Bioinspired Nanoscale 3D Printing of Calcium Phosphates Using Bone Prenucleation Clusters

Calcium phosphates (CaPs) are ubiquitous in biological structures, such as vertebrate bones and teeth, and have been widely used in biomedical applications. However, fabricating CaPs at the nanoscale in 3D has remained a significant challenge, particularly due to limitations in current nanofabrication techniques, such as two-photon polymerization (2pp), which are not applicable for creating CaP nanostructures. In this study, a novel approach is presented to 3D print CaP structures with unprecedented resolution of ≈300 nm precision, achieving a level of detail three orders of magnitude finer than any existing additive manufacturing techniques for CaPs. This advancement is achieved by leveraging bioinspired chemistry, utilizing bone prenucleation nanoclusters (PNCs, average size of 5 nm), within a photosensitive resin. These nanoclusters form a highly transparent photoresist, overcoming the light-scattering typically associated with larger calcium phosphate-based nanoparticles. This method not only allows for nanopatterning of CaPs on diverse substrates, but also enables the precise control of microstructure down to the level of submicron grains. The method paves the way for the developing of bioinspired metamaterials, lightweight damage-tolerant materials, cell-modulating interfaces, and precision-engineered coatings.