Magnetically-assisted 3D bioprinting of anisotropic tissue-mimetic constructs

Recreating the extracellular matrix organization and cellular patterns of aniso-tropic tissues in bioengineered constructs remains a significant biofabrication challenge. Magnetically-assisted 3D bioprinting strategies can be exploited to fabricate biomimetic scaffolding systems, but they fail to provide control over the distribution of magnetic materials incorporated in the bioinks while pre-serving the fidelity of the designed composites. To overcome this dichotomy, the concepts of magnetically- and matrix-assisted 3D bioprinting are combined here. By allowing low viscosity bioinks to remain uncrosslinked after printing, this approach enables the arrangement of incorporated magnetically-responsive microfibers without compromising the resolution of printed structures before inducing their solidification. Moreover, the fine design of these magnetic microfillers allows the use of low inorganic contents and weak magnetic field strengths, minimizing the potentially associated risks. This strategy is evalu-ated for tendon tissue engineering purposes, demonstrating that the synergy between the biochemical and biophysical cues stemming from a tendon-like anisotropic fibrous microstructure, combined with remote magneto-mechanical stimulation during in vitro maturation, is effective on directing the fate of the encapsulated human adipose-derived stem cells toward tenogenic pheno-type. In summary, the developed strategy allows the fabrication of anisotropic high-resolution magnetic composites with remote stimulation functionalities, opening new horizons for tissue engineering applications.The authors acknowledge the financial support from project NORTE-01-0145-FEDER 000021 supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); the European Union Framework Program for Research and Innovation HORIZON 2020, under the Twinning grant agreement no. 810850-Achilles, European Research Council grant agreement no. 772817, Fundação para a Ciência e a Tecnologia for the PhD grants PD/BD/129403/2017 (S.M.B.) and PD/BD/143039/2018 (S.P.B.T.) financed through doctoral the program in Tissue Engineering, Regenerative Medicine and Stem Cells (TERM&SC), for 2020.03410. CEECIND (R.M.A.D.) and project PTDC/NAN-MAT/30595/2017. Xunta de Galicia and Ministerio de Universidades (Spain) for postdoctoral grants ED481B2019/025 (A.P.) and Margarita Salas (R.R.), respectively. Schematics in Figures 1 and 5 were created with BioRender.com