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，下背部疼痛就会影响超过6500万人，估计每年耗资100B美元。这些病例中约有1200万例是由于椎间盘（IVD）通过创伤或自然衰老而产生的。此外，椎间盘退化导致遭受损害的生物力学，频繁进展为脊柱动力学，骨关节炎和脊柱不稳定性。许多患者最初对保守治疗（例如抗炎药物）有反应，但大量在短时间内停止反应，这时他们今天的主要治疗选择是侵入性手术。尽管通常开处方，但中等侵入性的手术解决方案，例如椎间盘切除术和椎板切除术，以及更具侵入性的解决方案，例如椎间盘融合和完全椎间盘的替代方案，存在着重要的问题，并且围绕其使用的不确定性。显然，有效的保守治疗和侵入性干预措施之间存在差距。需要一个解决方案，可以微创地应用，同时还可以直接解决问题的根本原因并允许恢复受影响的运动段的生物力学。该提案描述了持续开发合适的材料，以替代椎间盘的核核，从而恢复椎间盘高度和自然盘功能。现有的原理技术是一种新的方法，它从液体中形成没有化学反应的水凝胶。我们的具体目的将解决以下对可注射聚（乙烯基醇）（PVA）系统作为核孔（NP）替代的需求：（i）作为液体前凝胶的存在，可以通过狭窄的指针安全地注入； （ii）在几分钟内在体温和环境下凝胶； （iii）要进行空间填充并抵抗环形撕裂的挤出，（iv）至少生存100万个动态载荷，峰值载荷为3 kN； （v）可以修订另一种治疗方法，例如NP置换，融合或全盘置换。为了实现这一目标，我们将拟议的工作分为三个特定目的：特定目的1：我们将研究浓度，分子量，放射性化和灭菌对一组合适水凝胶的凝胶化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来筛选伽玛灭菌后在SA1中开发的最佳水凝胶制剂。那些通过静态挤出的制剂将受到1万个循环的动态挤压。 具体目标3：我们将使用正在开发中的简单IVD模型，该模型将使所选的配方在生理相关的负载方案中对材料进行100万个循环疲劳测试。此外，在具有故意环形缺陷的IVD模型中，成功的配方也将疲劳。另外，将测试猪功能性脊柱单元（FSU），以便尽早洞悉生物力学的变化。 公共卫生相关性：慢性下背部疼痛在生活中的某个时刻遭受了70％的人口，使美国经济每年的工人赔偿金数十亿美元损失，通常与脊柱椎间盘的退化有关。当今唯一可用的治疗方案是止痛药或涉及关节融合或全盘置换的侵入性手术程序。此处提出的研究将进一步开发一种可取代或增强现有的椎间盘核核的创新注射水凝胶材料，因此将恢复关节的自然生物力学，并防止或延迟或延迟脊柱的进一步变性。