Biological Surface Modification for Implantable medical devices

Assisting patients with debilitating neurological problems such as Lou Gerhig’s disease (amytrophic lateral sclerosis) or Parkinson’s disease provides an immense challenge for biomedical researchers. The effectiveness of pharmaceutical approaches is limited by the efficient action of the blood-brain barrier. More recently, implantable devices for the brain have been approved.¹⁹ For Parkinson’s patients, these devices provide therapeutic electrical stimulation that seems to interrupt tremor-generating neural circuits to provide some relief to patients. However, over time, these devices tend to lose their efficacy. One likely contributor to their failure is a build-up of scar tissue formation around the electrode site. Thus, one active area of biomedical materials research is the development of novel implantable materials and/or coatings that have the capability to extend the effective life of implantable devices in the brain. In general, such approaches utilize biologically-based techniques to ‘lure’ neurons into close proximity to the implanted devices.^20-22 The simplest technique employs biological surfaces coatings that neurons find attractive.²³ The approach is a natural extension of work done in the life sciences for creating more effective Petri dish surfaces in which to grow cells

In this REU project, undergraduates will join an existing team of graduate students already developing a new class of implantable device in the Neural Engineering Device Development Laboratory of Dr. Rousche. The new device is manufactured using a polyimide substrate. While ongoing experiments are aimed at polyimide process development, later experiments will determine effective biological coatings compatible with the polyimide surface chemistry. REU undergraduates will be assigned the task of developing suitable surface modification/adhesion processes for candidate peptides (specific amino acid sequences that serve as adhesion markers for cells). Peptides will be manufactured to specification by the Research Resource Laboratory. SIKVAV and RDG have proven useful as coatings for cell culture and will be employed here as candidate device surface coatings. Each of these peptides and potentially others will each require development of a polyimide-specific surface processing routine, including reactive ion etching and silanization. An additional challenge will be for the REU students to develop processing steps compatible with implantable medical devices (low temperature, non-toxic etc.) REU undergraduates will characterize this processing and evaluate the resulting surface properties using techniques such as Fourier transform infrared spectroscopy and spectroscopic ellipsometry.

References

19. Kennedy, P. R. and Bakay, R. A., "Restoration of neural output from a paralyzed patient by a direct brain connection," Neuroreport, vol. 9, no. 8, pp. 1707, June 1998.

20. Kimpinski K, Campenot RB, Mearow K., “Effects of the neurotrophins nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures,” J Neurobiol. 1997 Oct;33(4):395.

21. McCaig, C.D., Rajnicek, A.M., Song, B., and Zhao, M. 2002. “Has electric growth cone guidance found its potential?” Trends Neurosciences, 25(7): 354. 2002.

22. Rajnicek, A, Kenneth R. Robinson, and Colin D. McCaig S. The Direction of Neurite Growth in a Weak DC Electric Field Depends on the Substratum: Contributions of Adhesivity and Net Surface Charge. Developmental Biology, vol. 203, pp. 412 1998.

23. Huber M, Heiduschka P, Kienle S, Pavlidis C, Mack J, Walk T, Jung G, Thanos S. Modification of glassy carbon surfaces with synthetic laminin-derived peptides for nerve cell attachment and neurite growth. J Biomed Mater Res. 1998 Aug;41(2):278