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Functional Fluid Flow Regulated Bone Regeneration

功能性流体流量调节骨再生

基本信息

批准号：
9128747
负责人：
Yi-Xian Qin
金额：
$ 35.11万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9128747
关键词：
3-Dimensional Affect Animal Model Biochemistry Bioreactors Birds Blood Circulation Blood Vessels Bone Marrow Stem Cell Bone Regeneration Bone Substitutes Bone Surface Bone Tissue Bone Transplantation Cell Culture Techniques Cell Differentiation process Cell Proliferation Cell Survival Cell Transplantation Cells Clinical Cultured Cells Defect Dose Endosteum Engineering Environment Equation Finite Element Analysis Fourier Transform Frequencies Geometry Goals Growth Healed Health Healthcare Histology Homing Immature Bone In Vitro Knowledge Liquid substance Marrow Measures Mechanics Mediating Mediator of activation protein Modality Modeling Muscle Natural regeneration Nutrient Operative Surgical Procedures Osteoblasts Osteogenesis Osteopenia Outcome Oxygen Patients Perfusion Periosteum Permeability Phase Physiologic calcification Physiological Porosity Quality of life Recruitment Activity Regulation Role Signal Transduction Solid Spatial Distribution Stimulus Synchrotrons Techniques Tissue Engineering Tissue Grafts Uncertainty Vascularization Waste Products base bone bone cell bone healing calcification design fluid flow healing implantation improved in vivo mineralization novel novel strategies osteogenic osteoporosis with pathological fracture pressure response scaffold shear stress stem cell differentiation tissue regeneration tissue repair ulna

项目摘要

DESCRIPTION (provided by applicant): Traumatic and osteoporotic fractures, critical/large defects and nonunion represent a significant burden in health care and affects quality of life for these patients. Tissue engineering approaches show promise as bone substitutes, and have been particularly successful in vitro in a bioreactor environment. The major challenge of tissue engineered regeneration is to maintain viability of cells in vivo and to rebuild vascular networks capable of delivering oxygen and nutrients while removing waste products after the implantation. Recently, a new cell homing approach has shown promising results in recruiting endogenous cells and then regeneration without cell transplantation. To accelerate cell homing and maintain cell viability in vivo, functional bone fluid flow induced by mechanical loading has been shown to be a critical regulator in initiating and mediating bone surface and osteonal adaptation. Dynamic fluid flow through porous constructs will exert increased fluid shear stress to promote in vivo cell differentiation and mineralization. Using oscillatory pressurized marrow fluid flow and muscle-bone interface stimuli, small magnitude fluid pressure (10-60 mmHg) with relative high frequency and short daily duration (10min) was found to initiate new bone formation and mitigate increased intracortical porosities caused by disuse osteopenia. It is essential to establish a functional dynamic fluid flow environment within the in vivo porous bone large defect and maintain an active fluid flow for bone regeneration. Thus, we will examine the general hypothesis that functional mechanotransduction regulated by dynamic bone fluid flow, with optimized intensity and rate, is essential and responsible for in vivo tissue regeneration, cellular differentiation, and osteogenic mineralization in critical defect healing. The ultimate gol is to generate an oscillatory fluid pressure gradient in the critical defect and the scaffold, servng as an in vivo bioreactor to promote functional fluid flow, vascular circulation, and osteogenesis. The outcomes will improve our understanding of how an optimized fluid flow environment enhances cellular viability and mineralization, and the importance of mechanotransduction in tissue repair and regeneration particularly under in vivo conditions. It is expected that this project will provide a novel approach to regulate bone formation via in vivo fluid flow stimuli, an improve our knowledge of critical signals for dynamic mechanotransduction in accelerating bone formation and mineralization in tissue regeneration, which will be ultimately used for clinical tissue repair.

描述（由申请人提供）：创伤性和骨质疏松性骨折，严重/大缺损和骨不连是医疗保健的重要负担，并影响这些患者的生活质量。组织工程方法显示出作为骨替代品的前景，并在体外生物反应器环境中取得了特别成功。组织工程再生的主要挑战是维持细胞在体内的活力，重建能够输送氧气和营养的血管网络，同时清除植入后的废物。最近，一种新的细胞归巢方法在募集内源性细胞并在不进行细胞移植的情况下进行再生方面显示出了良好的效果。为了加速细胞在体内的归巢和维持细胞活力，机械负荷诱导的功能性骨液流动已被证明是启动和介导骨表面和骨适应的关键调节因子。通过多孔结构的动态流体流动将施加增加的流体剪切应力，以促进体内细胞分化和矿化。通过振荡加压骨髓液流动和肌肉-骨界面刺激，小幅度的流体压力（10-60 mmHg），相对高频率和较短的每日持续时间（10min）被发现启动新骨形成和减轻由废骨减少引起的皮质内孔隙增加。在体内多孔骨大缺损内建立功能性的动态流体流动环境，保持活跃的流体流动是骨再生的必要条件。因此，我们将检验由动态骨液流动调节的功能机械转导的一般假设，以优化的强度和速率，对体内组织再生、细胞分化和关键缺陷愈合中的成骨矿化至关重要。最终目标是在关键缺陷和支架中产生振荡流体压力梯度，作为体内生物反应器，促进功能性流体流动、血管循环和成骨。该结果将提高我们对优化流体流动环境如何提高细胞活力和矿化的理解，以及机械转导在组织修复和再生中的重要性，特别是在体内条件下。该项目将提供一种通过体内流体刺激调节骨形成的新方法，提高我们对加速骨形成和组织再生矿化的动态机械转导关键信号的认识，最终将用于临床组织修复。