COMPLAINT POLYMER LUMBAR ARTIFICIAL DISC PRECLINICAL STUDY

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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.