Inhibition of fibroblast adhesion by covalently immobilized protein repellent polymer coatings studied by single cell force spectroscopy

Abstract

Cochlea implants (CI) restore the hearing in patients with sensorineural hearing loss by electrical stimulation of the auditory nerve via an electrode array. The increase of the impedance at the electrode-tissue interface due to a postoperative connective tissue encapsulation leads to higher power consumption of the implants. Therefore, reduced adhesion and proliferation of connective tissue cells around the CI electrode array is of great clinical interest. The adhesion of cells to substrate surfaces is mediated by extracellular matrix (ECM) proteins. Protein repellent polymers (PRP) are able to inhibit unspecific protein adsorption. Thus, a reduction of cell adhesion might be achieved by coating the electrode carriers with PRPs. The aim of this study was to investigate the effects of two different PRPs, poly(dimethylacrylamide) (PDMAA) and poly(2-ethyloxazoline) (PEtOx), on the strength and the temporal dynamics of the initial adhesion of fibroblasts. Polymers were immobilized onto glass plates by a photochemical grafting onto method. Water contact angle measurements proved hydrophilic surface properties of both PDMAA and PEtOx (45 ± 1° and 44 ± 1°, respectively). The adhesion strength of NIH3T3 fibroblasts after 5, 30, and 180 s of interaction with surfaces was investigated by using single cell force spectroscopy. In comparison to glass surfaces, both polymers reduced the adhesion of fibroblasts significantly at all different interaction times and lower dynamic rates of adhesion were observed. Thus, both PDMAA and PEtOx represented antiadhesive properties and can be used as implant coatings to reduce the unspecific ECM-mediated adhesion of fibroblasts to surfaces.

Wafer‐Scale Fabrication of Conducting Polymer Hydrogels for Microelectrodes and Flexible Bioelectronics

“…In the ISO guidelines ( ISO 10 993–5:2009 Biological evaluation of medical devices: Tests for in vitro cytotoxicity ), it is, for example, recommended that cytotoxic effects may be considered when the cell viability is reduced by more than 30%. Rather we suggest that this is an effect of the antibiofouling properties which previously have been explored for PDMAAp systems, which would reduce protein adsorption to the surface and thereby provide fewer adhesion sites for the seeded cells . This would in turn influence cell spreading on and in addition increase the likelihood that the washing procedure detached of some cells before imaging.…”

Biocompatibility of poly(2-alkyl-2-oxazoline) brush surfaces for adherent lung cell lines

“…However, in view of the marked differences in the structural properties of bacterial cell walls and mammalian cell membranes, it is not unreasonable to expect differences in binding. Another conflicting study reported that fibroblast adhesion was reduced when commercially available, high molar mass PEtOx was immobilized onto glass plates by photochemical grafting [29]. However, in this case, adhesion was measured using single cell force microscopy over a period of up to just 180 seconds.…”

A silicone fiber coating as approach for the reduction of fibroblast growth on implant electrodes

“…A modification of the electrode array that sustainingly reduces the increase in electrode impedance after implantation would not only improve quality of current CIs, it would be an important prerequisite for the development of implants with higher electrode numbers and necessarily smaller electrode areas. Various attempts to counteract fibrosis formation have been successfully demonstrated such as steroid administration during surgery, modification of the surgical electrode entry to the cochlea, incorporation of materials promoting drug release or various coatings of the electrodes . So far, a decrease in electrode impedance over years was only shown for the relatively uncontrolled intraoperative administration of steroids, while nano‐structuring of the platinum contact surface only resulted in a delayed increase in impedance …”

“…Various attempts to counteract fibrosis formation have been successfully demonstrated such as steroid administration during surgery, 7,8 modification of the surgical electrode entry to the cochlea, 9 incorporation of materials promoting drug release [10][11][12][13] or various coatings of the electrodes. 14,15 So far, a decrease in electrode impedance over years was only shown for the relatively uncontrolled intraoperative administration of steroids, 16 while nano-structuring of the platinum contact surface only resulted in a delayed increase in impedance. 17 Here, we investigate the application of a silicone fiber coating that itself does not increase electrode impedance but inhibits fibroblast growth.…”