RESUMEN
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.
Asunto(s)
Materiales Biocompatibles Revestidos , Implantes Cocleares , Hidrogeles , Ensayo de Materiales , Hidrogeles/química , Humanos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Propiedades de Superficie , Tamaño de la PartículaRESUMEN
The foreign body response to implanted materials often complicates the functionality of sensitive biomedical devices. For cochlear implants, this response can reduce device performance, battery life and preservation of residual acoustic hearing. As a permanent and passive solution to the foreign body response, this work investigates ultra-low-fouling poly(carboxybetaine methacrylate) (pCBMA) thin film hydrogels that are simultaneously photo-grafted and photo-polymerized onto polydimethylsiloxane (PDMS). The cellular anti-fouling properties of these coatings are robustly maintained even after six-months subcutaneous incubation and over a broad range of cross-linker compositions. On pCBMA-coated PDMS sheets implanted subcutaneously, capsule thickness and inflammation are reduced significantly in comparison to uncoated PDMS or coatings of polymerized poly(ethylene glycol dimethacrylate) (pPEGDMA). Further, capsule thickness is reduced over a wide range of pCBMA cross-linker compositions. On cochlear implant electrode arrays implanted subcutaneously for one year, the coating bridges over the exposed platinum electrodes and dramatically reduces the capsule thickness over the entire implant. Coated cochlear implant electrode arrays could therefore lead to persistent improved performance and reduced risk of residual hearing loss. More generally, the in vivo anti-fibrotic properties of pCBMA coatings also demonstrate potential to mitigate the fibrotic response on a variety of sensing/stimulating implants. STATEMENT OF SIGNIFICANCE: This article presents, for the first time, evidence of the in vivo anti-fibrotic effect of zwitterionic hydrogel thin films photografted to polydimethylsiloxane (PDMS) and human cochlear implant arrays. The hydrogel coating shows no evidence of degradation or loss of function after long-term implantation. The coating process enables full coverage of the electrode array. The coating reduces fibrotic capsule thickness 50-70% over a broad range of cross-link densities for implantations from six weeks to one year.
Asunto(s)
Implantes Cocleares , Cuerpos Extraños , Humanos , Hidrogeles/farmacología , Hidrogeles/metabolismo , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/metabolismo , DimetilpolisiloxanosRESUMEN
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.
Asunto(s)
Incrustaciones Biológicas , Hidrogeles , Adsorción , Materiales Biocompatibles , Incrustaciones Biológicas/prevención & control , PolímerosRESUMEN
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 (nâ=â9) and coated (nâ=â9) 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 (pâ<â0.0001). 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 â¼40% during insertion (pâ<â0.001), 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.
Asunto(s)
Implantación Coclear , Implantes Cocleares , Animales , Materiales Biocompatibles , Cóclea/cirugía , Implantación Coclear/métodos , Fricción , CobayasRESUMEN
Due to its attractive mechanical properties and biocompatibility, poly(dimethyl)siloxane (PDMS) is widely used in the fabrication of biomedical materials. On the other hand, PDMS is also prone to adsorption of both proteins and bacteria, making PDMS implants susceptible to infection. Herein, we examine the use of durably cross-linked zwitterionic coatings for PDMS surfaces to mitigate bacterial adhesion. Using a single-step photografting technique, poly(sulfobetaine methacrylate) (pSBMA) and poly(carboxybetaine methacrylate) (pCBMA) thin films were covalently attached to PDMS substrates. The abilities of these coatings to resist the adhesion of Staphylococcus aureus and Staphylococcus epidermidis were tested in vitro under both wet and droplet conditions, as well as in subcutaneous and transcutaneous implantation models using Sprague-Dawley rats. Zwitterionic thin films effectively reduced bacterial adhesion in both in vitro and in vivo conditions. This was particularly true for pCBMA-coated materials, which exhibited significant reduction in bacterial adhesion and growth with respect to S. aureus and S. epidermidis for all in vitro conditions as well as the ability to resist bacterial growth on PDMS implants. The results of this study suggest that a simple and durable photografting process can be used to produce polymer thin films capable of preventing infection of implantable medical devices.
Asunto(s)
Adhesión Bacteriana , Dimetilpolisiloxanos/química , Procesos Fotoquímicos , Staphylococcus aureus/fisiología , Staphylococcus epidermidis/fisiología , Animales , Materiales Biocompatibles , Biopelículas , Incrustaciones Biológicas , Implantes Experimentales , Ratas , Ratas Sprague-Dawley , Propiedades de SuperficieRESUMEN
This study investigated the potential of delivering an anti-glaucoma drug using commercial silicone hydrogel (SiHy) contact lenses. The moderately hydrophobic drug latanoprost was rapidly loaded in 4 min by swelling contact lenses in a solution of the drug in n-propanol. A fraction of the drug was radiolabeled, thus allowing measurement of the uptake and subsequent release of drug into artificial tear fluid. Three questions were addressed: (1) how much drug can be loaded into each type of lens, (2) how fast is drug release, and (3) how are these values related to the contact lens chemistry. The results showed that much more latanoprost could be loaded into SiHy lenses than a conventional contact lens of poly(hydroxyethyl methacrylate). The drug uptake correlated with the amount of swelling in n-propanol, with Galyfilcon lenses having the greatest swelling and highest drug uptake. The drug release from the SiHy lenses occurred over days, whereas the conventional lens released nearly all drug in a burst over a few hours. To examine correlations between lens chemistry, drug chemistry and uptake, and solvent chemistry, the Hansen solubility parameters were calculated using estimates of contact lens chemistry. These results showed that drug uptake in SiHy lenses correlated with favorable solubility parameter interactions between the n-propanol and the lens material, but did not correlate with interactions between the drug and the lens materials.