Sterilization effects on ultrathin film polymer coatings for silicon-based implantable medical devices

Biomaterials, 2009

Immobilization of defined chemical functionalities to biomaterial surfaces is employed to optimize them not only for tissue compatibility but also for prevention of bacterial infection. Grafting surfaces with chains of poly(ethylene glycol) (PEG) results in bacterial repellence whereas modification with cationic groups conveys them with bactericidal properties. Since biomaterials in situ will become exposed to a protein-rich environment, it is necessary to investigate the influence of prior protein adsorption on the antibacterial activity of this type of chemical surface modification. In the present study, we immobilized short-chain PEG and two pyridinium group-containing methacrylate monomers, 12-methacryloyloxydodecylpyridinium bromide (MDPB) and 6-methacryloyloxyhexylpyridinium chloride (MHPC), to silicon wafer model surfaces to investigate the influence of prior protein adsorption on the bactericidal activity of the surface coating towards subsequently attached bacteria. Adsorbed amounts of human serum albumin and salivary proteins were found to be two times higher on cationic compared to PEG-modified surfaces. An analogous tendency was found for attachment of Streptococcus gordonii and Streptococcus mutans to the same surfaces without prior protein exposure. However, most bacteria attached to cationic surfaces were found to be dead. Prior exposure of cationic surfaces to protein solutions drastically altered bacterial attachment dependent on the type of protein solution and bacterial species employed. Significantly, the original bactericidal activity of pyridinium-coated surfaces was found greatly reduced upon adsorption of a protein film. As a conclusion we propose that future approaches should combine the protein-and bacteria-repellent properties of PEG-coatings with the bactericidal function of charged cationic groups.

ACS Nano, 2008

MRS Proceedings, 2004

ABSTRACTThe initial response of blood exposed to an artificial surface is the adsorption of blood proteins that triggers a number of biological reactions such as inflammation and blood coagulation. Competitive protein adsorption plays a key role in the hemocompatibility of the surface. The synthesis of nonfouling surfaces is therefore one of the major prerequisites for devices for biomedical applications. Polysaccharides are the main components of the endothelial cell glycocalyx and have the ability to reduce nonspecific protein adsorption and cell adhesion and, therefore, are generally coupled with a wide variety of surfaces to improve their biocompatibility. We have developed a procedure for covalently binding dextran and sodium hyaluronate (HA) on silicon wafers and we have been able to achieve a high level of control over the surface properties of the coatings. In the present research effort we focus on a detailed investigation of competitive bovine serum albumin (BSA) and bovin...

Journal of Biomedical Materials Research Part A, 2008

Silicon wafers modified by silanisation with different functional groups are used to study the bioactivity of surfaces with varying physicochemical properties. Oxidation of the wafers created very hydrophilic surfaces, and moderately wettable surfaces were produced by coating with poly(ethylene glycol) (PEG). Immobilization of hydrocarbon chains to the wafers produced hydrophobic surfaces, and hydrophobicity was further increased by fluorocarbon coatings. The oxidized and the hydrocarbon-modified surfaces supported the adhesion of human MG-63 osteoblasts and 3T3 mouse fibroblasts as well as Staphylococcus aureus 8325-4. Adhesion of osteoblasts and fibroblasts, however, was decreased on highly hydrophobic fluorocarbon surfaces, whereas adhesion of S. aureus was supported. Coating of the fluorocarbon surface with fibronectin increased the number of attached eukaryotic cells, but the accumulation of bacteria remained unchanged. In contrast, surface coatings with PEG-groups inhibited the binding of S. aureus; however, the adhesion of the eukaryotic cells was high. The number of S. aureus on PEG-modified surfaces covered with fibronectin increased about twofold, yet it was still decreased to 25-30% related to the number of bacteria on other surfaces. These findings provide evidence that the PEG-modified surfaces showed selective bioactivity, preventing the attachment of a microbial pathogen but supporting the adhesion of eukaryotic cells.

Annals of Biomedical Engineering, 2011

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/ or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories-coagulation (thrombin-antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems.

Colloids and Surfaces B: Biointerfaces, 2006

Shunt infections are one of the most serious complications in shunt implant surgery. Previous studies have suggested that cerebrospinal fluid (CSF) proteins could affect bacterial adhesion and subsequent shunt infection. A systematic study using immobilized protein on the surface of silane-modified silicone was conducted to determine how these modifications influenced Staphylococcus epidermidis adhesion and colonization. A comparison was also made with silicone having physically adsorbed protein. A colony-counting adhesion assay and scanning electron microscopy (SEM) were used to provide quantitative analysis of bacterial adhesion and semi-quantitative analysis of bacterial colonization, respectively. In order to determine the appropriate silanization process for effective protein immobilization, the effect of bovine serum albumin (BSA) immobilized on n-3-(trimethoxysilyl)propyl-ethylenediamine (AEAPS)/silicone, aminopropyltriethoxysilane (APTMS)/silicone, 3-(glycidyloxypropyl)trimethoxysilane (GPTMS)/silicone, and octadecyltrichlorosilane (OTS)/silicone on bacterial adhesion was investigated. Upon identifying that OTS is the most effective silane, different types of proteins, including: BSA, human serum albumin (HSA), ␥-globulin, and fibrinogen were immobilized on OTS/silicone by a photo-immobilization method. Immobilized protein on modified silicone surfaces was found to be stable in saline for 30 days, while physically adsorbed protein showed instability within hours as determined by contact angle measurements and X-ray photoelectron spectroscopy (XPS). For HSA/OTS/silicone, BSA/OTS/silicone, ␥-globulin/OTS/silicone, fibrinogen/OTS/silicon, and physically absorbed BSA on silicone, the contact angles were 78.5 • , 80.7 • , 78.9 • , 81.3 • , and 96.5 • ; and the amount of nitrogen content was found to be 4.6%, 5.0%, 5.6%, 7.2%, and 3.2%, respectively. All protein immobilized on OTS/silicone surfaces significantly reduced bacterial adhesion by around 75% compared to untreated silicone, while physically adsorbed BSA on silicone reduced by only 29.4%, as determined by colonycounting adhesion assay. However, there was no significant difference on bacterial adhesion among the different types of proteins immobilized on OTS/silicone. Minimizing bacterial adhesion and colonization can be attributed to the increased concentration of -NH 2 group, and stability and more hydrophilic nature of the protein/OTS/silicone surfaces.

The modification of silicon oxide with poly(ethylene glycol) to effectively eliminate protein adsorption has proven to be technically challenging. In this paper, we demonstrate that surface-initiated atom transfer radical polymerization (SI-ATRP) of oligo(ethylene glycol) methyl methacrylate (OEGMA) successfully produces polymer coatings on silicon oxide that have excellent protein resistance in a biological milieu. The level of serum adsorption on these coatings is below the detection limit of ellipsometry. We also demonstrate a new soft lithography method via which SI-ATRP is integrated with microcontact printing to create micropatterns of poly(OEGMA) on glass that can spatially direct the adsorption of proteins on the bare regions of the substrate. This ensemble of methods will be useful in screening biological interactions where nonspecific binding must be suppressed to discern low probability binding events from a complex mixture and to pattern anchorage-dependent cells on glass and silicon oxide.

Biomaterials, 2005

Polydimethylsiloxane elastomers were surface modified with passivating polyethylene oxide (PEO) polymers of different molecular weights, both monofunctional and bifunctional. Following the introduction of Si-H groups on the surfaces by acidcatalyzed equilibration in the presence of polymethylhydrosiloxane, the PEO was linked by platinum-catalyzed hydrosilylation. ATR-FTIR, X-ray photoelectron spectroscopy (XPS) and water contact angle results confirmed that the PEO was successfully grafted to the silicone rubber. Atomic force microscopy and XPS suggested that surface coverage with PEO was very high on the modified surfaces but not complete. The protein-resistant properties of the PEO-modified surfaces were demonstrated by measuring the adsorption of fibrinogen from both buffer and plasma. Fibrinogen adsorption from buffer to the PEO-modified surfaces was reduced by more than 90% compared with controls. r (M.A. Brook), sheardow@mcmaster.ca (H. Sheardown).

Procedia Engineering, 2011

X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM) and Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS) were applied to characterize two series of silicon nitride surfaces, modified either with (3aminopropyl)triethoxysilane (APTES) or (3-glycidoxypropyl)trimethoxysilane (GOPS), prior to and after immobilization of rabbit gamma globulins (rIgG) at different concentrations and blocking with bovine serum albumin (BSA). Higher rIgG amount was adsorbed to surfaces silanized with APTES rather than GOPS, resulting in different behavior to subsequent blocking. There was no increase in total protein surface density due to blocking with BSA for surfaces with already high protein coverage. Apparently, BSA molecules were partly exchanged with rIgG ones, in case of APTES and higher rIgG concentrations, or attached to free surface sites, for GOPS modified surfaces.

Macromolecular Materials and Engineering, 2016

The effects of ethylene oxide (EO), vaporized hydrogen peroxide (VHP), gamma (γ) radiation, and electron-beam (E-beam) on the physiochemical and morphological properties of medical