An injectable biocompatible hydrogel nucleus pulposus replacement

可注射的生物相容性水凝胶髓核替代物

• 批准号: 7744555
• 负责人: Gavin James Braithwaite
• 金额: $ 7.67万
• 依托单位: CAMBRIDGE POLYMER GROUP, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7744555
• 关键词: Address; Affect; Aging; Alcohols; Analgesics; Anti-Inflammatory Agents; Anti-inflammatory; Barium Sulfate; Biocompatible; Biomechanics; Body Temperature; Cell Nucleus; Chemistry; Chronic low back pain; Crystallization; Defect; Degenerative polyarthritis; Development; Drug Formulations; Environment; Family suidae; Fatigue; Frequencies; Gait; Gel; Height; Hydrogels; In Situ; In Vitro; Injectable; Intervention; Intervertebral disc structure; Joints; Kinetics; Laminectomy; Liquid substance; Living Costs; Low Back Pain; Materials Testing; Measures; Mechanics; Medical Device; Methods; Modeling; Molecular Weight; Motion; Needles; Nerve; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Phase; Plant Roots; Population; Procedures; Process; Productivity; Property; Research; Simulate; Small Business Innovation Research Grant; Solutions; Solvents; Spinal; Sterility; Sterilization for infection control; Structure; Swelling; System; Technology; Temperature; Testing; Time; Trauma; Uncertainty; Vertebral column; Water; Weight-Bearing state; Work; Workers' Compensation; analog; aqueous; base; chemical reaction; cost; crosslink; in vivo; innovation; insight; intervertebral disk degeneration; minimally invasive; novel; nucleus pulposus; particle; prevent; public health relevance; research study; restoration; sound

DESCRIPTION (provided by applicant): Lower back pain affects over 65 million people in the US alone, costing an estimated $100B annually. About 12 million of these cases arise from degeneration of the intervertebral disc (IVD) through trauma or natural aging. Additionally, disc degeneration results in compromised biomechanics with frequent progression to disrupted spinal dynamics, osteoarthritis and spinal instability. Many patients initially respond to conservative treatments such as anti-inflammatory medication but a significant number stop responding within a short period of time, at which point their main treatment option today is invasive surgery. Although commonly prescribed, moderately invasive surgical solutions such as discectomy and laminectomy, and more invasive solutions such as intervertebral fusion and total disc replacement have important problems and uncertainties surrounding their use. Clearly, a gap exists between marginally effective conservative treatments and invasive interventions. A solution is needed that can be applied minimally invasively while also directly addressing the root cause of the problem and allowing restoration of the biomechanics of an affected motion segment. This proposal describes the continued development of a suitable material to replace the nucleus pulposus of a degenerating disc, thereby restoring disc height and natural disc function. The existing principle technology is a novel method that forms a hydrogel from a liquid without a chemical reaction. Our specific aims will address the following requirements for an injectable poly(vinyl alcohol) (PVA) system as a nucleus pulposus (NP) replacement: (i) to exist as a liquid pre-gel that can be injected safely through an narrow gauge needle; (ii) to gel at body temperature and environment within minutes; (iii) to be space-filling and resist extrusion from annular tears, (iv) to survive at least 1 million cycles of dynamic loading with a peak load of 3 kN; and (v) be revisable to another treatment such as NP replacement, fusion or total disc replacement. To achieve this objective, we divide the proposed work into three Specific Aims: Specific Aim 1: We will investigate the effects of concentration, molecular weight, radiopacification and sterilization on the gelation kinetics and mechanical properties of a set of suitable hydrogels. Specific Aim 2: We will use a static extrusion model to screen the optimal hydrogel formulations developed in SA1, after gamma sterilization. Those formulations that pass the static extrusion will be subjected to dynamic extrusion for 100 thousand cycles. Specific Aim 3: We will use a simple IVD model under development that will allow the chosen formulation to be subjected to 1 million cycle fatigue testing of the material in physiologically relevant loading regimes. In addition, the successful formulations will also be fatigued in an IVD model with a deliberate annular defect. In addition, porcine Functional Spine Units (FSUs) will be tested to obtain early insight into changes in biomechanics due to the proposed procedure. PUBLIC HEALTH RELEVANCE: Chronic lower back pain, which afflicts 70% of the population at some point in their lives and costs the U.S. economy billions of dollars per year in worker's compensation and lost productivity, is often associated with degeneration of the intervertebral disc in the spine. The only treatment options available today are either pain medication or invasive surgical procedures involving joint fusion or total disc replacement. The research proposed here will further develop an innovative injectable hydrogel material that can replace or augment the existing intervertebral disc nucleus, and will hence restore the natural biomechanics of the joint and prevent or delay further degeneration of the spine.

描述（由申请人提供）：仅在美国，腰痛就影响了超过6500万人，每年造成的损失估计为1000亿美元。这些病例中约有1200万是由创伤或自然老化导致的椎间盘退变引起的。此外，椎间盘退变导致生物力学受损，经常发展为脊柱动力学破坏、骨关节炎和脊柱不稳定。许多患者最初对消炎药等保守治疗有反应，但相当多的患者在短时间内停止反应，此时他们的主要治疗选择是侵入性手术。中度侵入性手术如椎间盘切除术和椎板切除术，以及更有侵入性的手术如椎间融合术和全椎间盘置换术，虽然是常用的处方，但在其应用方面存在重要的问题和不确定性。很明显，在收效甚微的保守治疗和侵入性干预之间存在着差距。需要一种解决方案，既可以微创应用，又可以直接解决问题的根本原因，并允许恢复受影响运动节段的生物力学。本建议描述了一种合适的材料的持续发展，以取代退变椎间盘的髓核，从而恢复椎间盘高度和自然椎间盘功能。现有的原理技术是一种不用化学反应就能从液体中形成水凝胶的新方法。我们的具体目标是解决可注射聚乙烯醇（PVA）系统作为髓核（NP）替代品的以下要求：(i)作为液体预凝胶存在，可以通过窄规针安全注射；（ii）在体温和环境下在几分钟内凝胶化；（iii）能够填充空间并抵抗环空撕裂的挤压；（iv）在峰值荷载为3kn的情况下，能够承受至少100万次动态加载；(v)可改行其他治疗，如NP置换术、融合或全椎间盘置换术。为了实现这一目标，我们将提出的工作分为三个具体目标：具体目标1：我们将研究浓度，分子量，放射性混浊和灭菌对一组合适水凝胶的凝胶动力学和机械性能的影响。具体目标2：我们将使用静态挤出模型筛选在伽马灭菌后SA1开发的最佳水凝胶配方。通过静态挤压的配方将进行10万次的动态挤压。具体目标3：我们将使用一个正在开发的简单的IVD模型，该模型将允许所选配方在生理相关加载制度下进行材料的100万次循环疲劳测试。此外，成功的配方也将在具有故意环空缺陷的IVD模型中疲劳。此外，将对猪功能性脊柱单元（fsu）进行测试，以获得由于拟议的手术而导致的生物力学变化的早期见解。公共卫生相关性：慢性腰痛通常与脊柱椎间盘退变有关，70%的人在生命的某个阶段受到慢性腰痛的折磨，每年给美国经济造成数十亿美元的工伤赔偿和生产力损失。目前唯一可用的治疗选择是止痛药或包括关节融合或全椎间盘置换术的侵入性外科手术。本文提出的研究将进一步开发一种创新的可注射水凝胶材料，可以替代或增强现有的椎间盘核，从而恢复关节的自然生物力学，防止或延缓脊柱的进一步退变。