Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo

Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(e-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specifi c to human ligament progenitor cells and assess their ability to form aligned bone-ligament-cementum complexes in vivo. PCL scaffolds are designed to integrate a 3D printed bone region with a micropatterned PCL thin fi lm consisting of grooved pillars. The patterned fi lm region is seeded with human ligament cells, fi broblasts transduced with bone morphogenetic protein-7 genes seeded within the bone region, and a tooth dentin segment positioned on the ligament region prior to subcutaneous implantation into a murine model. Results indicate increased tissue alignment in vivo using micropatterned PCL fi lms, compared to random-porous PCL. At week 6, 30 mu m groove depth signifi cantly enhances oriented collagen fi ber thickness, overall cell alignment, and nuclear elongation relative to 10 MU m groove depth. This study demonstrates for the fi rst time that scaffolds with combined hierarchical mesoscale and microscale features can align cells in vivo for oral tissue repair with potential for improving the regenerative response of other bone-ligament complexes.