Tuning Cell Behavior on 3D Scaffolds Fabricated by Atmospheric Plasma-Assisted Additive Manufacturing

[Image: see text] Three-dimensional (3D) scaffolds with optimum physicochemical properties are able to elicit specific cellular behaviors and guide tissue formation. However, cell–material interactions are limited in scaffolds fabricated by melt extrusion additive manufacturing (ME-AM) of synthetic polymers, and plasma treatment can be used to render the surface of the scaffolds more cell adhesive. In this study, a hybrid AM technology, which combines a ME-AM technique with an atmospheric pressure plasma jet, was employed to fabricate and plasma treat scaffolds in a single process. The organosilane monomer (3-aminopropyl)trimethoxysilane (APTMS) and a mixture of maleic anhydride and vinyltrimethoxysilane (MA-VTMOS) were used for the first time to plasma treat 3D scaffolds. APTMS treatment deposited plasma-polymerized films containing positively charged amine functional groups, while MA-VTMOS introduced negatively charged carboxyl groups on the 3D scaffolds’ surface. Argon plasma activation was used as a control. All plasma treatments increased the surface wettability and protein adsorption to the surface of the scaffolds and improved cell distribution and proliferation. Notably, APTMS-treated scaffolds also allowed cell attachment by electrostatic interactions in the absence of serum. Interestingly, cell attachment and proliferation were not significantly affected by plasma treatment-induced aging. Also, while no significant differences were observed between plasma treatments in terms of gene expression, human mesenchymal stromal cells (hMSCs) could undergo osteogenic differentiation on aged scaffolds. This is probably because osteogenic differentiation is rather dependent on initial cell confluency and surface chemistry might play a secondary role.