From Sub-Micron Resolution Towards 3D-Printing at the Speed of Light: Pushing the Boundaries to Serve Health

Current thoroughly described biodegradable and cross-linkable polymers mainly rely on acrylate cross-linking. However, despite the swift cross-linking kinetics of acrylates, the concomitant brittleness of the resulting materials limits their applicability. Here, photo-cross-linkable poly(ε-caprolactone) (PCL) networks through orthogonal thiol-ene chemistry are introduced. The step-growth polymerized networks are tunable, predictable by means of the rubber elasticity theory and it is shown that their mechanical properties are significantly improved over their acrylate cross-linked counterparts. Tunability is introduced to the materials, by altering <i>M</i>_c (or the molar mass between cross-links), and its effect on the thermal properties, mechanical strength and degradability of the materials is evaluated. Moreover, excellent volumetric printability is illustrated and the smallest features obtained via volumetric 3D-printing to date are reported, for thiol-ene systems. Finally, by means of in vitro and in vivo characterization of 3D-printed constructs, it is illustrated that the volumetrically 3D-printed materials are biocompatible.<br/>In an attempt to mimic nature’s ability to adhere cells, PCL is often coated with nature-derived polymers or its surface is functionalized with a cell-binding motif. However, said surface modifications are limited to the material’s surface, include multiple steps, and are mediated by harsh conditions. In a second part, we introduce a single-step strategy toward cell-adhesive polymer networks where thiol-ene chemistry serves a dual purpose. First, alkene-functionalized PCL was crosslinked by means of a multifunctional thiol (<i>vide supra</i>). Second, by means of a cysteine coupling site, the cell-binding motif C(-linker-)RGD was covalently bound throughout the PCL networks during crosslinking. Moreover, the influence of various linkers (type and length), between the cysteine coupling site and the cell-binding motif RGD, was investigated and the functionalization was assessed by means of static contact angle measurements and X-ray photoelectron spectroscopy. Finally, successful introduction of cell adhesiveness was illustrated for the networks by seeding fibroblasts onto the functionalized PCL networks.<br/>This combination of mechanical stability, tunability, biocompatibility, no post-processing functionalization required and rapid fabrication by volumetric 3D-printing charts a new path toward bedside manufacturing of biodegradable cell-interactive, patient-specific implants.<br/>In addition to photo-crosslinkable polyesters, also progress in the field of high resolution two-photon polymerization and volumetric additive manufacturing of gelatin-based hydrogels will be addressed. Hence, our material platform can serve both hard and soft tissue engineering applications.<br/><br/>References<br/>Thijssen, et al. <i>Biomacromolecules </i>(2023), 24, 1638-1647<br/>Thijssen, et al. <i>Advanced Materials </i>(2023), 35, 2210136<br/>Thijssen and Van Vlierberghe (2022), Cell-binding motifs (CBMs) functionalized polymers, EP22213201.1