Electrotherapeutic strategies for connective tissue repair

结缔组织修复的电疗策略

基本信息

批准号：
8319344
负责人：
Clark T. Hung
金额：
$ 64.57万
依托单位：
TUFTS UNIVERSITY MEDFORD
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8319344
关键词：
Adjuvant Therapy Animal Model Animals Applications Grants Biochemical Bioreactors Bone Regeneration Bone Tissue Bone Transplantation Cartilage Cell Proliferation Cell membrane Cell physiology Cells Chondrogenesis Clinic Clinical Connective Tissue Defect Development Devices Electric Stimulation Embryonic Development Engineering Environment Family Feedback Fracture Gene Proteins Generations Growth Factor Healed Human In Vitro Ion Channel Ion Pumps Ions Liquid substance Maps Mechanics Medical Device Membrane Potentials Methods Microfluidics Modality Modeling Molecular Molecular Genetics Musculoskeletal Natural regeneration Osteogenesis Outcome Pathway interactions Perfusion Phase Play Population Rattus Regenerative Medicine Regulation Research Design Role Signal Transduction Spinal Fusion Staging Stimulus System Technology Testing Thick Tissue Engineering Tissue Grafts Tissues Translating Validation bone bone engineering cartilage regeneration cartilage repair cell behavior design electric field electrical potential healing high throughput screening human adult stem cell implantation improved in vivo insight interest migration model design novel novel strategies osteochondral tissue repaired stem cell differentiation tissue regeneration tissue repair tool voltage

项目摘要

DESCRIPTION (provided by applicant): The role that biophysical forces play in regenerative medicine is expanding, with increased interest in the use of intrinsic electrical forces (via regulation of cell membrane channels) and externally applied electric fields (via bioreactor environments) as important control points. Despite significant potential of electrical signals for regenerative medicine, they have not yet been integrated into the design of tissue engineering systems. We propose a radically new strategy to improve connective tissue regeneration by electrotherapeutic control of cell function, through the integrated use of molecular and electrical control of cell function and tissue formation. Our hypothesis is that the synergistic application of molecular control of transmembrane ion flux and externally applied electric fields will improve the quality of cartilage and bone regeneration and accelerate their integration in vivo. We will rigorously test this hypothesis by studying the regeneration of composite bone/cartilage grafts. The regulation of cell function and tissue regeneration will be first studied in vitro using controlled bioreactor environments, and then in vivo in an orthotropic animal model of cartilage and bone regeneration. Three specific aims will be pursued: (a) Biophysical regulation of chondrogenesis and osteogenesis in adult human stem cells, (b) Electrotherapeutic bioreactor models for regeneration of cartilage/bone tissues, and (c) Animal studies of cartilage/bone regeneration. The anticipated scientific impact will be in significant new insights into the biophysical control of connective tissue repair by modulation of electrical regulatory signals. The main technological impact will be in improved regeneration of cartilage/bone tissues, and the new generation of electrotherapeutic medical devices termed BioDomes.

描述（由申请人提供）：生物物理力在再生医学中发挥的作用正在扩大，对使用内在电气的使用（通过调节细胞膜通道）和外部应用的电场（通过生物反应器环境）增加了兴趣，作为重要的控制点。尽管电信号对再生医学的潜力很大，但尚未将它们整合到组织工程系统的设计中。我们提出了一种新的新策略，以通过对细胞功能的分子和电气控制的细胞功能和组织形成的分子控制和电气控制来改善细胞功能的结缔组织再生。我们的假设是，跨膜离子通量和外部施加的电场的分子控制的协同应用将提高软骨和骨骼再生的质量，并加速其在体内的整合。我们将通过研究复合骨/软骨移植物的再生来严格检验这一假设。首先使用受控生物反应器环境在体外研究细胞功能和组织再生的调节，然后在软骨和骨再生的正性动物模型中进行体内。将追求三个具体目的：（a）成人人干细胞中软骨发生和成骨的生物物理调节，（b）软骨/骨组织再生的电性生物反应器模型，以及（c）软骨/骨骼再生的动物研究。预期的科学影响将是通过调节电信号的调节对结缔组织修复的生物物理控制的重大见解。主要的技术影响将是改善软骨/骨组织的再生，以及称为生物构想的新一代电学医学设备。