Designed Microbial Biosynthesis of Hierarchical Bone-Mimetic Biocomposites in 3D-Printed Soft Bioreactors

The creation of 3D biomimetic composite structures has important applications in tissue engineering, lightweight structures, drug delivery, and sensing. Previous approaches in fabricating 3D biomimetic composites have relied on blending or assembling chemically synthesized molecules or structures, making it challenging to achieve precise control of the size, geometry, and internal structure of the biomimetic composites. Here, we present a new approach for the creation of 3D bone-mimetic biocomposites with precisely controlled shape, hierarchical structure, and functionalities. Our approach is based on the integration of programmable microbial biosynthesis with 3D printing of gas-permeable and customizable bioreactors. The organic and inorganic components are bacterial cellulose and calcium hydroxyapatite via a mineral precursor, which are generated by Komagataeibacter xylinus and Bacillus simplex P6A, respectively, in 3D-printed silicone bioreactors in consecutive culturing cycles. This study is of high significance to biocomposites, biofabrication, and tissue engineering as it paves the way for the synergistic integration of microbial biosynthesis and additive manufacturing.