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

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.

Assessing Leachable Cytotoxicity of 3D-Printed Polymers and Facile Detoxification Methods.

Additive manufacturing of polymers is gaining momentum in health care industries by providing rapid 3D printing of customizable designs. Yet, little is explored about the cytotoxicity of leachable toxins that the 3D printing process introduced into the final product. We studied three printable materials, which have various mechanical properties and are widely used in stereolithography 3D printing. We evaluated the cytotoxicity of these materials through exposing two fibroblast cell lines (human and mouse derived) to the 3D-printed parts, using overlay indirect contact assays. All the 3D-printed parts were measured toxic to the cells in a leachable manner, with flexible materials more toxic than rigid materials. Furthermore, we attempted to reduce the toxicity of the 3D-printed material by employing three treatment methods (further curing, passivation coating, and Soxhlet solvent extraction). The Soxhlet solvent extraction method was the most effective in removing the leachable toxins, resulting in the eradication of the material's toxicity. Passivation coating and further curing showed moderate and little detoxification, respectively. Additionally, mechanical testing of the materials treated with extraction methods revealed no significant impacts on its mechanical performances. As leachable toxins are broadly present in 3D-printed polymers, our cytotoxicity evaluation and reduction methods could aid in extending the selections of biocompatible materials and pave the way for the translational use of 3D printing.

Antifouling and Mechanical Properties of Photografted Zwitterionic Hydrogel Thin-Film Coatings Depend on the Cross-Link Density.

Zwitterionic polymer networks have shown promise in reducing the short- and long-term inflammatory foreign body response to implanted biomaterials by combining the antifouling properties of zwitterionic polymers with the mechanical stability provided by cross-linking. Cross-link density directly modulates mechanical properties (i.e., swelling behavior, resistance to stress and strain, and lubricity) but theoretically could reduce desirable biological properties (i.e., antifouling) of zwitterionic materials. This work examined the effect of varying poly(ethylene glycol) dimethacrylate cross-linker concentration on protein adsorption, cell adhesion, equilibrium swelling, compressive modulus, and lubricity of zwitterionic thin films. Furthermore, this work aimed to determine the appropriate balance among each of these mechanical and biologic properties to produce thin films that are strong, durable, and lubricious, yet also able to resist biofouling. The results demonstrated nearly a 20-fold reduction in fibrinogen adsorption on zwitterionic thin films photografted on polydimethylsiloxane (PDMS) across a wide range of cross-link densities. Interestingly, either at high or low cross-link densities, increased levels of protein adsorption were observed. In addition to fibrinogen, macrophage and fibroblast cell adhesion was reduced significantly on zwitterionic thin films, with a large range of cross-link densities, resulting in low cell counts. The macrophage count was reduced by 30-fold, while the fibroblast count was reduced nearly 10-fold on grafted zwitterionic films relative to uncoated films. Increasing degrees of cell adhesion were noted as the cross-linker concentration exceeded 50%. As expected, increased cross-link density resulted in a reduced swelling but greater compressive modulus. Notably, the coefficient of friction was dramatically reduced for zwitterionic thin films compared to uncoated PDMS across a broad range of cross-link densities, an attractive property for insertional implants. This work identified a broad range of cross-link densities that provide desirable antifouling effects while also maintaining the mechanical functionality of the thin films.

Zwitterionic Photografted Coatings of Cochlear Implant Biomaterials Reduce Friction and Insertion Forces.

HYPOTHESIS: Application of photografted zwitterionic coatings to cochlear implant (CI) biomaterials will reduce friction and insertion forces. BACKGROUND: Strategies to minimize intracochlear trauma during implantation of an electrode array are critical to optimize outcomes including preservation of residual hearing. To this end, advances in thin-film zwitterionic hydrogel coatings on relevant biomaterials may show promise, in addition to the potential of these materials for decreasing the intracochlear foreign body response. METHODS: Using a recently designed one-step process, thin-film coatings derived from zwitterionic sulfobetaine methacrylate (SBMA) were photopolymerized and photografted to the surface of polydimethylsiloxane (PDMS, silastic) samples and also to CI arrays from two manufacturers. Fluorescein staining and scanning electron microscopy with energy-dispersive X-ray spectroscopy verified and characterized the coatings. Tribometry was used to measure the coefficient of friction between uncoated and coated PDMS and synthetic and biological tissues. Force transducer measurements were obtained during insertion of uncoated (n = 9) and coated (n = 9) CI electrode arrays into human cadaveric cochleae. RESULTS: SBMA thin-film coating of PDMS resulted in >90% reduction in frictional coefficients with steel, ceramic, and dermal tissue from guinea pigs (p < 0.0001). We employed a novel method for applying covalently bonded, durable, and uniform coating in geographically selective areas at the electrode array portion of the implant. Image analysis confirmed uniform coating of PDMS systems and the CI electrode arrays with SBMA polymer films. During insertion of electrode arrays into human cadaveric cochleae, SBMA coatings reduced maximum force by ∼40% during insertion (p < 0.001), as well as decreasing force variability and the overall work of insertion. CONCLUSION: Thin-film SBMA photografted coatings on PDMS and electrode arrays significantly reduce frictional coefficients and insertional forces in cadaveric cochleae. These encouraging findings support that thin-film zwitterionic coating of CI electrode arrays may potentially reduce insertional trauma and thereby promote improved hearing and other long-term outcomes.