3D printing of hybrid biomaterials for bone tissue engineering: Calcium-polyphosphate microparticles encapsulated by polycaprolactone

Here we describe the formulation of a morphogenetically active bio-ink consisting of amorphous microparticles (MP) prepared from Ca2+ and the physiological inorganic polymer, polyphosphate (polyp). Those MP had been fortified by mixing with poly-epsilon-caprolactone (PCL) to allow 3D-bioprinting. The resulting granular PCL/Ca-polyP-MP hybrid material, liquefied by short-time heating to 100 degrees C, was used for the 3D-printing of tissue-like scaffolds formed by strands with a thickness of 400 mu m and a stacked architecture leaving approximate to 0.5 mm(2)-sized open holes enabling cell migration. The printed composite scaffold turned out to combine suitable biomechanical properties (Young's modulus of 1.60 +/- 0.1 GPa; Martens hardness of 153 +/- 28 MPa), matching those of cortical and trabecular bone, with morphogenetic activity. This scaffold was capable of attracting and promoting the growth of human bone-related SaOS-2 cells as demonstrated by staining for cell viability (Calcein AM), cell density (DRAQ5) and SEM studies. Furthermore, the hybrid material was demonstrated to upregulate the steady-state-expression of the cell migration-inducing chemokine SDF-1 alpha. EDX analysis and FTIR measurements revealed the presence of hydroxyapatite in the mineral deposits formed on the scaffold surface. Based on the results we conclude that granular PCL/Ca-polyP-MP hybrid material is suitable for the fabrication of bioprintable scaffold which comprises not only biomechanical stability but also morphogenetic potential. Statement of Significance In present-day regenerative engineering efforts, biomaterial- and cell-based strategies are proposed that meet the required functional and spatial characteristics and variations, especially in the transition regions between soft (cartilage, tendon or ligament) and hard (bone) tissues. Statement of Significance: In a biomimetic approach we succeeded to fabricate amorphous Ca-polyP nanoparticles/microparticles which are highly biocompatible. Together with polycaprolactone (PCL), polyP can be bio-printed. This hybrid material attracts the cells, as documented optically as well as by a gene-expression studies. Since PCL is already a FDA-approved organic and inert polymer and polyp a physiological biologically active component this new bio-hybrid material has the potential to restore physiological functions, including bone remodelling and regeneration if used as implant. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.