Bovine serum albumin-modified 3D printed alginate dialdehyde-gelatin scaffolds incorporating polydopamine/SiO 2 -CaO nanoparticles for bone regeneration.

Three-dimensional (3D) printing allows precise manufacturing of bone scaffolds for patient-specific applications and is one of the most recently developed and implemented technologies. In this study, a bilayer and multimaterial alginate dialdehyde-gelatin (ADA-GEL) scaffolds incorporating polydopamine (PDA)/SiO2 -CaO nanoparticle complexes was 3D printed using a pneumatic extrusion-based 3D printing technology and further modified on the surface with bovine serum albumin (BSA) for application in critical-sized bone regeneration. The morphology, chemistry, and in vitro bioactivity of PDA/SiO2 -CaO nanoparticle complexes were characterized (n = 3) and compared with the mesoporous SiO2 -CaO nanoparticles. Successful deposition of the PDA layer on the surface of the SiO2 -CaO nanoparticles allowed better dispersion in a liquid medium and showed enhanced bioactivity. Rheological studies (n = 3) of ADA-GEL inks consisting of PDA/SiO2 -CaO nanoparticle complexes showed results that may indicate better injectability and printability behavior compared to ADA-GEL inks consisting of unmodified nanoparticles. Microscopic observations of 3D printed scaffolds revealed that PDA/SiO2 -CaO nanoparticle complexes introduced additional topography onto the surface of 3D printed scaffolds. Additionally, the modified scaffolds were mechanically stable and elastic, closely mimicking the properties of a natural bone. Furthermore, protein-coated bilayer scaffolds displayed controllable absorption and biodegradation, enhanced bioactivity, MC3T3-E1 cell adhesion, proliferation, and higher alkaline phosphatase (ALP) activity (n = 3) compared to unmodified scaffolds. Consequently, the present results confirm that ADA-GEL scaffolds incorporating PDA/SiO2 -CaO nanoparticle complexes modified with BSA offer a promising approach for bone regeneration applications.