Failure Mechanisms of Revision Joint Replacement

修正关节置换术的失效机制

• 批准号: 7730381
• 负责人: Joan E Bechtold
• 金额: $ 26.74万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730381
• 关键词: 3-Dimensional; Adherence; Allografting; Anabolic Agents; Anisotropy; Anti-Inflammatory Agents; Anti-inflammatory; Area; Autologous; Autologous Transplantation; Bilateral; Blood Vessels; Bone Growth; Bone Tissue; Bone Transplantation; Clinical; Clinical Research; Complex; Defect; Drug or chemical Tissue Distribution; Experimental Models; Failure; Frequencies; Funding; Goals; Gold; Growth; Growth Factor; HA coating; Healed; Healthcare; Hip region structure; Histologic; Hospitals; Human; Hydroxyapatites; IGF1 gene; Immunohistochemistry; Implant; Improve Access; In Situ; Infection; Infection prevention; Inferior; Intervention; Knee; Knowledge; Left; Life Expectancy; Literature; Longevity; Maintenance; Marrow; Measures; Mechanics; Methods; Modeling; Motion; Operative Surgical Procedures; Outcome; Outcome Measure; Paired Comparison; Parathyroid Hormones; Patients; Periosteum; Pharmaceutical Preparations; Plasma; Polyethylenes; Procedures; Process; Quality of life; Quantitative Evaluations; Randomized; Replacement Arthroplasty; Resources; Risk; Sample Size; Secure; Shear Strength; Side; Site; Staining method; Stains; Stimulus; Strontium; Structure; Surface; Surgeon; Techniques; Thick; Time; Tissues; Titanium; Training; Vascular Endothelial Cell; Work; allogenic bone transplantation; antimicrobial; antimicrobial drug; base; bisphosphonate; bone; bone growth factor; bone loss; care burden; case-based; cell growth; cost; density; healing; human PTH protein; implant coating; implantable device; implantation; improved; indexing; particle; prevent; primary outcome; public health relevance; recombinant human bone morphogenetic protein-2; sample fixation; success

DESCRIPTION (provided by applicant): Our long term goal is to improve the clinical success of revised joint replacements by improving their fixation. We developed our experimental model of revision joint replacement in an earlier funding period, and established its correspondence with clinical studies. We have shown that interventions yielding superior fixation of primary implants do not uniformly improve fixation of revision implants. This is due in large part to the devitalized sclerotic bone shell that typically forms during aseptic loosening. The smooth and relatively impermeable surface of the sclerotic bone barrier reduces shear attachment strength and acts as a barrier to the transport of cells and growth factors. Earlier we established that creating access across the barrier by a surgical technique ("cracking" the barrier) markedly improves fixation. In the last period we established that the clinical technique of reaming to remove the sclerotic barrier results in inferior fixation compared with cracking. For this funding period we have three aims, all with sclerotic bone barrier cracking; (i) to evaluate anabolic and anti-catabolic agents when access of the body's own marrow and blood vessels is established by sclerotic bone cracking, (ii) to apply multi-drug coatings with antimicrobial agents and growth factors and (iii) to augment bone graft with periosteum and synthetic bone graft extenders. We hypothesize (1) that grafted anabolic and anticatabolic agents will improve implant fixation, (2) that an antimicrobial coating does not impair fixation, and that fixation is improved when it is combined with an anabolic agent, and (3) that bone graft extenders (autologous periosteum and bioactive hydroxyapatite) will improve fixation compared with control. Fixation is determined mechanically (static and dynamic shear strength, stiffness and energy and damping modulus), histomorphometrically (bone ongrowth, % bone in peri-implant space, % fibrous tissue and % marrow at implant surface and in peri-implant space). Vascular growth is quantified with immunohistochemistry. While primary joint replacements provide the highest quality of life improvement per health care dollar spent, and have 95% survival at ten years, the number of revisions for failed primaries is rising due to the increasing pool of people with implanted devices and having longer life spans. The health care burden of revision surgery is high and rising: revisions comprise 20% of joint replacement surgeries, are complex and require specialized surgeon and hospital resources, have poorer function, and are more likely to become infected. Costs are expected to reach $50 billion in 2015, a rise of roughly 400% since 2005. PUBLIC HEALTH RELEVANCE: Our long term goal is to improve the clinical success of revised joint replacements by improving their fixation. We have three main approaches; (i) to improve the access of the body's own marrow and blood vessels, (ii) to apply multi-drug coatings with antimicrobial agents and growth factors, and (iii) to augment bone graft with periosteum and synthetic bone graft extenders. Revision implants comprise 20% of joint replacement surgeries and costs are expected to reach $50 billion in 2015, a rise of roughly 400% since 2005.

描述（由申请人提供）：我们的长期目标是通过改善固定来提高翻修关节置换术的临床成功率。我们在较早的资助期开发了翻修关节置换的实验模型，并建立了与临床研究的对应关系。我们已经证明，初次植入物上级固定的干预措施并不能均匀地改善翻修植入物的固定。这在很大程度上是由于通常在无菌性松动过程中形成的失活骨壳。骨屏障的光滑和相对不可渗透的表面降低了剪切附着强度，并作为细胞和生长因子转运的屏障。早期我们已经证实，通过手术技术（“破坏”屏障）创建穿过屏障的通路可显著改善固定。在最后一个阶段，我们确定了与开裂相比，通过扩髓来去除骨屏障的临床技术导致固定较差。在本资助期内，我们有三个目标，均与骨屏障开裂有关;（i）当通过骨屏障开裂建立人体自身骨髓和血管通路时，评估合成代谢和抗分解代谢药物，（ii）应用含抗菌剂和生长因子的多药涂层，（iii）用骨膜和合成骨移植扩展剂增强骨移植。我们假设（1）移植的合成代谢和抗分解代谢药物将改善植入物固定，（2）抗菌涂层不会损害固定，当与合成代谢药物联合使用时，固定得到改善，（3）与对照组相比，骨移植延长剂（自体骨膜和生物活性羟基磷灰石）将改善固定。通过机械（静态和动态剪切强度、刚度和能量以及阻尼模量）、组织形态学（骨生长、植入物周围间隙中的骨%、植入物表面和植入物周围间隙中的纤维组织%和骨髓%）确定固定。用免疫组织化学定量血管生长。虽然初次关节置换术提供了最高的生活质量改善每卫生保健美元花费，并有95%的生存率在10年，失败的初次翻修的数量正在上升，由于越来越多的人植入设备，并具有更长的寿命。翻修手术的医疗保健负担很高，而且还在上升：翻修手术占关节置换手术的20%，复杂，需要专业的外科医生和医院资源，功能较差，更容易感染。预计2015年成本将达到500亿美元，自2005年以来增长约400%。 公共卫生相关性：我们的长期目标是通过改善固定来提高翻修关节置换术的临床成功率。我们有三个主要的方法;（i）改善人体自身骨髓和血管的进入，（ii）应用具有抗菌剂和生长因子的多药物涂层，以及（iii）用骨膜和合成骨移植扩展剂增加骨移植。翻修植入物占关节置换手术的20%，预计2015年成本将达到500亿美元，自2005年以来增长约400%。