E3 - Mechanics of 3D Printed Bone Tissue Scaffolds with Tunable Anisotropy

Introduction: : Recent advancements in 3D printing/additive manufacturing are enabling the widespread design of engineered structures with tunable lattice configurations for biomedical applications. Lattices designed as bone tissue scaffolds provide in vivo mechanical support while facilitating biological tissue growth by mimicking bone’s geometry and mechanical properties. However, challenges remain in designing 3D printed scaffolds due to complexities for efficiently modulating loads in the human body while supporting biological growth. For instance, many loading conditions throughout the human body are asymmetric, as evidenced by bone’s anisotropic mechanical properties.

Bone tissue scaffolds are typically designed with isotropic effective properties and mechanical stiffness tuned to match aggregate bone properties with porosities between 50% to 90%. Isotropic tissue scaffolds are limited, however, because they do not mimic anatomical bone’s adaption to asymmetric physiological loads, such as preferential loading along the spine. When considering these factors, an anisotropic bone scaffold design is proposed in Figure 1 to facilitate spinal fusion by tuning unit cell aspect ratio. The anisotropy of the scaffold enables tuning of mechanics for higher stiffness aligned with the spine that allows greater transverse porosity for tissue growth to improve system-wide mechanical and biological functioning.

Here, we conduct an experimental investigation to design and characterize anisotropy in 3D printed lattices by altering their unit cell aspect ratios, to create tunable tissue scaffolds that mimic bone’s anisotropic properties with mechanically efficient structures. Such scaffolds are poised to improve mechanical and biological functioning of scaffolds through directional optimization of properties suitable for bone regeneration.

Materials and

Methods: : Lattices were designed by generating unit cells of varied aspect ratios with Abaqus software (version 6.19-1) with automation through python. Unit cells were generated by arranging beams with octagonal cross-sections in a tetragonal volume to form unit cells with a BC-Tetra topology. Unit cells were patterned to form lattice scaffolds by placing unit cells of the same design adjacent to one another with shared edge beams and faces in a three-dimensional patterning along x, y, and z axes. Hierarchical scaffolds were designed by removing central unit cells from lattices to form hierarchical pores referred to as large voids.

Lattice structures were fabricated using an Envision One cDLP printing system (EnvisionTec, Dearborn, MI, USA) with a DLP fabrication process. All lattices were fabricated using E-Shell 600 resin (EnvisionTEC). E-shell 600 is a biocompatible material primarily composed of acrylates/methacrylates that have been experimentally demonstrated to support bone tissue growth.

All mechanical tests were conducted using an Instron 5966 universal testing machine (Instron, Norwood, MA, USA). Uniaxial compression tests were conducted according to the ISO-13314 standard protocol. All testing was conducted using a loading rate of 0.1 strain per minute until yielding to determine the effective elastic moduli in longitudinal and transverse orientations.

Results, Conclusions, and Discussions:: Anisotropic mechanics of lattices were first investigated to determine their effective material property ranges for use as bone tissue scaffolds. BC-Tetra unit cells were generated with 70% porosity relevant for bone tissue engineering and patterned to form volume-controlled lattices of approximately 1 cm height and 1 cm width (Fig. 2). The effective elastic modulus in the longitudinal direction (Ez) increases with unit cell aspect ratio because an increase in unit cell height results in a greater proportion of diagonal beams aligned with longitudinal loading, while the opposite is true for the transverse direction (Ex). These findings demonstrate the feasibility for altering lattice behavior based on unit cell design to tune anisotropic mechanics, which enables a mimicking of bone’s anisotropic properties in multiple directions.

Hierarchical scaffolds consisting of high aspect ratio unit cells with height of ~5 mm were designed for 50% and 70% porosities and diameters of 500 and 800 µm. Void size varied based on the total number of unit cells patterned to form scaffolds. Representative samples for all printed designs are presented in Figure 3. Results demonstrate all designs qualitatively printed, but solidification of pores was observed in a greater proportion of pores in scaffolds with no voids. Testing of these scaffolds demonstrated stiffness from 3.9 to 8.4 kN/mm, suitable for bone fusion.

It is predicted that the hierarchical voids could improve nutrient transport and vascularization throughout the structure while anisotropic unit cell geometries could support finer control over the rate that tissues grow within a scaffold. Further considerations and studies, especially those with in vitro and in vivo experiments, are necessary to fully validate the technology and ensure optimized functioning. Future research can build on these findings to identify strategies for effective anisotropy in scaffolds to improve regenerative medicine treatments enabled by additive manufacturing.

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