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

Abstract

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

Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering

“…This results in hydrogels with superior mechanical, functional and biocompatible properties compared to pure gelatin hydrogels. Also, gelatin can be combined with synthetic polymers to improve the ink's properties, because usually synthetic polymers lack bioactive properties but have high mechanical characteristics [44]. The gelatin-based hydrogel can be crosslinked with a combination of tannic acid and ferrous sulfate to achieve better extrudable and stable properties for 3D bioprinting [45].…”

Biological applications of lipoic acid-based polymers: an old material with new promise

“…7). 32 In in vivo studies, four weeks after implantation in mice, protein-loaded scaffolds showed great biocompatibility and increased angiogenesis without an inflammatory response, demonstrating the promise as a printable tough hydrogel ink for tissue engineering.…”

“…Consequently, these have been extensively studied in biomedical applications, including protein modification, 25,26 tumor treatment, 27,28 biosensing, 29–31 and tissue scaffold 3D-printing. 32 Most reviews 33,34 have primarily focused on the properties and clinical applications of small-molecule LA, while limited attention is given to the synthesis strategies and biological applications of PLA-based systems. In this work, after fully considering the impact of specific structures on biological performances, we highlight the latest advancements of PLA in polymerization methods and biomedical applications, and the prospects for further development in the future (Scheme 1).…”