Application of nanobiomaterials for biofouling attenuation

The research described here investigates the hypothesis that surface nanoarchitecture is capable of attenuating the adverse host response generated when medical devices are implanted in the body. This adverse host response, or biofouling, generates an avascular fibrous mass transfer barrier between the device and extracellular environment, disabling the implant if it is a sensor. Numerous studies have indicated that surface chemistry and architecture modulate the host response. These findings led me to hypothesize that nanostructured surfaces will significantly inhibit the formation of an avascular fibrous capsule. We are investigating whether arrays of oscillating magnetostrictive nanowires, a nanostructured PTFE (nPTFE) surface, or a hyperbranched poly(ethylene glycol) (PEG) and poly(allylamine) (PAAM) surface can prevent protein adsorption and cell adhesion. Magnetostrictive nanowires were fabricated by electroplating a ferromagnetic metal alloy into the pores of a nanoporous alumina template. Nanostructured PTFE coatings were created by jet-blowing PTFE onto glass surfaces. Hyperbranched surfaces were created by alternating layers of PAAM and PEG on silicon. Protein adsorption results displayed a reduced amount of protein per surface area of static nanowires, significant at an initial concentration of 1 mg/mL bovine serum albumin (BSA). This attenuation of protein adsorption was increased by vibrating the nanowires. Reduced protein adsorption was linked to the increased hydrophilicity of the static wires and shear-linked detachment of proteins on vibrating nanowires. Albumin adsorption on the nPTFE surface was slightly higher than that found in literature. The hyperbranched polymer surface showed an attenuation of protein adsorption with both the PEG and PRAM surfaces. The PEG has a much higher rejection rate of protein compared to the PRAM surface; however both surfaces adsorbed less protein than silicon. An additional study addressed cell adhesion, in particular, macrophage, fibroblast and endothelial cell adhesion. We found that the cells on the nanowires and nPTFE typically occupy less area and are more circular than on a flat surface of the same material (control wafers) or tissue culture polystyrene (TCPS), respectively. Furthermore, this difference is amplified by pre-coating the nanostructured surfaces with collagen. This circular, non-spread shape has been linked to non-thriving cells and indeed the dead cell to live cell ratio of fibroblasts on the surfaces was significantly higher compared to the ratio tissue on the respective control. Since there is a high amount of cell death, and the process of biofouling is a chronic inflammation, an eighteen cytokine LuminexRTM panel was performed on the supernatant from the surface. The results conclude that the nanowires are immunogenic whereas the nPTFE surface was not. Overall, the thesis shows that nanoarchitecture can disrupt adsorption of protein. And by disrupting the protein adsorption on the surface, cell adhesion is significantly altered also. These results indicate that a nanostructured surface could significantly reduce the biofouling response in vivo. Further studies would need to be characterized to conclude the viability of such an implant surface.