High-resolution fabrication of amorphous calcium phosphate-reinforced polycaprolactone composite scaffolds for bone tissue engineering

Abstract:

Calcium phosphate-reinforced polycaprolactone composites have gained a grown attention for the fabrication of bioresorbable scaffolds for bone tissue engineering. One limitation arose from the low lateral resolution of the conventional fused filament fabrication, which was overcome in this study by the implementation of advanced three-stage method of the polycaprolactone–amorphous calcium phosphate scaffold formation. Another challenge emerged from poor cell adhesion to the composite surface and low osteoinductivity, that was addressed by the surface modification approaches and the implementation of more soluble dispersed phase (amorphous calcium phosphate). Stabilized amorphous calcium phosphate nanoparticles were synthesized with three different carboxylate stabilizers. The addition of amorphous calcium phosphate led to the improved bending and tensile strength, disclosing the considerable interfacial binding energy between particles and polymer matrix. Furthermore, the modification of developed composites in acidic environment improved the stiffness, while alkaline treatment was shown to decrease stiffness and enhance roughness, providing additional cell adhesion sites. Applied three-stage composite scaffold fabrication method was shown to provide smooth rounded pores. The cytocompatibility assay showed the absence of negative effects from the modified amorphous calcium phosphate dispersed phase on the metabolic activity of mesenchymal stromal cells and revealed considerable cell adhesion on the composite surface with no negative effects on the mesenchymal stromal cells viability and morphology. Thus, developed fabrication method in combination with the proposed polycaprolactone-amorphous calcium phosphate composition showed enhanced mechanical and surface properties, as well as biocompatibility, providing a mineral-supportive microenvironment relevant to bone regeneration.

Bone tissue engineering; Additive manufacturing; Polycaprolactone composites; Osteoconductive scaffolds; Low pressure injection molding; Amorphous calcium phosphate.