Implantable Biodegradable RF-Powered Tissue Stimulator and Electrodes

描述（由申请人提供）：用于医疗应用的植入式可生物降解电子设备提供了在有限的时间内（几周到几个月）提供治疗或监测功能的潜力，根据应用的预期需求在注册中降解，因此不需要手术移除。然而，仍有许多技术有待开发，以实现实际的生物可降解电子系统。该R21的目标是开发完全可生物降解的射频（RF）发电机和刺激电极，作为实现各种手术植入的可生物降解电子设备的新平台技术。发电机和电极将根据电气规范和形式进行设计，并与生物可降解脊柱融合刺激器相兼容，作为该技术的范例应用。我们的新方法将是使用基于生物相容性和生物可吸收的镁合金导电和电阻元件的射频线圈电路，并使用相同的合金作为电极的材料。使用临床使用的现有不可降解脊柱融合刺激器的电气规格作为指导，我们将设计、制造和测试射频线圈电路和刺激电极，以提供恒流刺激。干细胞对刺激电极的增殖和分化反应将在体外进行评估，并与对常规不可降解电极的反应进行比较。评估电极降解和组织相容性的试点实验将在一个固定的硬连线皮下大鼠模型中进行体内评估。射频线圈电路的功能和耦合效率将在体外模拟体液中进行评估。随着时间的推移，通过确认预测的细胞反应和组件功能，这些目标的成功完成将为后续研究解决组件优化和完整系统开发奠定基础，包括与有源电子设备的集成，以及在动物脊柱融合模型中进行测试。

DESCRIPTION (provided by applicant): Implantable biodegradable electronic devices for medical applications offer the potential to provide therapeutic or monitoring functions for limited periods of time - weeks to months - degrading in register with the anticipated needs of the application and thus not requiring surgical removal. However, numerous technologies remain to be developed to enable practical biodegradable electronic systems. The goal of this R21 is to develop completely biodegradable radio frequency (RF) power generators and stimulating electrodes as novel platform technology for enabling a variety of surgically implantable biodegradable electronic devices. The generators and electrodes will be designed according to electrical specifications and forms that are compatible with their incorporation into a biodegradable spinal fusion stimulator as a paradigm application of this technology. Our novel approach will be to use RF coil circuits based on biocompatible and bioresorbable magnesium alloy conductive and resistive components, and also use this same alloy as the material for the electrodes. Using the electrical specifications of existing, non-degradable spinal fusion stimulators in clinical use for guidelines, we will design, fabricate, and test RF coil circuits and stimulating electrodes to deliver constant current stimulation. Stem cell proliferative and differentiative responses to the stimulating electrodes will be assessed in vitro and compared with responses to conventional non-degradable electrodes. Pilot experiments to assess electrode degradation and tissue compatibility will be assessed in vivo in a tethered hard-wired subcutaneous rat model. Functionality and coupling efficiency of the RF coil circuit will be assessed in vitro in simulated body fluid. Successful completion of these aims, as demonstrated by confirming predicted cellular responses and component functionalities over time, will establish the basis for follow-on research addressing component optimizations and complete system development, including integration with active electronics, and testing in an animal spinal fusion model. PUBLIC HEALTH RELEVANCE: The objective of this study to demonstrate feasibility of key components for implantable biodegradable electronic devices that need only function temporarily, such as an electrical stimulator for spinal fusion, or in more general terms, for stimulating repair and remodeling of tissue engineered constructs, fractures, or grafts. This technology would make electrical stimulation a more practical and acceptable therapeutic option by overcoming the barriers to clinical acceptance of permanent implants that only need to function for relatively short periods of time after implantation and may require surgical removal at the end of their service life.