Biomechanical evaluation of mixed architecture hydroxyapatite scaffolds for bone tissue engineering

Bone tissue engineering aims at attempting to restore function and regenerate tissue by using synthetic materials to fabricate graft substitutes. It is targeted as an alternative to answer the increasingly unmet demand for autologous bone grafts. The objectives of this research were to optimize the design of 3 dimensional (3-D) hydroxyapatite (HA) scaffolds to increase both mechanical strength as well as fluid permeability and to understand the changes in the biomechanical properties of the scaffolds during the course of in vitro culture and in vivo implantation. Micro computed tomography (micro-CT) was used to compute scaffold architectural indices as a non-destructive predictor of scaffold biomechanical properties and to evaluate in vitro and in vivo changes.

The effect of variations in pore size and porosity on scaffold mechanical properties was evaluated by preparing 3-D trabecular like scaffolds of HA of four different pore sizes. Taking a cue from the cancellous---cortical organization of human bone, bilayer scaffolds were then prepared with outer cortical-like shells having a smaller pore size and inner trabecular-like cores having a larger pore size while maintaining a fully interconnected structure. A significant increase in mechanical compressive strength was observed between the bilayer architectures and the pure trabecular-like scaffolds. Permeability was measured for both the trabecular scaffolds and the bilayer scaffolds with a fixed volume ratio of outer cortical-like shell and inner trabecular-like core. It was observed that the permeability was highly dependent on the choice of the inner trabecular-like core. The micro-CT based architectural indices were used to predict both compressive strength as well as fluid permeability with high correlation. Changes in compressive strength and permeability were then measured after static in vitro cell culture on the trabecular-like porous scaffolds. It was observed that the deposition of extensive amounts of extra cellular matrix in the scaffolds during in vitro cell culture led to a significant multiple fold increase in compressive toughness. However, no significant change in permeability was observed for all the pore sizes evaluated. Finally, bilayer scaffolds were characterized for in vivo mechanical integrity using a rabbit radius segmental defect model. After 8 weeks implantation, no difference in mechanical strength, modulus or toughness of the scaffold was observed when compared to intact contralateral controls. Micro-CT evaluations indicated changes in cell attachment in vitro as well as tissue infiltration in vivo..

This research demonstrated the biomechanical optimization of scaffolds to both improve strength and retain permeability via a novel bilayer scaffold design. Micro-CT was demonstrated as a robust technology for evaluating architectural indices to predict scaffold mechanical properties and permeability with high correlation. It was also observed that micro-CT evaluations were sensitive to both in vitro and in vivo changes, and thus can be used as a design optimization tool in developing scaffold technology from laboratory benchtops to clinically relevant product development.