Effects of VEGF-loaded chitosan coatings

Abstract

Vascular endothelial growth factor (VEGF) is a powerful growth factor that promotes vascularization as well as osteoblastic differentiation and bone regeneration, all of which are key processes in the osseointegration of dental implants. Strategies to increase vascularization through delivery of VEGF may improve osseointegration, especially in patients with reduced bone healing potential. The aim of this study was to determine the potential of chitosan coatings on titanium to deliver VEGF and to support growth and matrix production of osteoblastic cells in vitro. Chitosan was chemically bonded to titanium coupons via silane-glutaraldehyde linker molecules and loaded with 0, 20, 50, or 100 ng of VEGF. Protein was released during a three day period with around 75% of VEGF (4.44, 11.37, and 22.10 ng/mL/cm(2) from the 20, 50, and 100 ng loaded levels, respectively) released during the first 12 h, and 90-95% of the VEGF released from the coatings by day 3. Saos-2 bone cells continued to proliferate over the 28-day period on the VEGF-loaded chitosan coatings in contrast to cells seeded on uncoated titanium, which plateaued after 14 days. Cells on uncoated titanium exhibited a peak in alkaline phosphatase expression at approximately 14 days, concomitant with the plateau in growth. While osteoblast-like cells on all chitosan coatings exhibited up to a 2-fold enhancement of the alkaline phosphatase activity and 10-fold increase in calcium deposition compared to uncoated controls, the incorporation of VEGF into the coatings did not enhance osteoblast matrix production over plain chitosan coatings throughout this study.

Keywords: VEGF; chitosan; mineralization; osseointegration; titanium.