Enzyme-induced mineralization of calcium carbonate in 3D printable granular hydrogels

Abstract Many biological materials, such as bone, are organic-inorganic composites, made from a polymeric matrix that supports biomineralization under mild conditions. These materials are usually composed of a small set of abundant components like polysaccharides, proteins, and minerals, and exhibit a remarkable combination of density normalized stiffness, toughness, and functionality. Producing bio-inspired synthetic porous composites with a similar combination of properties through energy-efficient processes still presents an unmet challenge. Some aspects of this challenge can be addressed using living bacteria that induce biomineralization. However, living bacteria limit biomedical applications, especially in vivo, require careful handling, and are costly. To address these limitations, we introduce enzyme-containing granular precursors exclusively made from naturally sourced polymers. These precursors can be cast or direct ink written into cm-sized structures before they are mineralized under benign conditions to reach CaCO 3 contents up to 92 wt% with a porosity of 56 vol%. The resulting mineralized scaffolds exhibit a compressive strength up to 4 MPa (specific: 5.2 MPa·cm 3 ·g − 1 ) and a compressive modulus of 56 MPa (specific: 72 MPa·cm 3 ·g − 1 ). Although measured in the dry state, these values fall within the range reported for human trabecular bone with similar porosities (50–90% (Morgan et al., Annu Rev Biomed Eng 20:119–43, 91; Tanoto et al., Extreme Mech Lett 73:102265, 92). The resulting biomineral-organic composites show low cytotoxicity. These findings highlight the potential of this approach to 3D print biocompatible CaCO 3 -based composites under mild conditions. We envisage this formulation to open up new possibilities for tissue engineering.