Publications

Doping of calcium phosphates (CaPs) with bioinorganic ions is a widely used strategy to enhance their biological performance in bone regeneration. However, conventional methods for ionic incorporation in CaP scaffolds often require high-temperature treatments or involve multiple complex steps. Here, we present two simple strategies to dope 3D-printed CaP scaffolds via incorporation of ions into the apatitic phase during the hydrolysis of alpha-tricalcium phosphate (alpha-TCP) to calcium deficient hydroxyapatite (CDHA). In the first strategy, ions were incorporated directly into the printing ink, whereas in the second, undoped robocasted scaffolds were immersed in ionic solutions, allowing ion incorporation into precipitated CDHA during phase transformation. We investigated several ions, including strontium (Sr2+), magnesium (Mg2+), silicon (SiO44- ) and gallium (Ga3+). Sr2+ and Ga3+ were successfully incorporated into the scaffolds, either by direct ink doping (Sr2+) or by soaking in ionic solutions (Sr2+ and Ga3+). Direct incorporation of Sr2+ in the ink resulted in a higher ion loading and release, enhancing bone formation and bone quality, as evidenced by increased mineral-to-matrix ratio and Young's modulus, as well as osteoinductive properties relative to non-doped scaffolds. Furthermore, we demonstrated for the first time the osteoinductive capacity of Ga3+ in an ectopic in vivo model.

JTD Keywords: 3d printing, Apatite, Biomimetic hydroxyapatite, Bone regeneration, Calcium phosphates, Calcium-phosphate cement, Differentiation, Ion doping, Magnesium-deficiency, Microporosity, Nanocrystals, Osteoinduction, Scaffold, Silicon, Substituted hydroxyapatite, Vitro

Concave surfaces have shown to promote bone regeneration in vivo. However, bone scaffolds obtained by direct ink writing, one of the most promising approaches for the fabrication of personalized bone grafts, consist mostly of convex surfaces, since they are obtained by microextrusion of cylindrical strands. By modifying the geometry of the nozzle, it is possible to print 3D structures composed of non-cylindrical strands and favor the presence of concave surfaces. In this work, we compare the in vivo performance of 3D-printed calcium phosphate scaffolds with either conventional cylindrical strands or star-shaped strands, in a rabbit femoral condyle model. Mono cortical defects, drilled in contralateral positions, are randomly grafted with the two scaffold configurations, with identical composition. The samples are explanted eight weeks post-surgery and assessed by ??-CT and resin embedded histological observations. The results reveal that the scaffolds containing star-shaped strands have better osteoconductive properties, guiding the newly formed bone faster towards the core of the scaffolds, and enhance bone regeneration, although the increase is not statistically significant (p > 0.05). This new approach represents a turning point towards the optimization of pore shape in 3D-printed bone grafts, further boosting the possibilities that direct ink writing technology offers for patient-specific applications.

JTD Keywords: 3d printing, biomimetic calcium phosphate, bone regeneration, in vivo, pore architecture, 3d printing, Architecture, Biomimetic calcium phosphate, Bone regeneration, Calcium-phosphate scaffolds, Geometry, Growth, Implants, In vivo, Induction, Microporosity, Osteoinduction, Pore architecture, Scaffold, Surfaces, Tissue