Additively manufactured BaTiO3 composite scaffolds: A novel strategy for load bearing bone tissue engineering applications

Abstract

Piezoelectric ceramics, such as BaTiO₃, have gained considerable attention in bone tissue engineering applications thanks to their biocompatibility, ability to sustain a charged surface as well as improve bone cells' adhesion and proliferation. However, the poor processability and brittleness of these materials hinder the fabrication of three-dimensional scaffolds for load bearing tissue engineering applications. For the first time, this study focused on the fabrication and characterisation of BaTiO₃ composite scaffolds by using a multi-material 3D printing technology. Polycaprolactone (PCL) was selected and used as dispersion phase for its low melting point, easy processability and wide adoption in bone tissue engineering. The proposed single-step extrusion-based strategy enabled a faster and solvent-free process, where raw materials in powder forms were mechanically mixed and subsequently fed into the 3D printing system for further processing. PCL, PCL/hydroxyapatite and PCL/BaTiO₃ composite scaffolds were successfully produced with high level of consistency and an inner architecture made of seamlessly integrated layers. The inclusion of BaTiO₃ ceramic particles (10% wt.) significantly improved the mechanical performance of the scaffolds (54 ± 0.5 MPa) compared to PCL/hydroxyapatite scaffolds (40.4 ± 0.1 MPa); moreover, the presence of BaTiO₃ increased the dielectric permittivity over the entire frequency spectrum and tested temperatures. Human osteoblasts Saos-2 were seeded on scaffolds and cellular adhesion, proliferation, differentiation and deposition of bone-like extracellular matrix were evaluated. All tested scaffolds (PCL, PCL/hydroxyapatite and PCL/BaTiO₃) supported cell growth and viability, preserving the characteristic cellular osteoblastic phenotype morphology, with PCL/BaTiO₃ composite scaffolds exhibiting higher mineralisation (ALP activity) and deposited bone-like extracellular matrix (osteocalcin and collagen I). The single-step multi-material additive manufacturing technology used for the fabrication of electroactive PCL/BaTiO₃ composite scaffolds holds great promise for sustainability (reduced material waste and manufacturing costs) and it importantly suggests PCL/BaTiO₃ scaffolds as promising candidates for load bearing bone tissue engineering applications to solve unmet clinical needs.

Keywords: Additive manufacturing; Barium titanate; Bone tissue engineering; Composite scaffolds; Extrusion-based technology; PCL.