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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：
10152362
负责人：
SAMUEL I STUPP
金额：
$ 62.24万
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/10152362
关键词：
3-Dimensional Adverse effects Allografting Architecture Autologous Autologous Transplantation BMP2 gene 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 Vertebral column Work aqueous base bone bone healing 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 therapeutically effective

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.

项目总结