  Critically sized defects are currently treated via autologous or allograft
bone grafting, distraction osteogenesis, and membrane induction. However, these
methods have major weaknesses which encourage the development of synthetic bone
graft substitutes. A bioresorbable and physiologically load sustaining graft
substitute was fabricated from polylactic acid using 3D printing, a versatile
method which enables parameters to be customizable in a patient-specific
manner. The internal architecture consists of vertical and horizontal conduits
that are organized to achieve gradients in porosity and pore size in the radial
direction to emulate cortical bone encapsulating cancellous bone. A diameter of
30mm and height of 10mm was designed to target the repair of critically sized
long bone defects. The compressive properties of these graft substitutes were
determined to be comparable to adult human femurs. Furthermore, dynamic fatigue
testing at twice the human torso weight (800N) indicated that the bone graft
substitute achieved stability as quickly as 200,000 cycles, suggesting its
ability to support weight bearing loads while it gradually degrades as bone
cells proliferate and mineralize. Additionally, the graft substitutes were
seeded with human fetal osteoblasts to validate homogenous cellular attachment
and cytocompatibility. Graft substitutes were also dynamically cultured for 28
days under various loading regimens using human mesenchymal stem cell
differentiated osteoblasts, and these resulting tissue constructs were
subjected to fatigue testing. The frequency of loading during dynamic culturing
had a profound effect on the rate of mineralization which was particularly high
at 2Hz, confirmed by Alizarin Red staining of the calcium deposits. Taken
together, these bone graft substitutes have potential for use as orthopaedic
implants to facilitate the repair of critically sized bone defects.
