Tailoring Cell Response on Electroactive Piezoelectric Materials Though Surface Protein Deposition and Morphology

The physical-chemical properties of scaffolds used for tissue regeneration strategies have a direct impact on cell shape, adhesion, proliferation, phenotypic and differentiation. Thus, biophysical and biochemical cues have been widely used to design and develop biomaterial systems for specific tissue engineering strategies.<br/>Further, the protein-material interface is driven by the physical-chemical interactions that occur when proteins come into contact with the surface. These interactions are facilitated by the properties of the biomaterial, including wettability, stiffness, topography and chemical composition, and determine the biological effect of the biomaterial on the cells adhering to it. However, a significant limitation for the design and modification of materials to improve their biological activity lies in the insufficient understanding of the mechanisms that govern the formation of the protein interface.<br/>This is particularly relevant in the case of electroactive materials, increasingly used for the development of active microenvironments for tissue regeneration. Poly(vinylidene fluoride) (PVDF) is a piezoelectric polymer known for its high biocompatibility and non-biodegradability [1]. PVDF has been consequently used for static cultures and in dynamic setups in which a variation of the surface charge provides cells with a cyclic electrical stimulus, showing its potential for bone, muscle, and neural tissues regeneration [1].<br/>In this context, we have explored the interaction of collagen type-I, the most abundant mammalian extracellular protein, with polyvinylidene fluoride (PVDF), revealing significant differences in collagen affinity, conformation, and interaction strength depending on the electric charge of the PVDF surface, which subsequently affects the behaviour of mesenchymal stem cells seeded on them. These findings highlight the importance of surface charge in the establishment of the material-protein interface and ultimately in the biological response to the material.<br/>Moreover, the specific surface morphology of those piezoelectric polymers allows to further guide cell response, by taking into consideration both final functional cell shape and electroactivity. It is shown how patterned anisotropic electroactive scaffolds allow to promote muscle differentiation, whereas isotropic ones are more suitable for osteoblast differentiation. Those effects are reinforced by biochemical stimuli. However, when the physical stimulus is not adequate to the tissue, e.g. isotropic microstructure, the biochemical stimulus has the opposite effect, the differentiation process is hindered. Therefore, the proper morphological design of the electroactive scaffold combined with dynamic electroactive and biochemical stimulus allows to enhance cell differentiation and allows the development of advanced strategies for effective tissue engineering of electroactive tissues.<br/><br/><b>Acknowledgments</b><br/>Advanced Materials program, supported by MCIN with funding from European Union NextGenerationEU (PRTR-C17.I1) as well as by IKUR Strategy. Department of Education of the Basque Government (PIBA program, Grant number 2022333047) and by the Spanish Ministry of Science and Innovation (Grant number PID2022-138572OB-C42).<br/><br/>[1] Costa CM, Cardoso VF, Martins P, Correia DM, Gonçalves R, Costa P, et al. Smart and Multifunctional Materials Based on Electroactive Poly(vinylidene fluoride): Recent Advances and Opportunities in Sensors, Actuators, Energy, Environmental, and Biomedical Applications. Chemical Reviews. 2023;123:11392-487.