Bone Regeneration in Calvaria Defects in a Rat Model by Implantation of Offset and Gradient Melt Electrowritten PCL Scaffolds

Introduction: Autologous bone grafts to repair critical defects is an expensive treatment strate­gy associated with significanl surgical morbidity. Various tissue engineering approaches using scaffolds produced by additive manufacturing techniques when combined with osleoblast cells, has shown promising results. Our previous studies have shown porous scaffolds with a gradient porous architecture mimicking the gradient bone density in native cortical and cancellous bones, or 30% and 50% displaced offset structures. stimulated osteogenesis and cell proliferation com­pared to homogenous structures. This study aimed to assess the effectiveness of these scaf­
folds in vivo to promote osseous healing.
Materials and Methods: Three-dimensional melt electrowritten e-poly caprolactone (PCL) scaf­folds with a 500 µm homogenous, 50% offset or gradient architecture were coated with CaP
before implantation into a rodent critical-sized calvarial defect for 4 and 8 weeks. At the end of this healing period, samples were collected and the correlation between the scaffold pore size and bone regeneration was assessed by examining bone density and the expression of the an­giogenesis and osteogenic markers.
Results: Micro-CT and H&E staining showed more new bone formation in the 500 µm and gra­dient architecture scaffolds 8 weeks post-implantation due to the better supply of nutrients and 02 as a result of the larger pores and the more nearly imitating native bone structure. lmmuno­histochemistry analysis showed expression of representative osteogenic and angiogenic mark­ers by the newly formed bone. Of the scaffolds. the gradient architecture showed superior Colla­gen I, OPN. OCN and vWF expression compared to the other groups.
Conclusions: Melt electrowritten scaffolds with a gradient pore design is a promising approach to promote bone formation.