Optimizing rheological properties for printability: low-temperature extrusion 3D printing of hydroxyapatite-polycaprolactone mixture inks for bone tissue engineering

Abstract

Introduction: Low-temperature extrusion three-dimensional printing (LTE-3DP) using viscous ceramic-polymer inks has shown promise for bone tissue engineering. This process involves formulating a flowable ink by combining ceramic powders and other components with organic or inorganic polymer solutions, which can then be extruded through a 3D printer nozzle. LTE-3DP allows the incorporation of high fractions of bioactive ceramics and thermally labile additives such as drugs, proteins, and biomolecules into the inks to promote osteogenesis and bone regeneration. The rheology of the ink, influenced by various variables, significantly impacts the printability and form fidelity of the resulting scaffolds. These variables include the composition of the polymer solution and the size and weight ratio of ceramic microparticles. In this study, we posited that the printability of hydroxyapatite (HA) and polycaprolactone (PCL) mixture inks could be optimized by tailoring their rheological properties.Methods: We conducted a systematic investigation, varying the PCL weight percentage and HA:PCL weight ratio, to examine the effects of the ink’s composition on its viscosity and storage modulus, as well as its printability and the mechanical properties of 3D printed HA:PCL scaffolds.Results: We demonstrated that HA:PCL inks exhibit predictable non-Newtonian fluid behavior at higher fractions of HA, displaying significant shear thinning at elevated shear rates, which can facilitate extrusion through a 3D printing nozzle. We identified printable ink compositions based on filament continuity and scaffold form fidelity criteria. Moreover, we performed computational simulations to analyze the ink flow through an extrusion nozzle. These simulations utilized the Herschel-Bulkley-Papanastasiou constitutive model, considering the rheological properties obtained from experimental measurements. By combining experimental measurements and computational simulations, we formulated a non-dimensional Printability number that predicts whether an ink is printable based on the ink’s rheological parameters and printer-specific factors. Furthermore, we evaluated the compressive properties of printed HA:PCL scaffolds and characterized the effects of PCL% and HA:PCL ratio on the hyperelasticity observed in response to compressive deformations.Discussion: This hybrid approach using experimental rheology and FE simulations provides a framework to define the printability of ceramic-polymer ink formulations, which could help streamline the 3D printing of novel inks for bone tissue engineering.

Calcium Orthophosphate (CaPO4) Containing Composites for Biomedical Applications: Formulations, Properties, and Applications

“…By systematically varying the composition of HA:PCL inks, the authors demonstrated their non-Newtonian flow behavior and identified printable ink formulations based on their rheological properties. The weight ratio of HA in the PCL polymer was found to impact the compressive moduli and toughness of the prepared scaffolds [1140]. Similar results were obtained in another study, in which HA/PCL/polyethylene oxide inks both with and without adding vancomycin were prepared by a similar technique [1141].…”

“…Therefore, CaPO 4 -containing inks for 3D printing could also be considered as formulations belonging to either self-hardening biocomposites (Section 5.2) or injectable bone substitutes (Section 5.6); however, since the viscous inks are not designed for in vivo injections, biologically incompatible compounds (such as organic solvents) might be used in their composition because they will be eliminated afterward during either drying or later treatments. Several examples of typical CaPO 4 -containing formulations are described below [1133,[1140][1141][1142][1143][1144][1145][1146].…”

“…For example, HA/PCL inks were prepared by PCL dissolving in a ternary solvent prepared by mixing dichloromethane with the surfactant 2-butoxyethanol and plasticizer dibutyl phthalate in a volumetric ratio of 5:3:1, followed by addition of a HA powder through a 30-micron mesh sieve [1140]. The influence of important variables, such as the polymer type, concentration, solvent, additives, and ceramic particle characteristics, on the printability, shape fidelity, and mechanical properties of the 3D printed scaffolds was investigated.…”

3D Bioprinting of Sugar Beet Pectin through Horseradish Peroxidase-Catalyzed Cross-Linking

“…Additionally, a shear-thinning property was observed, as shown by the lower viscosity at higher shear rate (Figure ). The shear-thinning property of the SBP inks can be mediated by polymer chain alignment at a higher shear rate. , The shear-thinning property is important in extrusion-based printing since it allows ease of extrusion due to the decreasing viscosity in a higher shear rate, while also preventing the collapse of the construct due to their rapid recovery to high viscosity in the absence of shear rate postextrusion. − The shear-thinning property is also important to maintaining the viability of the cells in the bioink. It is well-known that high shear stress can damage the cells during the printing process. − The reduction in viscosity under shear strain decreases the shear stress applied to the cells in the bioinks during extrusion.…”