Biomimetic, Mussel-inspired, Bioactive Bone Graft Substitute for Spinal Fusion

项目摘要 腰痛是世界范围内导致残疾的主要原因，影响着5亿多人，而且还在不断增加 随着人口的增长和老龄化，这种疾病也越来越普遍。脊柱融合手术，它使邻近的 脊椎，能有效缓解腰背痛和残疾。每年有超过40万美国人接受脊椎手术 融合手术，总住院费用约为130亿美元，是所有外科手术中最高的。 然而，在这些手术中，高达40%的患者会出现假关节或融合失败，即使在“黄金-- 采用“标准”治疗方法，即从患者自身的髂骨植骨。我们相信组织工程学， 这涉及到工程支架、生长因子和/或细胞的组合来协调新组织 形成，可以解决假关节的问题。目前，Inuse骨移植是唯一的组织 含有FDA批准用于脊柱融合的生长因子的工程产品，尽管具有显著的 设计限制：(1)生长因子的非受控、超生理突发性释放，(2)不良血管 诱导，以及(3)生物不同的设计；所有这些都限制了新骨的形成。在此，我们建议 开发一种专门为克服这些限制而设计的新型骨移植替代品。中环 该项目的假设是，可以设计出一种仿生的、以贻贝为灵感的生物活性骨移植替代品。 提供可控的早期和持续释放血管内皮生长因子(VEGF)和血小板 衍生生长因子(PDGF)，与当前的黄金标准和 临床前动物模型中的Inuse骨移植。在目标1中，我们将为以下目的开发和优化该材料 体外最大的血管生长和骨形成，在目标2中，我们将评估我们的材料在 临床前兔腰椎后外侧融合模型与现行金标准的比较 和Inuse骨移植。我们期待我们的工程移植物将带来更好的融合结果。我们的 研究可能会为未来材料的开发提供信息和/或支持旨在解决 脊柱融合术中的假关节问题。

Project Summary Low back pain is the worldwide leading cause of disability, affecting more than half a billion people and increasing in prevalence alongside a growing and ageing population. Spinal fusion surgery, which immobilizes adjacent vertebrae, can effectively relieve low back pain and disability. Over 400,000 Americans annually undergo spinal fusion surgeries, at an aggregate hospital cost of around $13 billion, the highest of any surgical procedure. However, pseudo-arthrosis, or failed fusion, occurs in up to 40% of these procedures, even when the “gold- standard” treatment of grafting bone from the patient’s own iliac crest is used. We believe tissue engineering, which involves a combination of engineered scaffolds, growth factors, and/or cells to orchestrate new tissue formation, can solve the problem of pseudo-arthrosis. At present, the Infuse Bone Graft is the only tissue engineered product involving a growth factor that is FDA-approved for spinal fusion, though with significant design limitations: (1) non-controlled, supraphysiologic burst release of growth factors, (2) poor vascular induction, and (3) bio-disparate design; all of which limit new bone formation. Herein, we propose the development of a novel bone graft substitute specifically designed to overcome these limitations. The central hypothesis of this project is that a biomimetic, mussel-inspired, bioactive bone graft substitute can be engineered to provide controllable early and sustained release of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF), leading to superior fusion outcomes compared to the current gold standard and the Infuse Bone Graft in a preclinical animal model. In Aim 1, we will develop and optimize this material for maximal vascular ingrowth and bone formation in vitro, and in Aim 2 we will evaluate our material’s efficacy in a preclinical rabbit model of posterolateral lumbar spinal fusion in direct comparison to the current gold standard and the Infuse Bone Graft. We expect that our engineered graft will lead to superior fusion outcomes. Our research may inform the development of future materials and/or support clinical trials aimed at solving the problem of pseudo-arthrosis in spinal fusion.