Polyurethane Bone Cements for Total Hip Implants

描述(由申请人提供)：自20世纪60年代S以来，聚甲基丙烯酸甲酯(PMMA)一直被用作全髋关节置换术(THA)中的骨水泥，至今仍在全球每年进行的150万全髋关节置换手术中使用。尽管PMMA有很长的临床历史，但骨科界承认PMMA的缺点，其中包括放热、任何未反应单体的毒性、纤维组织的包裹以及骨水泥-植入物界面强度[1][2]。这项建议将重点放在后一点，即水泥-种植体(或水泥-金属)界面强度。这种界面的局部脱粘会引发一系列事件：微动、颗粒碎片生成、巨噬细胞活动、骨吸收，最后是植入物的无菌性松动。人们试图改善PMMA的界面强度，但收效甚微，这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]。使用以聚氨酯(PUR)为基础的粘固剂提供了一种完全不同的方法来解决这一临床问题。马刺的生物稳定性和生物兼容性的记录可以追溯到几十年前[4]。最近，原位固化PUR粘合剂配方已被引入欧洲市场，并被临床用作骨空洞填充物和固定骨折。这些以PUR为基础的粘固剂已被证明与骨和金属有很强的粘结性。随着这些材料临床经验的增长，人们对用于全关节置换装置固定的PUR骨水泥的开发产生了浓厚的兴趣。这项研究建议开发一种专为全髋关节生物力学要求而设计的PUR骨水泥。该项目的第一阶段将包括利用聚合物化学的基本结构-性能原理来配制新的PURS，以提供一种反应性两部分系统，该系统在混合后可在24小时内实现完全承载性能、与骨和金属植入物的强大粘附性以及长期的生物稳定性。然后，这些配方将接受机械测试，以全面了解它们的性能。在第一阶段中，特别感兴趣的将是它们与THA装置和骨的粘附性。这些材料将同时接受静态和动态测试方案，在实验室模型中复制活体载荷。同时，新材料将接受体外生物稳定性测试，以表征原位氧化降解的风险，这将限制其临床生存能力。此外，还将评估已开发的PURS的可提取单体水平，并与PMMA进行比较。这些测试的首要目标是评估每种材料作为临屋区PMMA替代品的潜力。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、附着力和生物稳定性，并完成生物兼容性测试，在更复杂的载荷下进行机械评估，最终用于人类临床。 公共卫生相关性：该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附性骨水泥。这种聚甲基丙烯酸甲酯的替代品将在水泥和金属装置之间具有优异的粘接强度，显著降低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。

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.