Abstract
A major challenge in three-dimensional (3D) bioprinting is the limited number of bioinks that fulfill the physicochemical requirements of printing while also providing a desirable environment for encapsulated cells. Here, we address this limitation by temporarily stabilizing bioinks with a complementary thermo-reversible gelatin network. This strategy enables the effective printing of biomaterials that would typically not meet printing requirements, with instrument parameters and structural output largely independent of the base biomaterial. This approach is demonstrated across a library of photocrosslinkable bioinks derived from natural and synthetic polymers, including gelatin, hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, heparin, and poly(ethylene glycol). A range of complex and heterogeneous structures are printed, including soft hydrogel constructs supporting the 3D culture of astrocytes. This highly generalizable methodology expands the palette of available bioinks, allowing the biofabrication of constructs optimized to meet the biological requirements of cell culture and tissue engineering.
| Original language | English |
|---|---|
| Article number | eabc5529 |
| Journal | Science Advances |
| Volume | 6 |
| Issue number | 38 |
| DOIs | |
| Publication status | Published - 16 Sept 2020 |
Bibliographical note
Funding Information:We acknowledge L. Li for help with the schematic drawing in Fig. 1, S. C. Skaalure for help with materials preparation, S. Treumuth for help with cell isolation and culture, T. Benge for help with ALP assay, G. Miklosic and A. Moore for help with mechanical data analysis, and J. Tang for discussion in SEM imaging. C.L-R. acknowledges her secondary supervisor J. Phillips (UCL). We also acknowledge J. Phillips for the gift of astrocytes. M.M.S. is also affiliated to the Department of Medical Biochemistry and Biophysics, Karolinska Institute, Sweden. Funding: L.O. and M.M.S. acknowledge the financial support from Engineering and Physical Sciences Research Council (EPSRC) Programme Grant "Engineering Growth Factor Microenvironments - A New Therapeutic Paradigm for Regenerative Medicine" (EP/P001114/1). J.P.K.A. acknowledges support from the Medical Research Council (MRC) (MR/S00551X/1). J.P.W. and M.M.S. acknowledge the financial support from the UK Regenerative Medicine Platform "Acellular / Smart Materials - 3D Architecture" (MR/R015651/1). M.M.S. and Y.L. acknowledge support from the Wellcome Trust Senior Investigator Award (098411/Z/12/Z). C.L-R. acknowledges funding from EPSRC studentship "Development of New Biomaterials for Regenerative Medicine" (no. 1975740). D.H. acknowledges funding from the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 839111. Author contributions: L.O. designed the study and performed the experiments. M.M.S. supervised the study. L.O. and J.P.K.A. wrote the manuscript with input from other authors. J.P.K.A., Y.L., and J.A.B. contributed to the scientific discussion. Y.L., J.P.W., D.H., and J.A.B. contributed to the distribution of polymers. J.P.K.A. and C.L-R. contributed to the isolation and distribution of primary cells. K.Z. contributed to the SEM imaging. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Raw research data are available online at DOI: 10.5281/zenodo.3932099.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.