Photografted Zwitterionic Hydrogel Coating Durability for Reduced Foreign Body Response to Cochlear Implants

Abstract

The durability of photografted zwitterionic hydrogel coatings on cochlear implant biomaterials was examined to determine the viability of these antifouling surfaces during insertion and long-term implant usage. Tribometry was used to determine the effect of zwitterionic coatings on the lubricity of surfaces with varying hydration levels, applied normal force, and time frame. Additionally, flexural resistance was investigated using mandrel bending. Ex vivo durability was assessed by determining the coefficient of friction between tissues and treated surfaces. Furthermore, cochlear implantation force was measured using cadaveric human cochleae. Hydrated zwitterionic hydrogel coatings reduced frictional resistance approximately 20-fold compared to uncoated PDMS, which led to significantly lower mean force experienced by coated cochlear implants during insertion compared to uncoated systems. Under flexural force, zwitterionic films resisted failure for up to 60 min of desiccation. The large increase in lubricity was maintained for 20 h under continual force while hydrated. For loosely cross-linked systems, films remained stable and lubricious even after rehydration following complete drying. All coatings remained hydrated and functional under frictional force for at least 30 min in ambient conditions allowing drying, with lower cross-link densities showing the greatest longevity. Moreover, photografted zwitterionic hydrogel samples showed no evidence of degradation and nearly identical lubricity before and after implantation. This work demonstrates that photografted zwitterionic hydrogel coatings are sufficiently durable to maintain viability before, during, and after implantation. Mechanical properties, including greatly increased lubricity, are preserved after complete drying and rehydration for various applied forces. Additionally, this significantly enhanced lubricity translates to significantly decreased force during insertion of implants which should result in less trauma and scarring.

Keywords: antifouling; fibrosis; implant insertion force; lubricity; sensorineural hearing loss.

Figure 1

Chemical structures of (A) sulfobetaine methacrylate (SBMA) (B) carboxybetaine methacrylate (CMBA) and (C) poly(ethylene glycol) dimethacrylate (PEGDMA).

Figure 2

Scanning electron microscope cross-section images of six-month implants of (A) uncoated PDMS and (B–E) CBMA-coated PDMS with indicated cross-linker (XL) percentages. Scale bar and magnification for (A–E). Confocal microscopy z-stack images of 16-day implants immersed in fluorescein (green) are also shown of (F) uncoated and (G) 10 wt % XL CBMA-coated PDMS.

Figure 3

Hematoxylin and eosin staining of (A) uncoated and (B) CBMA-coated (5 wt % cross-linker) PDMS after 6 weeks of incubation in subcutaneous BL/6 Mus musculus tissue and (C) a plot of the significant (p = 0.033) reduction in measured fibrotic capsule thickness when comparing uncoated and CBMA-coated PDMS under the same conditions for (A, B).

Figure 4

Coefficient of friction of uncoated, CBMA-coated, and SBMA-coated PDMS for pristine samples and samples explanted from mice after 3 weeks of incubation measured with tribometry using PBS as immersive solution and sapphire probe setup. Error bar indicates standard error of mean for n ≥ 4.

Figure 5

Coefficient of friction relative to uncoated PDMS for (A) 5 wt % SBMA hydrogel coated PDMS against various guinea pig tissues or nontissue covered steel probe and (B) different hydrogel coatings (percents are cross-linker wt %) or dermis itself against the dermis-covered probe. Uncoated PDMS value for dermis-covered probe 0.301. Error bar indicates standard error of mean for n ≥ 3.

Figure 6

Time for (A) CBMA, (B) SBMA, and (C) PEGMA coatings to reach 10% (T10) and 90% (T90) of the maximum coefficient of the friction value over a range of cross-link densities. Hydrogels were swollen to equilibrium in PBS prior to testing but measured without additional PBS. Error bar indicates standard deviation for n ≥ 3.

Figure 7

Time until failure was noted for hydrogel coatings when subjected to 5 mm diameter mandrel bend test for a range of cross-link densities. Hydrogel coatings were swollen to equilibrium and then exposed to air (allowed to dry) starting at time 0. Error bar indicates standard error of mean for n ≥ 3.

Figure 8

Coefficient of friction for SBMA hydrogels as a function of the cross-linker percent in swollen state immediately after polymerization and following complete desiccation and rehydration. The value for uncoated PDMS error bar indicates standard error of mean for n ≥ 4. Uncoated PDMS had an average value of 0.179.

Figure 9

Average coefficient of friction (relative to uncoated PDMS) for the first and last 100 cycles of a 2500 cycles test of SBMA-coated PDMS as a function of cross-linker percent. The cycle time equates to a total testing period of 1000 min, with sampling occurring over the first and last 40 min. Error bar indicates standard error of mean for n ≥ 4. Average coefficient of friction of for uncoated PDMS was 0.197.

Figure 10

Coefficient of friction for SBMA hydrogels (5 wt % cross-linker) with increasing normal force applied. Uncoated PDMS value for normal force 1 N 0.19. Error bar indicates standard error of mean for n ≥ 4.

Figure 11

Representative image of uncoated (top) and hydrogel-coated (bottom) cochlear implant arrays. The coated array was soaked in a fluorescein solution for better visualization.

Figure 12

Representative force insertion profiles for uncoated and SBMA-coated electrodes depicted over the course of electrode insertion, wherein the lower maximum force and lower overall force over time can be seen for two manufacturers: (A) Array Type 1 and (B) Array Type 2.

Figure 13

(A) Maximum force of insertion during insertions of uncoated (n = 9) and coated (n = 9) human electrode arrays. (B) Area under the curve analysis of the force over the average distance of insertion was found for insertion and averaged as a correlative measure of total work of insertion depicted in microjoules (μJ). The maximum force was significantly reduced (**p < 0.003) and overall work of insertion tended to be reduced, though this was not significant (p = 0.19).