Supramolecular nanofibers for recombinant growth factor-free spine fusion

用于重组无生长因子脊柱融合的超分子纳米纤维

基本信息

批准号：
9904125
负责人：
SAMUEL I STUPP
金额：
$ 63.2万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-12 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9904125
关键词：
3-Dimensional Adverse effects Allografting Architecture Autologous Autologous Transplantation Binding Biocompatible Materials Biological Biomedical Engineering Biomimetics Blood Bone Marrow Bone Matrix Bone Regeneration Bone Transplantation Cell Therapy Cell membrane Cells Ceramics Collagen Collagen Type I Defect Development Dose Evaluation Extracellular Matrix FDA approved Goals Gold Growth Factor Health Care Costs Healthcare Heparitin Sulfate Hospitals Human Hybrids Hydration status In Situ Injections Invaded Lead Membrane Membrane Microdomains Modeling Monosaccharides Morbidity - disease rate Orthopedic Procedures Orthopedics Oryctolagus cuniculus Osteogenesis Pathway interactions Patients Peptides Physicians Procedures Proteins Rattus Receptor Signaling Recombinant Growth Factor Recombinants Regenerative Medicine Reporting Signal Transduction Site Source Spinal Fusion Spine surgery Stromal Cells Sulfate System Tissue Transplantation Transplant Recipients Transplantation Treatment Efficacy Vertebral column Work aqueous base bone bone healing bone morphogenetic protein 2 bone quality clinical care clinically relevant comparative cost design glycosylation improved improved mobility insight lipophilicity nano nanofiber nanoscale novel osteogenic polysulfated glycosaminoglycan pre-clinical recombinant human bone morphogenetic protein-2 repaired scaffold surgery outcome synergism

项目摘要

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.

项目摘要血液后，骨骼是最常见的移植组织，在每年我们一个人。脊柱融合是需要骨头的最常见的骨科手术之一治愈，每年进行500,000多次。尽管患者自身的骨骼移植是被认为是脊柱融合的黄金标准，其使用受到供体现场发病率和不足的挑战供体骨骼的可用性。重组骨形态发生蛋白2（RHBMP-2）是生长因子 FDA批准为骨移植物替代品，但与使用相关的严重不利影响已引起患者，医生和医院的重大关注点。普遍安全有效的骨移植目前，对于这些程序，目前不存在替代脊柱融合的替代品。我们的长期目标是开发使用无重组生长因子的生物活性纳米级的高效策略来再生骨骼材料，适合脊柱融合和其他骨科应用。我们将通过使用两个免费方法：1）应用我们发现的发现肽两亲纳米纤维的糖基化实现植物衍生生长因子的仿生表现和增强的信号传导再生; 2）应用第二发现，即某些肽纳米纤维设计可以入侵细胞膜增强成骨信号传导。这项工作中开发的纳米纤维脚手架将被使用本身或与骨髓基质细胞（BMSC）结合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骼的修复和再生患者自己的本地生长因素。这种方法可以消除重组因素的需求，从而为脊柱融合和其他骨科应用程序。