This study developed a non-equiatomic Ti_28.33Zr_28.33Hf_28.33Nb_6.74Ta_6.74Mo_1.55 super-solid solutionized BioHEA using laser powder bed fusion (LPBF) to reach the full potential as BioHEA. We succeeded in significant suppression of elemental segregation, thus, resulting in a single crystalline-like texture by activating layer-to-layer epitaxial growth. Relatively low Young’s modulus was achieved in the single crystalline-like BioHEA. Moreover, LPBF-fabricated BioHEA exhibited significantly higher yield stress (1355–1426 MPa) due to the effective solid solution hardening compared to as-cast counterpart with marked segregation (949 MPa), and good biocompatibility. This is first report achieving BioHEA with low modulus, excellent strength-ductility balance, and good biocompatibility via LPBF. GRAPHICAL ABSTRACT IMPACT STATEMENT This study achieved super-solid-solutionized and single crystalline-like TiZrHfNbTaMo bio-high entropy alloy using laser powder bed fusion, resulting in low Young’s modulus along oriented direction, excellent strength-ductility balance, and good cytocompatibility.

Anisotropic collagen/apatite microstructure is a prominent determinant of bone tissue functionalization; in particular, bone matrix modulates its anisotropic microstructure depending on the surrounding mechanical condition. Although mechanotransduction in bones is governed by osteocyte function, the precise mechanisms linking mechanical stimuli and anisotropic formation of collagen/apatite microstructure are poorly understood. Here we developed a novel anisotropic mechano-coculture system which enables the understanding of the biological mechanisms regulating the oriented bone matrix formation, which is constructed by aligned osteoblasts. The developed model provides bone-mimetic coculture platform that enables simultaneous control of mechanical condition and osteoblast-osteocyte communication with an anisotropic culture scaffold. The engineered coculture device helps in understanding the relationship between osteocyte mechanoresponses and osteoblast arrangement, which is a significant contributor to anisotropic organization of bone tissue. Our study showed that osteocyte responses to oscillatory flow stimuli regulated osteoblast arrangement through soluble molecular interactions. Importantly, we found that prostaglandin E2 is a novel determinant for oriented collagen/apatite organization of bone matrix, through controlling osteoblast arrangement.

Osteocytes are believed to play a crucial role in mechanosensation and mechanotransduction which are important for maintenance of mechanical integrity of bone. Recent investigations have revealed that the preferential orientation of bone extracellular matrix (ECM) mainly composed of collagen fibers and apatite crystallites is one of the important determinants of bone mechanical integrity. However, the relationship between osteocytes and ECM orientation remains unclear. In this study, the association between ECM orientation and anisotropy in the osteocyte lacuno-canalicular system, which is thought to be optimized along with the mechanical stimuli, was investigated using male rat femur. The degree of ECM orientation along the femur longitudinal axis was significantly and positively correlated with the anisotropic features of the osteocyte lacunae and canaliculi. At the femur middiaphysis, there are the osteocytes with lacunae that highly aligned along the bone long axis (principal stress direction) and canaliculi that preferentially extended perpendicular to the bone long axis, and the highest degree of apatite c-axis orientation along the bone long axis was shown. Based on these data, we propose a model in which osteocytes can change their lacuno-canalicular architecture depending on the mechanical environment so that they can become more susceptible to mechanical stimuli via fluid flow in the canalicular channel.

Metal additive manufacturing is a powerful tool for providing the desired functional performance through a three-dimensional (3D) structural design. Among the material functions, anisotropic mechanical properties are indispensable for enabling the capabilities of structural materials for living tissues. For biomedical materials to replace bone function, it is necessary to provide an anisotropic mechanical property that mimics that of bones. For desired control of the mechanical performance of the materials, we propose a novel 3D puzzle structure with cube-shaped parts comprising 27 (3 × 3 × 3) unit compartments. We designed and fabricated a Co–Cr–Mo composite structure through spatial control of the positional arrangement of powder/solid parts using the laser powder bed fusion (L-PBF) method. The mechanical function of the fabricated structure can be predicted using the rule of mixtures based on the arrangement pattern of each part. The solid parts in the cubic structure were obtained by melting and solidifying the metal powder with a laser, while the powder parts were obtained through the remaining nonmelted powders inside the structure. This is the first report to achieve an innovative material design that can provide an anisotropic Young’s modulus by arranging the powder and solid parts using additive manufacturing technology.