High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins

Materials Today Bio

Wanlu Li¹  Khoon S. Lim²  Jos Malda³  Ane Urigoitia Asua⁴  Riccardo Levato⁵  Debby Gawlitta⁵  Tim B.F. Woodfield⁶  Marc Falandt⁷  Yu Shrike Zhang⁷  Mian Wang⁷  Paulina Nuñez Bernal⁸  Laura Blanco Peña⁸ 

[1] Corresponding author. Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, the Netherlands.;Department of Orthopaedics, University Medical Center Utrecht, the Netherlands;Special Dental Care, University Medical Center Utrecht, the Netherlands;Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, University of Otago Christchurch, Christchurch, the Netherlands;Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, the Netherlands;;Department of Oral and Maxillofacial Surgery &Department of Orthopaedics, University Medical Center Utrecht, the Netherlands;Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, USA;

关键词: Biofabrication and bioprinting;    Lithography;    Bioresin;    Hydrogel;    Digital light processing;   

DOI  :  

来源: DOAJ

【 摘 要 】

Biofabrication via light-based 3D printing offers superior resolution and ability to generate free-form architectures, compared to conventional extrusion technologies. While extensive efforts in the design of new hydrogel bioinks lead to major advances in extrusion methods, the accessibility of lithographic bioprinting is still hampered by a limited choice of cell-friendly resins. Herein, we report the development of a novel set of photoresponsive bioresins derived from ichthyic-origin gelatin, designed to print high-resolution hydrogel constructs with embedded convoluted networks of vessel-mimetic channels. Unlike mammalian gelatins, these materials display thermal stability as pre-hydrogel solutions at room temperature, ideal for bioprinting on any easily-accessible lithographic printer. Norbornene- and methacryloyl-modification of the gelatin backbone, combined with a ruthenium-based visible light photoinitiator and new coccine as a cytocompatible photoabsorber, allowed to print structures resolving single-pixel features (∼50 ​μm) with high shape fidelity, even when using low stiffness gels, ideal for cell encapsulation (1–2 ​kPa). Moreover, aqueous two-phase emulsion bioresins allowed to modulate the permeability of the printed hydrogel bulk. Bioprinted mesenchymal stromal cells displayed high functionality over a month of culture, and underwent multi-lineage differentiation while colonizing the bioresin bulk with tissue-specific neo-deposited extracellular matrix. Importantly, printed hydrogels embedding complex channels with perfusable lumen (diameter <200 ​μm) were obtained, replicating anatomical 3D networks with out-of-plane branches (i.e. brain vessels) that cannot otherwise be reproduced by extrusion bioprinting. This versatile bioresin platform opens new avenues for the widespread adoption of lithographic biofabrication, and for bioprinting complex channel-laden constructs with envisioned applications in regenerative medicine and hydrogel-based organ-on-a-chip devices.

【 授权许可】

Unknown