Applications of Prolyl Hydroxylase Inhibitors in Tissue Engineering and Regenerative Medicine

Abstract

Clinical applications of tissue engineering are limited mainly to thin or avascular tissues because of inadequate vascularization. In this project, we explored the incorporation of prolyl hydroxylase inhibitors (PHIs) into scaffolds as an alternative vascularization strategy. As a proof of concept, we conjugated the PHI pyridine-2,4-dicarboxylic acid (PDCA) to a gelatin sponge (Gelfoam?) and characterized the resultant constructs. Results showed that PDCA-Gelfoam could stimulate pro-angiogenic signalling in infiltrating cells and accelerate vascular infiltration in rats, demonstrating that our vascularization strategy is viable.

As other studies have suggested that PHIs may have applications in bone regeneration, we performed a preliminary study to assess various PHIs? effects on osteoblasts. Results showed that while PHIs could stimulate pro-angiogenic signalling, they also reduced collagen production and had differential effects on mineralization. Our results suggest that both the type of PHI and the duration of treatment are critical determinants of their utility in bone regeneration.