Engineering Regeneration Through Light: Modular Biomaterial Platforms for 3D Biofabrication

N. Pien¹, L. Parmentier¹, J. Van Meerssche¹, N. Deroose¹, B. Bogaert¹, M. Meeremans^1,2, I. Pokholenko^1,2, Q. Thijssen¹, A. Jaén-Ortega¹, F. Bray³, K. Dixit⁴, N. Eeckman⁵, A. Shajahan⁶, C. Rolando³, D. Mantovani⁷, S. Miettinen⁴, S. Porsborg⁶, P. Dubruel¹, P. Pennisi⁶, C. De Schauwer², S. Van Vlierberghe¹

¹ Polymer Chemistry and Biomaterials Group, Centre of Macromolecular Chemistry, Ghent University, Belgium

² Veterinary Stem Cell Research Unit, Ghent University, Belgium

³ Miniaturisation pour la Synthèse l'Analyse et la Protéomique (MSAP), Université de Lille, France

⁴ Tampere University, Tampere, Finland

⁵ 4Tissue, Zwijnaarde, Belgium

⁶ Aalborg Universitet, Gistrup, Denmark

⁷ Laboratory for Biomaterials and Bioengineering, Laval University, Canada

Tissue engineering and regenerative medicine increasingly rely on the integration of advanced biomaterial design with innovative processing technologies. Biomaterials provide biochemical, mechanical and degradation-related cues that guide cell behaviour, while 3D printing enables their organisation into defined three-dimensional architectures. Combining material chemistry with engineering-driven fabrication is therefore essential to move towards more biomimetic tissue models and regenerative constructs.

Two complementary material platforms are explored. The first is based on natural gelatin-derived hydrogels, which offer intrinsic cell-interactive motifs, enzymatic degradability and broad chemical versatility. Through functionalisation into gelatin-methacryloyl, gelatin-norbornene/thiolated gelatin thiol-ene systems and bifunctional methacryloyl-norbornene gelatin, a modular toolbox can be created with tuneable crosslinking mechanisms, stiffness, swelling and cell-encapsulation potential. Proteomics-based mapping and 3D modelling further support structure-function understanding in modified gelatin networks.[1] The second platform consists of synthetic light-processable polymer networks, including acrylate-endcapped urethane-based precursors and thiol-ene systems, designed to expand the accessible mechanical and processing window for biomedical 3D printing.

These materials are processed using two light-based 3D printing platforms. Digital light processing enables layer-by-layer fabrication of high-resolution constructs. Gelatin-based formulations are being developed for cell-compatible DLP biofabrication, while synthetic acrylate-endcapped urethane-based precursors have been processed into mechanically tuneable constructs for biomedical applications, including cartilage-oriented designs, and tubular structures relevant for vascular tissue models.[2,3] Volumetric additive manufacturing, in contrast, enables rapid fabrication of complex centimetre³-scale structures within seconds. Gelatin-based bioinks support homogeneous mesenchymal stromal cell encapsulation and post-printing cell behaviour studies.[4] Ongoing GelMANB work expands this platform towards programmable crosslinking strategies, while synthetic biodegradable and recyclable thiol-ene photoresists highlight the broader potential of VAM for complex biomedical structures.[5]

References. 

[1] Parmentier L, Bray F, Van Meerssche J, Gheysens T, Wynendaele E, Rolando C, Van Vlierberghe S, Pien N. Structure-function relationship of methacryloyl-modified gelatin revealed by proteomics and 3D modeling. Applied Materials Today. 2026;48:103072. doi:10.1016/j.apmt.2025.103072. 

[2] Pien N, Deroose N, Meeremans M, Perneel C, Popovici C-S, Dubruel P, De Schauwer C, Van Vlierberghe S. Tailorable acrylate-endcapped urethane-based polymers for precision in digital light processing: Versatile solutions for biomedical applications. Biomaterials Advances. 2024;162:213923. doi:10.1016/j.bioadv.2024.213923. 

[3] Pien N, Pokholenko I, Deroose N, Perneel C, Vinturelle R, Meeremans M, Mantovani D, Van Vlierberghe S, De Schauwer C. Toward in vitro vascular wall models: Digital light processing of acrylate-endcapped urethane-based polymers into tubular constructs. Macromolecular Chemistry and Physics. 2024;225:2400277. doi:10.1002/macp.202400277.

[4] Pien N, Bogaert B, Meeremans M, Popovici C-S, Dubruel P, De Schauwer C, Van Vlierberghe S. Exploring the impact of volumetric additive manufacturing of photo-crosslinkable gelatin on mesenchymal stromal cell behavior and differentiation. Additive Manufacturing. 2025;109:104850. doi:10.1016/j.addma.2025.104850. 

[5] Thijssen Q, Jaen-Ortega A, Pien N, Van Vlierberghe S. Volumetric 3D printing of a fluoropolymer and closed-loop chemical recycling of its fluorinated content. Nature Communications. 2026;17:4153. doi:10.1038/s41467-026-70897-z.

Acknowledgements. 

N. Pien would like to acknowledge Horizon Europe for funding the STRONG-UR project (Grant agreement ID: 101191695). STRONG-UR is a project funded by the European Union and has received funding from the Horizon Europe programme under grant agreement No 101191695. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or HaDEA. Neither the European Union nor the granting authority can be held responsible for them.