- Perhaps the most important problem limiting the performance and utility of electronic biomedical devices that are implanted in tissue is the reactive response near the electrode that limits performance over extended periods of time. In the cortex, this is known to involve the activation of microglia and astrocytes, and the associated die-off of target cells (neurons) in a region of ~100 microns proximal to the probe surface. Strategies to overcome this problem have included the use of anti-inflammatory agents and neurotrophic factors. However, it is not clear that inflammatory agents will work over the long term. Attracting the neurons to the electrode is also a strategy that may not work well, since the inorganic electrode surface represents an interface between the hard metallic or semiconducting engineered device and the much softer organic tissue, and is thus inevitably a mechanically unstable environment that is dangerous for cell viability. It would therefore be useful if there were some alternative means to create nanoscale, electronically active filaments that were an extension of the metal electrodes, providing an efficient means of communication across the reactive scar and out into the surrounding tissue. Here we propose a method that may accomplish this by the direct, in- vivo polymerization of conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT). PEDOT is a conjugated polymer that is effective at facilitating charge transport between metallic electrodes and ionically conductive tissue. In previous work in our laboratory, we have shown that PEDOT coatings can help to improve the performance of biomedical devices such as microfabricated cortical probes in vivo. We have also demonstrated that PEDOT can be electrochemically polymerized around living cells both in-vitro and in-vivo. In slice cultures, we have shown that PEDOT can be grown out and into cortical tissue for 1000 microns or more, much larger than the ~100 micron size typical of the reactive cell layer. However many questions remain about the detailed methods of polymerization, including monomer delivery rates, influence of healing, and the viability and remodeling of cells in the polymerization zone. In this project we will investigate the in-vivo polymerization of PEDOT into living tissue, and will evaluate its impact on the performance of the biomedical devices of interest. We will investigate the role of wound healing around the probe on the subsequent polymerization and associated cell physiology in the reactive zone by waiting for different periods of time before initiating the reaction. We will focus our attention on microfabricated cortical electrodes of interest to the Center for Neural Communications Technology at the University of Michigan, directed by Daryl Kipke. This method has the potential to revolutionize the performance of a wide variety of implantable electronic biomedical devices including cortical probes, retinal implants, deep brain stimulators, and cardiac pacemakers. If this novel research eventually proves to be successful, there is considerable potential to move these methods from the laboratory to further development. Certain aspects of this work are related to inventions disclosed to the University of Michigan Technology Transfer Office, and under commercial development by Biotectix LLC, a spin-off company. Prof. Martin is a Co- Founder and Chief Scientific Officer for Biotectix LLC (www.biotectix.com).
This project describes the design and evaluation of materials and methods for improving the integration of hard, inert, electronic biomedical devices with soft, ionically- conducting living cortical tissue via the direct polymerization of conducting polymers. These methods may help improve the long-term performance of microfabricated cortical electrodes. This work also has implications for the design and performance of a wide variety of therapeutic medical devices including peripheral nerve interfaces, cochlear implants, and cardiac pacemakers.
|Ouyang, Liangqi; Wei, Bin; Kuo, Chin-Chen et al. (2017) Enhanced PEDOT adhesion on solid substrates with electrografted P(EDOT-NH2). Sci Adv 3:e1600448|
|Wei, Bin; Liu, Jinglin; Ouyang, Liangqi et al. (2017) POSS-ProDOT Crosslinking of PEDOT. J Mater Chem B 5:5019-5026|
|Liu, Jinglin; Lin, David Y; Wei, Bin et al. (2017) Single Electrospun PLLA and PCL Polymer Nanofibers: Increased Molecular Orientation with Decreased Fiber Diameter. Polymer (Guildf) 118:143-149|
|Qu, Jing; Ouyang, Liangqi; Kuo, Chin-Chen et al. (2016) Stiffness, strength and adhesion characterization of electrochemically deposited conjugated polymer films. Acta Biomater 31:114-121|
|Cho, Whirang; Wu, Jinghang; Shim, Bong Sup et al. (2015) Synthesis and characterization of bicontinuous cubic poly(3,4-ethylene dioxythiophene) gyroid (PEDOT GYR) gels. Phys Chem Chem Phys 17:5115-23|
|Wei, Bin; Liu, Jinglin; Ouyang, Liangqi et al. (2015) Significant enhancement of PEDOT thin film adhesion to inorganic solid substrates with EDOT-acid. ACS Appl Mater Interfaces 7:15388-94|
|Ouyang, Liangqi; Kuo, Chin-Chen; Farrell, Brendan et al. (2015) Poly[3,4-ethylene dioxythiophene (EDOT) -co- 1,3,5-tri[2-(3,4-ethylene dioxythienyl)]-benzene (EPh)] copolymers (PEDOT-co-EPh): optical, electrochemical and mechanical properties. J Mater Chem B 3:5010-5020|
|Ouyang, Liangqi; Shaw, Crystal L; Kuo, Chin-Chen et al. (2014) In vivo polymerization of poly(3,4-ethylenedioxythiophene) in the living rat hippocampus does not cause a significant loss of performance in a delayed alternation task. J Neural Eng 11:026005|
|Wu, Jinghang; Cho, Whirang; Martin, David C et al. (2013) Highly Aligned Poly(3,4-ethylene dioxythiophene) (PEDOT) Nano- and Microscale Fibers and Tubes. Polymer (Guildf) 54:702-708|
|King, Zachary A; Shaw, Charles M; Spanninga, Sarah A et al. (2011) Structural, chemical and electrochemical characterization of poly(3,4-ethylenedioxythiophene) (PEDOT) prepared with various counter-ions and heat treatments. Polymer (Guildf) 52:1302-1308|