R01:Biomimetic Surface for Neural Implant PI: Tracy Cui Implantable microelectrode arrays for neural recording and stimulation have demonstrated tremendous research and clinical potential. Studies of brain tissue response to neural electrode arrays have revealed localized microglia activation, followed by astrocytic scarring and neural degeneration. These reactions are thought to contribute to the low yield and chronic failure of neural recording, although direct links have not been soundly established. Past studies characterizing the CNS response to implants have used postmortem histology at discrete time points. This approach suffers from a large degree of variability and fails to capture the dynamic molecular, cellular and vascular changes of the host. To address this issue, we have developed an experimental set-up to directly image the electrode-tissue interface in live animals using 2-photon microscopy in conjunction with electrical recording. Our previous work indicates that by coating the surface of neural probes with neural adhesion molecules, neuronal density around the device can be promoted while glial reaction attenuated. Meanwhile, neural recording quality is drastically improved. We hypothesize that promoting neuronal growth and health, and/or inhibiting microglia activation will lead to recording improvement. The specific objectives of thi project are to investigate the biological mechanisms of the coating's effect on recording and to evaluate the clinical potential of biomimetic coating in a brain machine interface (BMI) model. First, the acute neuronal and microglia responses to coated probes will be characterized in transgenic animals using two photon imaging and electrical recording for two weeks. Real time tissue characteristics (such as neuronal and neurite density, microglia density and morphology, vasculature change and BBB leakage) will be correlated to recording metrics(such as unit yield, SNR, amplitude of signal and noise as well as impedance). Several biomolecules that promote or inhibit neuronal growth or microglia activation will be immobilized on the Blackrock arrays to test our hypothesis. Secondly, the long-term benefit of the coatings on recording will be determine by testing the optimum coating conditions in rats for 6 months. Explants will be taken monthly to examine the coating longevity, while immunohistochemistry and microarray analysis of the tissue at the interface will be performed to characterize the cellular and molecular change over time. Thirdly, to assess the potential of biomimetic coating for clinical application, coated electrodes will be tested in rhesus monkeys in a brain-machine-interface (BMI) model. Recording metrics such as SNR, signal amplitude, unit yield and stability will be quantified over 2 years and compared to uncoated arrays. A novel functional metric will be developed to assess functionality of the recorded signals. BMI performance will be evaluated based on speed and accuracy. This proposal combines the cutting edge real-time imaging, effective biomaterial strategies and state of the art brain machine interface technology to understand the interactions between neural implants and host tissue. The findings will guide the development of seamless neural interface devices for BMI, visual and auditory prosthesis, deep brain stimulation for Parkinson's disease, depression and epilepsy, to name a few. The knowledge will also benefit other brain implants from biochemical sensing and therapeutic delivery to scaffold and stem cell transplant for treating neurological disorders.

Public Health Relevance

Microdevices can be placed in the brain to restore function and treat neurological disease. The goal of this project is to investigate the novel approaches that can be taken to make the implanted device seamlessly integrate with the brain tissue and thereby obtain improved performance longevity and reliability.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01NS062019-05A1
Application #
8761947
Study Section
(BNVT)
Program Officer
Ludwig, Kip A
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kozai, Takashi D Y; Li, Xia; Bodily, Lance M et al. (2014) Effects of caspase-1 knockout on chronic neural recording quality and longevity: insight into cellular and molecular mechanisms of the reactive tissue response. Biomaterials 35:9620-34
Weaver, Cassandra L; LaRosa, Jaclyn M; Luo, Xiliang et al. (2014) Electrically controlled drug delivery from graphene oxide nanocomposite films. ACS Nano 8:1834-43
Azemi, Erdrin; Lagenaur, Carl F; Cui, Xinyan T (2011) The surface immobilization of the neural adhesion molecule L1 on neural probes and its effect on neuronal density and gliosis at the probe/tissue interface. Biomaterials 32:681-92
Luo, Xiliang; Weaver, Cassandra L; Zhou, David D et al. (2011) Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation. Biomaterials 32:5551-7
Luo, Xiliang; Matranga, Christopher; Tan, Susheng et al. (2011) Carbon nanotube nanoreservior for controlled release of anti-inflammatory dexamethasone. Biomaterials 32:6316-23
Luo, Xiliang; Cui, Xinyan Tracy (2011) Electrochemical deposition of conducting polymer coatings on magnesium surfaces in ionic liquid. Acta Biomater 7:441-6
Azemi, Erdrin; Gobbel, Glenn T; Cui, Xinyan Tracy (2010) Seeding neural progenitor cells on silicon-based neural probes. J Neurosurg 113:673-81
Luo, Xiliang; Cui, Xinyan Tracy (2009) Sponge-like nanostructured conducting polymers for electrically controlled drug release. Electrochem commun 11:1956