Increasing the Microfabrication Performance of Synthetic Hydrogel Precursors through Molecular Design

• Published in: Biomacromolecules 2021-12, Vol.22 (12), p.4919-4932
• Main Authors: Arslan, Aysu, Vanmol, Koen, Dobos, Agnes, Natale, Alessandra, Van Hoorick, Jasper, Roose, Patrice, Van den Bergen, Hugues, Chalyan, Tatevik, Ovsianikov, Aleksandr, Baudis, Stefan, Rogiers, Vera, Vanhaecke, Tamara, Rodrigues, Robim M, Thienpont, Hugo, Van Erps, Jürgen, Van Vlierberghe, Sandra, Dubruel, Peter
• Format: Article
• Language: English
• Subjects: Equipment Design - methods; Gelatin - chemistry; Hydrogels - chemistry; Manufacturing Industry; Microtechnology; Polymerization; Tissue Engineering - methods
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.1c00704

Implementation of hydrogel precursors in two-photon polymerization (2PP) technology provides promising opportunities in the tissue engineering field thanks to their soft characteristics and similarity to extracellular matrix. Most of the hydrogels, however, are prone to post-fabrication deformations, leading to a mismatch between the computer-aided design and the printed structure. In the present work, we have developed novel synthetic hydrogel precursors to overcome the limitations associated with 2PP processing of conventional hydrogel precursors such as post-processing deformations and a narrow processing window. The precursors are based on a poly­(ethylene glycol) backbone containing urethane linkers and are, on average, functionalized with six acrylate terminal groups (three on each terminal group). As a benchmark material, we exploited a precursor with an identical backbone and urethane linkers, albeit functionalized with two acrylate groups, that were reported as state-of-the-art. An in-depth characterization of the hexafunctional precursors revealed a reduced swelling ratio (36 MPa Young’s modulus) compared to their difunctional analogs. The superior physical properties of the newly developed hydrogels lead to 2PP-based fabrication of stable microstructures with excellent shape fidelity at laser scanning speeds up to at least 90 mm s–1, in contrast with the distorted structures of conventional difunctional precursors. The hydrogel films and microscaffolds revealed a good cell interactivity after functionalization of their surface with a gelatin methacrylamide-based coating. The proposed synthesis strategy provides a one-pot and scalable synthesis of hydrogel building blocks that can overcome the current limitations associated with 2PP fabrication of hydrogel microstructures.