The balance of ‘outside–in’ and ‘inside–out’ signaling is critical in tissue development and regeneration. This Comment highlights emerging strategies to engineer and manipulate this delicate equilibrium and fine-tune cellular responses using complementary tools in biomaterials design and synthetic biology.
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References
Lutolf, M. P. & Hubbell, J. A. Nat. Biotechnol. 23, 47–55 (2005).
Hernandez-Gordillo, V. et al. Biomaterials 254, 120125 (2020).
Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J. & Shenoy, V. B. Nature 584, 535–546 (2020).
Novak, R. et al. Nat. Biomed. Eng. 4, 407–420 (2020).
Gaspar, V. M., Lavrador, P., Borges, J., Oliveira, M. B. & Mano, J. F. Adv. Mater. 32, e1903975 (2020).
Lee, M., Rizzo, R., Surman, F. & Zenobi-Wong, M. Chem. Rev. 120, 10950–11027 (2020).
Gjorevski, N. et al. Science 375, eaaw9021 (2022).
Takahashi, K. & Yamanaka, S. Cell 126, 663–676 (2006).
Doudna, J. A. & Charpentier, E. Science 346, 1258096 (2014).
Anzalone, A. V. et al. Nature 576, 149–157 (2019).
Li, H. S. et al. Science 378, 1227–1234 (2022).
Hasty, J., McMillen, D. & Collins, J. J. Nature 420, 224–230 (2002).
Deisseroth, K. Nat. Methods 8, 26–29 (2011).
Morsut, L. et al. Cell 164, 780–791 (2016).
Ruskowitz, E. R. et al. Nat. Chem. 15, 694–704 (2023).
Acknowledgements
This work was supported by the grants from the National Institutes of Health, Maximizing Investigators’ Research Award (R35GM138036, C.A.D.) and R01 (DE016523 and DK12092, K.S.A.), the National Science Foundation (RECODE 2033723, K.S.A.), and the Defense Advanced Research Projects Agency (W911NF-19-2-004, K.S.A. and B.E.K.).
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All authors contributed to the initial writing and subsequent editing of this manuscript. C.A.D. prepared the figures with input from B.E.K. and K.S.A.
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DeForest, C.A., Kirkpatrick, B.E. & Anseth, K.S. Engineering native biological complexity from the inside–out and outside–in. Nat Chem Eng 1, 2–5 (2024). https://doi.org/10.1038/s44286-023-00013-1
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DOI: https://doi.org/10.1038/s44286-023-00013-1