The role of surface zeta potential and substratum chemistry for regulation of dermal fibroblasts interaction

Synthetic materials considered for biohybrid skin or other tissue engineering applications have to support cellular interaction and colonisation of implants. However, despite the number of studies reported in the literature, there is no agreement on the principal factors applicable to modulate the interaction with cells, such as the wettability of biomaterials, their surface potential and chemistry of the surface. Particularly, in this study we were interested on the impact of surface chemistry and net surface (zeta) potential on dermal fibroblasts. To address this question self assembled monolayers of silanes on glass, further derivatized with different functional groups, were used to study the adhesion and proliferation of human skin fibroblasts in response to these factors. The model surfaces were characterized using streaming potential (zeta potential) and water contact angle measurements. All samples were found to be negatively charged at physiological pH (regardless of the different chemistry) increasing (or equal similar to) the magnitude of the negative potential in the following order: hydroxy (OH) < arnine (NH2) similar to epoxy (EPOXY) < carboxyl (COOH) < three-fluorocarbon (CF3) < sulfonic (SO3) functionalities. The interaction of fibroblast characterized by the effectiveness of cell adhesion, spreading and actin stress fibres formation decreased almost in the opposite order: NH2 > OH > EPOXY > SO3 > COOH > CF3 functions.-The surfaces were found also to be highly wettable, except CF3. Interestingly, the best cellular interaction was found on the moderately wettable NH2 surface representing water contact angle (CA) of 65degrees, and the worst, on the least wettable CF3 surface (CA 85degrees) indicating that not only the surface potential but also the type of functional groups may play an important role. The organisation of alpha5 and beta3 integrins generally followed the same trend of less clustering in focal adhesion plaques when the negative potential increased, except on SO3 surface, where beta3 but not alpha5 integrins were greatly expressed. Cell growth however, showed a significant decrease on highly charged COOH and SO3 surfaces, as well as, on non-polar CF3 functions. The best proliferation response was obtained on surfaces with primary amine groups. The results indicate that the surface (zeta) potential might be a critical parameter for cellular interactions, but also the substratum wettability and the type of functional groups have to be controlled in order to improve the biocompatibility of material surfaces.