Cytomimetic calcification in chemically self-regulated prototissues

Rui Sun, Zhuping Yin, Molly M. Stevens, Mei Li () and Stephen Mann ()
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Rui Sun: University of Bristol
Zhuping Yin: University of Bristol
Molly M. Stevens: Karolinska Institute
Mei Li: University of Bristol
Stephen Mann: University of Bristol

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract The fabrication of cytomimetic materials capable of orchestrated and adaptive functions remains a significant challenge in bottom-up synthetic biology. Inspired by the cell/matrix integration of living bone, here we covalently tether distributed single populations of alkaline phosphatase-containing inorganic protocells (colloidosomes) onto a crosslinked organic network to establish viscoelastic tissue-like micro-composites. The prototissues are endogenously calcified with site-specific mineralization modalities involving selective intra-protocellular calcification, matrix-specific extra-protocellular calcification or gradient calcification. To mirror the interplay between osteoblasts and osteoclasts, we prepare integrated prototissues comprising a binary population of enzymatically active colloidosomes capable of endogenous calcification and decalcification and utilize chemical inputs to induce structural remodelling. Overall, our methodology opens a route to the chemically self-regulated calcification of homogeneous and gradient tissue-like mineral-matrix composites, advances the development of bottom-up synthetic biology in chemical materials research, and could provide potential opportunities in bioinspired tissue engineering, hydrogel technologies and bone biomimetics.

Date: 2025
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DOI: 10.1038/s41467-025-59251-x

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