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

项目摘要 下背痛是世界范围内导致残疾的主要原因，影响着超过5亿人， 随着人口的增长和老龄化，脊柱融合手术，固定相邻的 脊椎，可以有效缓解腰痛和残疾。每年有超过40万美国人接受脊柱手术 融合手术，总医院成本约为130亿美元，是所有外科手术中最高的。 然而，假关节，或失败的融合，发生在高达40%的这些程序，即使当“黄金- 使用从患者自身髂嵴移植骨的“标准”治疗。我们相信组织工程， 它包括工程支架、生长因子和/或细胞的组合， 形成，可以解决假关节的问题。目前，灌注植骨是唯一的组织 一种含有生长因子的工程产品，FDA批准用于脊柱融合术，尽管具有显著的 设计局限性：（1）生长因子的非受控、超生理性爆发释放，（2）血管不良 诱导和（3）生物不同设计;所有这些都限制了新骨形成。在此，我们建议 开发一种专门设计用于克服这些局限性的新型骨移植替代物。中央 该项目假设是可以设计仿生的、贻贝启发的、生物活性的骨移植替代物 提供血管内皮生长因子（VEGF）和血小板的可控的早期和持续释放， 衍生生长因子（PDGF），与当前金标准相比，融合结局上级， 在临床前动物模型中植入骨移植物。在目标1中，我们将开发和优化这种材料， 最大的血管长入和骨形成在体外，在目标2中，我们将评估我们的材料的有效性， 后外侧腰椎融合术的临床前兔模型与当前金标准的直接比较 和灌注植骨我们希望我们的工程移植物将导致上级融合结果。我们 研究可以为未来材料的开发提供信息和/或支持旨在解决这些问题的临床试验。 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.