3D-Printed Porous Hydroxyapatite Formed via Enzymatic Mineralization

Bone is a hierarchically organized, lightweight tissue that combines remarkable mechanical resilience with low density and can be repaired if damaged. This fascinating combination of properties arises from the hierarchical structure of bone and its locally changing composition, enabled by the controlled growth of hydroxyapatite (HA) crystals within a collagen-rich extracellular matrix. Inspired by the excellent density-normalized mechanical properties of bone, a lot of excellent work has been devoted to the fabrication of porous HA-based materials that can be used, for example, as bone graft substitutes. However, their fabrication typically involves high-temperature sintering, which is energy-intensive and restricts the incorporation of biologically active components that are typically thermo-labile. These processing limitations hinder scalability and reduce the potential for integration with living tissue, presenting a critical challenge in the development of clinically relevant bone repair materials. Here, we introduce an enzyme-mediated strategy to 3D print load-bearing porous HA-based composites through an energy-efficient, benign process that is conducted at room temperature. Alkaline phosphatase (ALP), an enzyme relevant to bone formation, is embedded in naturally derived hydrogel microfragments and mixed with enzyme-free fragments included to tune the porosity of the final composite. The jammed microfragments are 3D printed in air at room temperature and subsequently mineralized under mild aqueous conditions. The resulting scaffolds exhibit up to 52 vol% porosity, compressive strengths of 3.65 MPa (5.5 MPa·g⁻¹·cm³ specific strength), and low cytotoxicity toward osteoblasts. This sintering-free approach offers control over porosity and mineral distribution and enables the fabrication of biocompatible, low-density mineralized architectures under physiological conditions. We foresee the combination of mechanical performance, bioactivity, and benign, energy-efficient processing to open up new avenues for bone tissue engineering and mineral repair applications where broken structures have the potential to bear significant loads much faster than currently available solutions do.