Supramolecular nanofibers for recombinant growth factor-free spine fusion

项目摘要 排在血液之后，骨骼是最常被移植的组织，在美国有160万到200万例移植手术。 我们每年都独处。脊柱融合术是最常见的需要骨骼的骨科手术之一。 治愈，每年进行超过500,000次治疗。虽然移植病人自己的骨头是 被认为是脊柱融合的黄金标准，它的使用受到供区发病率和不足的挑战。 供骨的可用性。重组骨形态发生蛋白-2(rhBMP-2)是一种 FDA批准作为骨移植替代品，但与使用相关的严重不良反应已导致 患者、医生和医院的重大关切。普遍安全有效的植骨 这些手术目前还不存在脊柱融合术的替代品。我们的长期目标是开发一种 高效无生长因子重组生物活性纳米骨再生策略的研究 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处成骨的细胞信号，使用两种 互补方法：1)我们发现的多肽两亲性纳米纤维的糖基化应用 实现与骨骼相关的宿主衍生生长因子的仿生呈现和增强信号传递 再生；2)第二个发现的应用，即某些多肽纳米纤维设计可以入侵细胞 增强成骨信号的膜。在这项工作中开发的纳米纤维支架将用于 单独或与骨髓基质细胞(BMSC)联合培养，而不是重组生长 因素。我们的研究将通过增强骨形成能力来促进骨的修复和再生 患者自身的自然生长因素。这种方法可以消除对重组因子的需要， 从而为脊柱融合术中的骨再生提供了更安全有效的治疗策略。 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.