Effect of filler size distribution on the mechanical and biological properties of biomimetic bone composites fabricated by solvent-based extrusion bioprinting

Biomimetic composites for bone tissue engineering have outstanding potential to improve bone grafting and in vitro drug testing. Although bioactive fillers play a crucial role in those composites, the impact of their physical properties on final products is not fully understood, particularly when using solvent-based extrusion bioprinting (SBEB). In our study, we used ball-milled bioactive glass and hydroxyapatite powders to examine how particle size distribution impacts the flow, mechanical, and biological properties of biomaterials produced via SBEB. The polymeric matrix of polycaprolactone (PCL) was dissolved in solvents, and the fillers were mixed in different proportions to optimize the biomaterial ink's extrudability and interphase bonding. The printed samples were subjected to mechanical testing, solvent removal, and cytotoxicity analysis. Our results show that powders milled at 25 Hz for 10 min in a dry medium produced homogeneous size distributions with low agglomeration. A 50% PCL and 50% w/w polymer-to-filler ratio in an 80% w/v solid–liquid proportion generated the best extrudability and interphase bonding. Particle type affected the modulus of elasticity, and smaller aggregate sizes increased ultimate tensile strength. Moreover, the specific size of the filler particles and their structure could influence their affinity to solvents, thereby resulting in variation in the solvent removal process after ethanol rinsing. Beyond that, the biomaterials were non-cytotoxic and demonstrated high cell viability. Those findings highlight the importance of controlling the filler size distribution to optimize the mechanical, rheological, and biological properties of biomaterials fabricated using SBEB for bone tissue engineering applications.