Incorporation of Cell-Adhesive Proteins in 3d Printed Lipoic Acid-Maleic Acid-Poly(Propylene Glycol)-Based Tough Gel Ink for Cell-Supportive Microenvironment.

In extrusion-based 3D printing, the use of synthetic polymeric hydrogels can facilitate fabrication of cellularized and implanted scaffolds with sufficient mechanical properties to maintain the structural integrity and physical stress within the in vivo conditions. However, synthetic hydrogels face challenges due to their poor properties of cellular adhesion, bioactivity, and bio-functionality. In the past few years, new compositions of hydrogel inks have been designed to address this limitation. We recently developed viscous MPLE hydrogel (poly(maleate-propylene oxide)-lipoate-poly(ethylene oxide)) that shows high-resolution printability, drug-controlled release, excellent mechanical properties with adhesiveness, and biocompatibility. In this study, we demonstrate that the incorporation of cell-adhesive proteins like gelatin and albumin within the viscous tough MPLE gel allows printing of biologically functional 3D scaffolds with rapid cell spreading (within 7 days) and high cell proliferation (at least 2-fold increase) as compared to MPLE gel only. Strikingly, addition of proteins (10% w/v) supports the formation of interconnected cell clusters (∼1.6-fold increase in cell areas after 7-day culture period) and spreading of MC3T3 cells in the printed scaffolds without additional growth factors. In in vivo studies, the protein-loaded scaffolds showed excellent biocompatibility and increased angiogenesis without inflammatory response after 4-week implantation in mice, thus demonstrating the promise to contribute to the diversity of newly printable tough hydrogel inks for tissue engineering. This article is protected by copyright. All rights reserved.