Orchestrating Bone Regeneration on Multiple Scales

在多个尺度上协调骨再生

基本信息

批准号：
7777855
负责人：
PETER X MA
金额：
$ 35.72万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2012-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7777855
关键词：
Achievement Adhesions Angiogenic Factor Animals Architecture Area BMP7 gene Biological Biological Factors Bone Marrow Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Caliber Cell-Matrix Junction Cells Collagen Computer-Aided Design Computer-Assisted Manufacturing Cues Defect Deposition Electrostatics Engineering Environment Fiber Fibroblast Growth Factor 2 Fracture Goals Growth Factor In Vitro Laboratories Lesion Marrow Measures Medical Imaging Modality Modeling Modification Molecular Morphology Mus Nanosphere Natural regeneration Nutrient Operative Surgical Procedures Osteogenesis Outcome Patients Phase Process Rattus Research Personnel Scanning Shapes Signal Transduction Signaling Molecule Solutions Stem cells Stromal Cells Structure Surface Techniques Testing Thick Time Tissue Engineering Tissues United States Vascularization angiogenesis base bone clinical application clinically relevant design extracellular in vitro Assay in vivo nano nanofiber nanometer nanopore nanoscale neovascularization novel osteogenic programs regenerative regenerative agent regenerative therapy release factor repaired scaffold self assembly success tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Bone fractures and defects result in more than 1.3 million surgical procedures each year in the United States. With current therapies, these fractures and defects can be restored to some degree, but far from an ideal solution. Although regenerative agents such as bone morphogenetic proteins (BMPs) have been shown to enhance bone formation when delivered to bone lesions in animal studies, results remain unpredictable for clinical applications. It is likely that the lack of an appropriate 3D scaffold that mimics the natural extracellular environment and supports bone regeneration is detrimental. It is also likely that inappropriate growth factor delivery (time, quantity, localization) confound the achievement of robust success. It is also likely that BMP alone is not sufficient but that additional factors and progenitor cells may be required in order to promote maximal bone regeneration. In addition, angiogenesis in parallel to tissue regeneration is critical to maintaining long-term viability and sustained function of regenerated tissues. Based on these analyses, we hypothesize that predictable and clinically relevant bone regeneration can be achieved by coordinating the biological activities (cells and regulating molecules) with structural cues (scaffold structures). We therefore propose a patient-specific, multi-scaled nano-fibrous scaffold for the delivery of bone marrow stromal cells (MSC) and multiple regenerative factors to engineer vascularized bone. The specific aims are: SA 1. Design "patient-specific" scaffolds with multi-scaled structures for bone regeneration. SA 2. Formulate NS to individually tune BMP? and bFGF release profiles in multi-scaled scaffolds in vitro; and determine the effects of scaffold structure, bFGF and BMP7 temporal release profiles on osteogenesis and angiogenesis in a mouse ectopic model. SA 3. Confirm that the multi-scaled and factor-releasing scaffolds (selected from Aims 1&2) afford a superior environment for vascularized bone regeneration in a rat critical defect model.

描述（由申请人提供）：在美国，骨折和缺陷每年导致超过130万手术程序。使用当前的疗法，这些骨折和缺陷可以在某种程度上恢复，但远非理想的解决方案。尽管在动物研究中，诸如骨形态发生蛋白（BMP）之类的再生剂（BMP）已被证明可以增强骨骼形成，但对于临床应用，结果仍然无法预测。可能缺乏适当的3D支架，即模仿天然细胞外环境并支持骨骼再生是有害的。不适当的生长因子传递（时间，数量，本地化）也很可能会使成功的成就感到困惑。仅凭BMP也可能不够，但是可能需要其他因素和祖细胞以促进最大的骨骼再生。此外，与组织再生并行的血管生成对于维持长期生存力和再生组织的持续功能至关重要。基于这些分析，我们假设可以通过与结构线索（支架结构）协调生物学活性（细胞和调节分子）来实现可预测和临床相关的骨再生。因此，我们提出了一种患者特异性的，多鳞的纳米纤维支架，用于输送骨髓基质细胞（MSC）和多个再生因子，以使工程师的血管化骨骼。具体目的是：SA1。设计“患者特异性”支架，具有多尺度的骨骼再生结构。 SA 2。配方ns以单独调整BMP？和BFGF在体外多尺度脚手架中释放曲线；并确定支架结构，BFGF和BMP7时间释放谱对小鼠异位模型中成骨和血管生成的影响。 SA 3。确认，在大鼠关键缺陷模型中，多量表和释放因子释放的支架（从AIMS 1和2中选择）为血管化骨再生提供了卓越的环境。