Local microarchitecture affects mechanical properties of deposited extracellular matrix for osteonal regeneration

Multiple biomimetic approaches have been attempted to accelerate the regeneration of functional bone tissue. While most synthetic scaffolds are designed to mimic the architecture of trabecular bone, in the current study, cortical bone-like extracellular matrix was regenerated in vitro within organized structures. Biphasic calcium phosphate (BCaP) and hydroxyapatite (HAp) scaffolds were developed with longitudinal microchannels (250 μm diameter) that resembled native osteons in cortical bone. BCaP and HAp scaffolds had a compressive strength of 7.61 ± 1.42 and 9.98 ± 0.61 MPa respectively. The constructs were investigated in vitro to evaluate the organization and stiffness of the extracellular matrix (ECM) formed by human fetal osteoblasts (HFObs) cultured inside the microchannels. The ECM deposited on the BCaP scaffolds was found to have a higher micro-hardness (h) (1.93 ± 0.40 GPa) than the ECM formed within the HAp microchannels (h = 0.80 ± 0.20 GPa) (p < 0.05) or native bone (h = 0.47–0.74 GPa). ECM deposition within the microchannels resembled osteoid organization and showed a significant increase in both osteoid area and thickness after 24 days (p < 0.001). These observations indicate that controlled microarchitecture, specifically cylindrical microchannels, plays a fundamental role in stimulating the appropriate cellular response aimed at recreating organized, cortical bone-like matrix. These findings open the door for researchers to develop a new generation of cortical bone scaffolds that can restore strong, organized bone.