Soft hydrogel zwitterionic coatings minimize fibroblast and macrophage adhesion on polyimide substrates

Minimizing the foreign body reaction to polyimide-based implanted devices has a pivotal role for several biomedical applications. In this work we propose materials exhibiting non-biofouling properties and a Young's modulus reflecting the one of soft human tissues. We describe the synthesis, characterization and in vitro validation of poly(carboxybetaine) hydrogel coatings covalently attached to polyimide substrates via a photolabile 4-azidophenyl group, incorporated in poly(carboxybetaine) chains at two concentrations of 1.6 and 3.1 mol.%. The presence of coatings was confirmed by attenuated total reflectance Fourier-transform infrared spectroscopy. White light interferometry was used to evaluate coating continuity and thickness (resulting between 3 and 6 μm in dry conditions). Confocal laser scanning microscopy allowed to quantify the thickness of the swollen hydrogel coatings that ranged between 13 and 32 μm. The different hydrogel formulations resulted in stiffness values ranging from 2 to 19 kPa, and led to different fibroblasts and macrophages responses tested in vitro. Both cell types showed a minimum adhesion on the softest hydrogel type. In addition, both the overall macrophage activation and cytotoxicity were observed to be negligible for all the tested material formulations. These results are a promising starting point towards future advanced implantable systems. In particular, such technology paves the way to novel neural interfaces able to minimize the fibrotic reaction, once implanted in vivo, and to maximize their long-term stability and functionality.