Diatoms are unicellular eukaryotic algae that have a distinctive siliceous cell wall (frustule) with unique architectures. The nanotopography of the frustule is perfectly replicated between generations, offering a source of highly intricate and identical silica microparticles. In recent years, the ability to alter their cell wall chemistry both in terms of functionalisation with organic moieties or by incorporation of the metal ions in their frustules has increased interest in their utility for catalysis technologies, and semiconductor and biomedical applications. Herein we review the fundamental biological mechanisms in which diatoms produce their frustule and their ability to substitute different metal ions in their frustule fabrication process. The review focuses on the potential of diatom frustules as a naturally derived biomaterial in bone tissue engineering applications and how their cell walls, comprising biogenic silica, could either partially or fully incorporate other bone therapeutic metal ions, e.g., titanium or calcium, into their frustule. The use of diatom frustules in bone repair also potentially offers a ‘greener’, more environmentally friendly, biomaterial as they can naturally synthesise oxides of silicon and other metals into their frustules under ambient conditions at a relatively neutral pH. This process would negate the use of harsh organic chemicals and high-temperature processing conditions, often used in the fabrication of silica based biomaterials, e.g., bioactive glass.

In this study, bone tissue engineered scaffolds fabricated via powder-based 3D printing from hydroxyapatite (HA) and calcium sulphate (CaSO4) powders were investigated. The combination of using a fast resorbing CaSO4 based powder and the relatively slower HA powder represents a promising prospect for tuning the bioresorption of 3D printed (3DP) scaffolds. These properties could then be tailored to coincide with tissue growth rate for different surgical procedures. The manufactured scaffolds were infiltrated with poly(ε‑caprolactone) (PCL). The PCL infiltrated the inter-particle spacing within the 3DP structures due to the nature of a loosely-packed powder bed and also covered the surface of ceramic-based scaffolds. Consequently, the average compressive strength, compressive modulus and toughness increased by 314%, 465% and 867%, respectively. The resorption behaviour of the 3DP scaffolds was characterised in vitro using a high-throughput system that mimicked the physiological environment and dynamic flow conditions relevant to the human body. A rapid release of CaSO4 between Day 0 and 28 was commensurate with a reduction in scaffold mass and compressive properties, as well as an increase in medium absorption. In spite of this, HA particles, connected by PCL fibrils, remained within the microstructure after 56 days resorption under dynamic conditions. Consequently, a high level of structural integrity was maintained within the 3DP scaffold. This study presented a porous PCL-HA-CaSO4 3DP structure with the potential to encourage new tissue growth during the initial stages of implantation and also offering sufficient structural and mechanical support during the bone healing phase.