Cochlear implant (CI) electrode arrays are made of platinum wires and contacts encased in a silastic housing. These materials provide mechanical stability and flexibility critical to the long-term function of the device. However, they also induce local tissue reactions that can have detrimental effects. For example, the fibrotic capsule that encases CI electrode arrays leads to increased impedances and signal broadening which decreases the effectiveness of the device. Further, intracochlear fibrosis is implicated in the loss of acoustic hearing that can occur months to years after implantation. Beyond fibrosis, bacterial adhesion to CI materials can lead to infection and often requires removal of the CI. Thus, developing materials that mitigate the fibrous response and bacterial adhesion to CI materials could significantly improve device function and safety. Ultra- low fouling zwitterionic polymers are a new class of materials that show significant promise to eliminate fibrosis and bacterial adhesion. However as bulk materials they lack mechanical properties and long term durability suitable for use in CIs. To leverage the ultra-low fouling surface properties of zwitterionic polymers while maintaining the proven mechanical properties of current CI materials, we recently developed a novel photochemical process for simultaneous polymerization, grafting and cross-linking of durable zwitterionic thin films on relevant CI materials. We hypothesize that durable, cross-linked zwitterionic thin film coatings generated through photopolymerization will maintain long-term anti-fouling properties, direct cell growth, and dramatically reduce fibrosis and bacterial adhesion.
In Aim 1, the effect of cross-link density on mechanical stability and durability will be examined by increasing molecular weight and concentration of the cross-linker. To elucidate the direct relationship between cross-link density and anti-fouling properties, protein adsorption and cell adhesion will be assessed. The inherent spatial control of photopolymerization enables precise patterning of the thin films. Accordingly, Aim 2 examines the effect of photopatterned zwitterionic coatings to spatially control cell adhesion (fibroblasts and astrocytes) and alignment (Schwann cells and spiral ganglion neurons, SGNs). Further, the impact of coating patterning on intracochlear fibrosis and ossification, hearing levels, and hair cell and SGN counts will be assessed. Finally, Aim 3 determines the ability of zwitterionic coatings to resist bacterial adhesion and persistence. The efficacy of these coatings on three different bacterial types, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, will be assessed both in vitro and in vivo. Development of adherent and durable zwitterionic thin film coatings on polymers (e.g. silastic, polyurethanes, polyethylene, etc.) and metals (e.g. platinum, titanium, etc.) represents a transformative advance to improve the function and reduce the infection risk associated with placement of medical devices in the body.
Although cochlear implants represent the most successful neuroprosthesis in clinical use, the materials used to make the implant induce scarring in the cochlea that has detrimental effects on device function. Further, cochlear implants, like other medical implants, can become infected by bacteria. Here we develop a novel technology based on photochemistry to provide thin film coatings of cochlear implant materials that dramatically reduce scarring and bacterial infection. The results will also inform efforts to improve functional outcomes and reduce infection risk in a wide variety of medical devices.
|Truong, Kristy; Ahmad, Iram; Jason Clark, J et al. (2018) Nf2 Mutation in Schwann Cells Delays Functional Neural Recovery Following Injury. Neuroscience 374:205-213|
|Tuft, Bradley W; Xu, Linjing; Leigh, Braden et al. (2018) Photopolymerized micropatterns with high feature frequencies overcome chemorepulsive borders to direct neurite growth. J Tissue Eng Regen Med 12:e1392-e1403|
|Xu, Linjing; Seline, Alison E; Leigh, Braden et al. (2018) Photopolymerized Microfeatures Guide Adult Spiral Ganglion and Dorsal Root Ganglion Neurite Growth. Otol Neurotol 39:119-126|
|Leigh, Braden L; Truong, Kristy; Bartholomew, Reid et al. (2017) Tuning Surface and Topographical Features to Investigate Competitive Guidance of Spiral Ganglion Neurons. ACS Appl Mater Interfaces 9:31488-31496|
|Leigh, Braden L; Cheng, Elise; Xu, Linjing et al. (2017) Photopolymerizable Zwitterionic Polymer Patterns Control Cell Adhesion and Guide Neural Growth. Biomacromolecules 18:2389-2401|
|Cheng, Elise L; Leigh, Braden; Guymon, C Allan et al. (2016) Quantifying Spiral Ganglion Neurite and Schwann Behavior on Micropatterned Polymer Substrates. Methods Mol Biol 1427:305-18|
|Li, Shufeng; Tuft, Bradley; Xu, Linjing et al. (2016) Intracellular calcium and cyclic nucleotide levels modulate neurite guidance by microtopographical substrate features. J Biomed Mater Res A 104:2037-48|
|Li, Shufeng; Tuft, Bradley W; Xu, Linjing et al. (2015) Microtopographical features generated by photopolymerization recruit RhoA/ROCK through TRPV1 to direct cell and neurite growth. Biomaterials 53:95-106|
|Kopelovich, Jonathan C; Reiss, Lina A J; Etler, Christine P et al. (2015) Hearing Loss After Activation of Hearing Preservation Cochlear Implants Might Be Related to Afferent Cochlear Innervation Injury. Otol Neurotol 36:1035-44|
|Tuft, Bradley W; Xu, Linjing; White, Scott P et al. (2014) Neural pathfinding on uni- and multidirectional photopolymerized micropatterns. ACS Appl Mater Interfaces 6:11265-76|
Showing the most recent 10 out of 12 publications