COMPLAINT POLYMER LUMBAR ARTIFICIAL DISC PRECLINICAL STUDY

投诉聚合物腰椎人工椎间盘临床前研究

• 批准号: 7562470
• 负责人: KAREN S RICE
• 金额: $ 0.63万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562470
• 关键词: Animals; Autopsy; Biological; Buprenex; Carbonates; Cardiology; Catheters; Cell Nucleus; Class; Clinical; Codeine; Computer Retrieval of Information on Scientific Projects Database; Device Safety; Devices; Drug Formulations; Elastomers; Europe; Event; Femur; Fluoroscopy; Fright; Funding; General Anesthesia; General Population; Gold; Grant; Hardness; Hip Joint; Histology; Histopathology; Hour; Hydrocarbons; Image; Immunohistochemistry; Implant; Inflammation; Institution; International; Low Back Pain; Mechanics; Medical; Medical Device; Metals; Monitor; Movement; Operative Surgical Procedures; Organ; Orthopedics; Outcome; Pacemakers; Pain; Papio; Patients; Plague; Polyethylene; Polyethylenes; Polymers; Polyurethanes; Positioning Attribute; Postoperative Period; Protasul 100; Recording of previous events; Research; Research Personnel; Resources; Roentgen Rays; Score; Site; Slide; Societies; Source; Spinal; Spinal Fusion; Standards of Weights and Measures; Stress; Surface; System; Technology; Testing; Time; Tissues; Today; Tylenol; United States Food and Drug Administration; United States National Institutes of Health; Urethane; Vertebral column; Week; Wound Healing; base; calcium phosphate coating; concept; cytokine; cytotoxicity test; oxidation; particle; polycarbonate; pre-clinical; preclinical study; sample fixation; spine bone structure; success; vertebra body

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Spine ailments are among the most common and costly illnesses of society today. In the US alone, 30 billion dollars annually are spent on the surgical treatment of low back pain. About 400,000 such surgeries are performed every year. Until recently the 'gold standard' has been to perform a spine fusion. In 2005 FDA cleared for the first time a mechanical total disc replacement (TDR) device to be freely sold in the US (more devices are expected in 2006). Mechanical TDR devices, however, are feared by experts not to have the hoped (and praised) long-term advantages when compared with traditional spinal fusion. Adjacent level degeneration, known to exist as a result of fusion, may still persist as an adverse outcome of disc replacement surgery. In addition, new complications such as poorly guided movements between vertebral bodies causing pain or small wear particles originating from the implant surfaces causing inflammation and ultimately implant loosening may plague the patient. A new artificial disc concept, a so-called "compliant disc", that would potentially not have the above shortcomings, shall be tested in a baboon study for its clinical suitability. The CAdisc implant is comprised of three polycarbonate polyurethane formulations of different hardness for annulus, nucleus and end plate. The end plates have a thin coating of calcium phosphate. A 'pilot' baboon study was performed in May 2006 when a preclinical device was implanted in a single subject. The animal, under administration of routine pain killers (Buprenex and Tylenol /w codeine) recovered from surgery within hours, showing normal movements and activity. The postoperative time frame was event free. Weekly radiographs documented a stable implant position. Necropsy showed progress in wound healing concomitant with the time frame. The Ranier formulations and the coating have been subjected to cytotoxicity testing and the coated end plate material was also used in implants for a 12 week ovine femur study without ill effect. Moreover, polycarbonate polyurethanes are a well understood class of materials, with considerable history in medical devices. They were one of the first classes of polyurethane materials promoted for their biostability. They are thermoplastic elastomers with carbonate linkages adjacent to hydrocarbon groups which give this class of materials oxidative stability, making the polymers attractive for medical device applications where oxidation is a potential mode of degradation. In addition, polycarbonate polyurethanes have been shown to minimize surface degradation such as stress induced microfissures. Three commercial grades of polycarbonate urethanes are in use as part of approved medical applications, including Bionate¿ (the Polymer Technology Group), Carbothane¿ (Noveon) and ChronoFlex¿ C (CardioTech International). Polycarbonate polyurethanes are used in a wide variety of cardiology applications, including LVADs, pacemakers and catheters. Several commercialized orthopedic implant products employ polycarbonate polyurethane. These include the Zimmer Dynesys, a dynamic neutralization system for the spine, which is composed of Protasul 100 pedicular screws, Sulene-PET cords and Sulene-PCU (polycarbonate polyurethane) spacers. The first Dynesys device was implanted in Europe in 1994 and has treated over 9,000 patients. Last year, Dynesys outsold the Charite disc in the US. Implant began to commercialize new hip joint implants based on a proprietary polycarbonate urethane in Europe in 2000. A master file is registered with the US Food & Drug Administration. Animals will be physically examined before surgery and again before release into the general population. Under general anesthesia, they will undergo surgery of the spine lasting about 2 hours. A CAdisc implant will be placed in the prepared space between two adjacent lumbar vertebral bodies and its positioning confirmed under fluoroscopy. The post-operative stability of the devices will be monitored at intervals by X-ray analyses. During the survival period the tissue of the vertebral bony end plates is expected to integrate with the adjacent device end plates. Bony integration is required for the longer term fixation of the implant and explants will be assessed using Faxitron and/or micro-CT imaging and histomorphometry. The success criteria for the study are device stability within the product specification without significant pain. Histology of organs and tissues will be employed to assess the biological safety of the device. Immunohistochemistry of cytokines will be performed to evaluate inflammation local to the implant site. All histopathology slides will be scored for the presence of particles associated with the device. Should the CAdisc implant prove to be a valid option to presently used artificial disc implants featuring sliding metal-on-metal or metal-on-polyethylene surfaces, complications or adverse outcomes associated with these types of implant (induced adjacent level degeneration, sudden and painful give-away episodes for spinal movements known as "clinical instability," lack of axial cushioning, small wear particles causing inflammation, etc.) could be avoided.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 脊柱疾病是当今社会最常见和最昂贵的疾病之一。仅在美国，每年就有300亿美元用于下背痛的手术治疗。每年约有40万例此类手术。直到最近，“黄金标准”一直是进行脊柱融合。2005年，FDA首次批准了机械全椎间盘置换（TDR）器械在美国自由销售（更多器械 预计2006年）。 然而，专家们担心，与传统的脊柱融合术相比，机械TDR器械不会有所希望的（和赞扬的）长期优势。已知融合导致的相邻节段退变仍可能作为椎间盘置换术的不良结局持续存在。此外，新的并发症，如椎体之间的不良引导运动导致疼痛或植入物表面产生的小磨损颗粒导致炎症并最终导致植入物松动，可能会困扰患者。一种新的人工椎间盘概念，即所谓的“顺应性椎间盘”，可能不具有上述缺点，应在狒狒研究中对其临床适用性进行测试。 CAdisc植入物由三种不同硬度的聚碳酸酯聚氨酯配方组成，用于瓣环、髓核和终板。终板上有一层薄薄的磷酸钙涂层。在2006年5月进行了一项“试点”狒狒研究，当时将临床前器械植入单个受试者体内。给予常规止痛药（布普瑞奈和泰诺/w可待因）的动物在数小时内从手术中恢复，显示出正常的运动和活动。 术后时间范围无事件。每周X线片记录了稳定的植入物位置。尸检显示随着时间的推移，伤口愈合有所进展。 Ranier配方和涂层已经过细胞毒性试验，涂层终板材料也用于12周绵羊股骨研究的植入物中，没有不良反应。 此外，聚碳酸酯聚氨酯是一种众所周知的材料，在医疗器械中具有相当长的历史。它们是因其生物稳定性而被推广的第一类聚氨酯材料之一。它们是具有与烃基相邻的碳酸酯键的热塑性弹性体，这赋予这类材料氧化稳定性，使得聚合物对于其中氧化是潜在降解模式的医疗器械应用具有吸引力。此外，聚碳酸酯聚氨酯已被证明可以最大限度地减少表面降解，如应力诱导的微裂缝。三种商业等级的聚碳酸酯树脂作为批准的医疗应用的一部分正在使用，包括Bionate <$（聚合物技术集团），Carbothane <$（Noveon）和ChronoFlex <$C（ChronoTech International）。 聚碳酸酯聚氨酯用于各种心脏病学应用，包括LVAD、起搏器和导管。几种商业化的骨科植入物产品采用聚碳酸酯聚氨酯。其中包括Zimmer Dynesys，一种用于脊柱的动态中和系统，由Protasul 100椎弓根螺钉、Sulene-PET线和Sulene-PCU（聚碳酸酯聚氨酯）间隔器组成。第一台Dynesys器械于1994年在欧洲植入，已治疗了9,000多名患者。去年，Dynesys在美国的销量超过了Charite光盘。Implant于2000年开始在欧洲将基于专有聚碳酸酯聚氨酯的新型髋关节植入物商业化。主文件在美国食品和药物管理局注册。 在手术前对动物进行体格检查，并在释放至一般群体前再次进行体格检查。在全身麻醉下，他们将接受持续约2小时的脊柱手术。将CAdisc植入物放置在两个相邻腰椎椎体之间准备好的间隙中，并在X线透视下确认其位置。将通过X线分析定期监测器械的术后稳定性。 在存活期内，预计椎骨骨终板的组织将与相邻器械终板整合。植入物的长期固定需要骨整合，将使用Faxitron和/或显微CT成像和组织形态计量学评估取出物。本研究的成功标准是器械稳定性符合产品质量标准，无明显疼痛。将采用器官和组织的组织学来评估器械的生物安全性。将进行细胞因子的免疫组织化学，以评价植入部位局部的炎症。将对所有组织病理学切片进行器械相关颗粒的评分。 如果CAdisc植入物被证明是目前使用的具有滑动金属对金属或金属对聚乙烯表面的人工椎间盘植入物的有效选择，则与这些类型的植入物相关的并发症或不良结局（诱导相邻节段退变，称为“临床不稳定”的脊柱运动的突然和疼痛泄露事件，缺乏轴向缓冲，引起炎症的小磨损颗粒等）。是可以避免的。