Polyurethane Bone Cements for Total Hip Implants

用于全髋关节植入物的聚氨酯骨水泥

• 批准号: 7904349
• 负责人: Ibrahim Sendijarevic
• 金额: $ 15.56万
• 依托单位: TROY POLYMERS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904349
• 关键词: Address; Adhesions; Adhesives; Affect; Arthroplasty; Back; Benchmarking; Biocompatible Materials; Biological; Biomechanics; Bone Cements; Bone Resorption; Canada; Chemicals; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Complex; Contracts; Data; Development; Devices; Drug Formulations; Elderly; Elements; Embolism; Engineering; Environment; Europe; European; Evaluation; Event; Failure; Fatigue; Femoral Fractures; Filler; Fracture; Generations; Goals; Hip region structure; Hour; Human; Implant; In Situ; In Vitro; Laboratories; Life; Maintenance; Marketing; Mechanics; Medical Device; Metals; Methods; Modeling; Modification; Names; Operative Surgical Procedures; Orthopedics; Particulate; Patients; Performance; Phase; Poison; Polymer Chemistry; Polymers; Polymethyl Methacrylate; Polyurethanes; Procedures; Process; Property; Protocols documentation; Recording of previous events; Records; Regulatory Pathway; Replacement Arthroplasty; Reporting; Research; Research Design; Research Personnel; Resistance; Risk; Scientist; Simulate; Solutions; Structure; Surgeon; System; Technology; Testing; Thick; Time; Tissues; Total Hip Replacement; Toxic effect; Validation; Walking; Weight-Bearing state; Work; base; biomaterial compatibility; biomechanical engineering; bone; clinical application; commercialization; design; experience; follow-up; hip replacement arthroplasty; improved; in vivo; interest; macrophage; manufacturing process; monomer; physical model; polymethacrylic acid; pressure; public health relevance; success

DESCRIPTION (provided by applicant): Polymethylmethacrylate (PMMA) has been used as a bone cement in total hip arthroplasty (THA) since the 1960's and today is still used in a significant percentage of the 1.5 million THA procedures performed worldwide each year. Despite its long clinical history the orthopaedic community acknowledges shortcomings with PMMA including among other things its exotherm, the toxicity of any unreacted monomer, its encapsulation by fibrous tissue and its cement-implant interface strength [1][2]. This proposal will focus on the later point, the cement-implant (or cement-metal) interface strength. Local debonding at this interface initiates a cascade of events; micromotion, particulate debris generation, macrophage activity, bone resorption and finally aseptic loosening of the implant. Attempts have been made to improve the interface strength of PMMA, but gains have been marginal, leading researchers to conclude that it's not an issue of if the interface should fail but when [3]. The use of polyurethane (PUR) based cement provides a completely different approach to addressing this clinical problem. PURs have a proven record of biostability and biocompatibility going back several decades [4]. More recently, in situ curing PUR adhesive formulations have been introduced to European markets and are seeing clinical use as bone void fillers and in stabilizing fractures. These PUR based cements have been shown to provide strong bond to bone and metal. As clinical experience with these materials grows, there is significant interest in development of PUR bone cement for affixation of total joint replacement devices. This research proposes development of a PUR bone cement specifically engineered for the biomechanical demands of THA. Phase 1 of the project will include formulation of new PURs using fundamental structure- property principles of polymer chemistry to provide a reactive two part system that upon mixing achieves full load bearing properties within 24 hour, strong adhesion to bone and metal implants, and long-term biostability. These formulations will then undergo mechanical testing to gain a full understanding of their capabilities. Of specific interest in Phase 1 will be their adhesion to THA devices and bone. The materials will be subjected to both static and dynamic test protocols, reproducing in vivo loads in a laboratory model. In parallel, the new materials will undergo in vitro biostability testing to characterize the risk of in situ oxidative degradation that would limit its clinical viability. Furthermore, level of extractable monomers will be evaluated for developed PURs and compared to PMMA. The overarching objective of these tests is to assess each material's potential as a replacement for PMMA in THA. Later phases of the project would include further refinement of the leading candidate material to improve load bearing capability, adhesion, and biostability, and to complete biocompatibility testing, mechanical assessment under more complex loading, and ultimately human clinical use. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to develop a polyurethane adhesive bone cement for use in total hip replacement surgery. This alternative to polymethylmethacrylate will have superior bond strength between the cement and the metal device, significantly reducing the risk of failure due to loosening at this interface. The technology developed in this study has the potential to improve the lives of over 1.5 million new patients each year who undergo hip replacement surgeries.

描述（由申请人提供）：自20世纪60年代以来，聚甲基丙烯酸甲酯（PMMA）已被用作全髋关节置换术（THA）中的骨水泥，目前在全球每年进行的150万例THA手术中仍占很大比例。尽管PMMA的临床应用历史悠久，但骨科界承认其存在缺点，包括其可吸收性、任何未反应单体的毒性、纤维组织对其的包封以及骨水泥-植入物界面强度[1][2]。本建议将重点关注后一点，即骨水泥-植入物（或骨水泥-金属）界面强度。该界面处的局部脱粘引发一连串事件;微动、颗粒碎片生成、巨噬细胞活性、骨吸收和最终植入物的无菌性松动。已经尝试提高PMMA的界面强度，但收益很小，导致研究人员得出结论，这不是界面是否应该失效的问题，而是何时失效的问题[3]。聚氨酯（PUR）骨水泥的使用为解决这一临床问题提供了一种完全不同的方法。PUR具有数十年来证明的生物稳定性和生物相容性记录[4]。最近，原位固化PUR粘合剂配方已被引入欧洲市场，并在临床上用作骨空隙填充物和稳定骨折。这些基于PUR的骨水泥已被证明可提供与骨和金属的牢固结合。随着这些材料的临床经验的增长，人们对开发用于固定全关节置换器械的PUR骨水泥产生了极大的兴趣。本研究建议开发一种专门设计用于THA生物力学要求的PUR骨水泥。该项目的第1阶段将包括使用聚合物化学的基本结构-性能原理配制新的PUR，以提供一种反应性两部分系统，该系统在混合后在24小时内实现完全承载性能、与骨和金属植入物的强粘附性以及长期生物稳定性。然后，这些配方将进行机械测试，以充分了解其性能。第1阶段的特别关注点是它们与THA器械和骨的粘附。材料将接受静态和动态试验方案，在实验室模型中再现体内载荷。同时，新材料将进行体外生物稳定性测试，以表征原位氧化降解的风险，这将限制其临床可行性。此外，将评价开发的PUR的可浸提单体水平，并与PMMA进行比较。这些测试的首要目标是评估每种材料在THA中替代PMMA的潜力。该项目的后期阶段将包括进一步完善领先的候选材料，以提高承载能力，粘附力和生物稳定性，并完成生物相容性测试，在更复杂的负载下进行机械评估，并最终用于人类临床。 公共卫生相关性：本项目的总体目标是开发一种用于全髋关节置换手术的聚氨酯粘合剂骨水泥。这种聚甲基丙烯酸甲酯的替代品在骨水泥和金属器械之间具有上级粘合强度，显著降低了由于该界面松动而导致的失效风险。这项研究开发的技术有可能改善每年超过150万接受髋关节置换手术的新患者的生活。