，研究的四种强化是同种异体移植物、珊瑚羟基磷灰石、有和没有骨髓穿刺和PRP。这些治疗的16个配对组将确定治疗的有效性、相互作用和协同作用。结果测量包括组织形态学（%骨面积和植入物接触区和连接性）、micro-CT（包括骨体积、表面积与体积比、各向异性指数）和机械（静态推出强度、刚度、能量和动态阻尼因子和阻尼比）。我们与一位有成就的临床科学家及其团队，以及生物工程师和科学家的积极合作伙伴关系为我们的共同目标带来了多样化的能力。我们的良好合作以及建立和临床验证的实验模型是未来研究的坚实基础，以提高临床上令人烦恼的翻修植入物的寿命。