Supramolecular nanofibers for recombinant growth factor-free spine fusion

项目摘要 在血液之后，骨是最常移植的组织，在美国进行了160万至200万次移植。 美国每年都。脊柱融合术是最常见的骨科手术， 治愈，每年超过50万例。虽然移植病人自己的骨头 被认为是脊柱融合的金标准，其使用受到供体部位发病率和不充分的挑战。 供体骨的可用性。重组骨形态发生蛋白-2（rhBMP-2）是一种生长因子， FDA批准作为骨移植替代品，但与其使用相关的严重不良反应已引起 患者、医生和医院的重大关切。普遍安全有效的植骨 目前还不存在用于这些手术的脊柱融合的替代物。我们的长期目标是发展一个 使用无重组生长因子生物活性纳米材料的高效骨再生策略 材料，适用于脊柱融合和其他骨科应用。我们将通过以下方式实现这一目标： 实施多轴策略以改善骨缺损部位的成骨细胞信号传导，使用两个 互补方法：1）应用我们的发现，肽两亲物纳米纤维的糖基化 实现了骨中所涉及的宿主衍生生长因子的仿生呈递和增强的信号传导 再生; 2）应用第二个发现，即某些肽的设计可以侵入细胞， 膜以增强成骨信号传导。在这项工作中开发的支架将用于 单独使用或与骨髓基质细胞（BMSC）联合使用，而不是与重组生长 因子我们的研究将通过增强骨形成能力，促进骨的修复和再生。 病人自身的生长因子这种方法可以减少对重组因子的需求， 从而为脊柱融合中的骨再生提供更安全和更有效的治疗策略， 其他骨科应用。

Project Summary After blood, bone is the most frequently transplanted tissue, with 1.6 to 2 million transplants performed in the US alone each year. Spine fusions are among the most common orthopaedic procedures requiring bone healing, with over 500,000 performed annually. Although transplantation of the patient's own bone is considered the gold standard for spine fusion, its use is challenged by donor site morbidity and inadequate availability of donor bone. Recombinant bone morphogenetic protein-2 (rhBMP-2) is a growth factor that is FDA-approved as a bone graft substitute, but serious adverse effects associated with its use have caused significant concerns by patients, physicians, and hospitals. Universally safe and effective bone graft substitutes for spine fusion do not currently exist for these procedures. Our long-term goal is to develop a highly effective strategy to regenerate bone using recombinant growth factor-free bioactive nanoscale materials, suitable to spine fusion and other orthopaedic applications. We will achieve this goal by implementing a multiaxial strategy to improve cell signaling for osteogenesis at the bone defect site, using two complimentary approaches: 1) application of our discovery that glycosylation of peptide amphiphile nanofibers achieves biomimetic presentation and enhanced signaling of host-derived growth factors involved in bone regeneration; 2) application of a second discovery that certain peptide nanofiber designs can invade cell membranes to enhance osteogenic signaling. The nanofiber scaffold developed in this work will be used either on its own or in combination with bone marrow stromal cells (BMSC) rather than with recombinant growth factor. Our studies will facilitate the repair and regeneration of bone by enhancing the bone-forming capacity of a patient's own native growth factors. Such an approach could obviate the need for recombinant factors, thereby providing a safer and more effective therapeutic strategy for bone regeneration in spinal fusion and other orthopaedic applications.