Electrotherapeutic strategies for connective tissue repair

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，对使用内在电力（通过调节细胞膜通道）和外部施加电场（通过生物反应器环境）作为重要控制点的兴趣增加。尽管电信号在再生医学中具有巨大的潜力，但它们尚未被整合到组织工程系统的设计中。我们提出了一种全新的策略，通过整合使用分子和电控制细胞功能和组织形成，通过电疗控制细胞功能来改善结缔组织再生。我们的假设是，跨膜离子通量的分子控制和外部施加的电场的协同应用将提高软骨和骨再生的质量，并加速它们在体内的整合。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。细胞功能和组织再生的调节将首先在体外使用受控的生物反应器环境进行研究，然后在体内在软骨和骨再生的正交各向异性动物模型中进行研究。将追求三个具体目标：（a）成人干细胞中软骨形成和骨形成的生物物理调节，（B）软骨/骨组织再生的电疗生物反应器模型，和（c）软骨/骨再生的动物研究。预期的科学影响将是通过调节电调节信号对结缔组织修复的生物物理控制的重要新见解。主要的技术影响将是改善软骨/骨组织的再生，以及称为BioDomes的新一代电疗医疗设备。

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.