Dose Effect of Dual Delivery of Vascular Endothelial Growth Factor and Bone Morphogenetic Protein-2 on Bone Regeneration in a Rat Critical-size Defect Model

Overview

Journal Tissue Eng Part A

Specialties Anatomy & Histology
Biomedical Engineering
Biotechnology

Date 2009 Mar 3

PMID 19249918

Citations 95

Authors

Simon Young

Zarana S Patel

James D Kretlow

Matthew B Murphy

Paschalia M Mountziaris

L Scott Baggett

Hiroki Ueda

Yasuhiko Tabata

John A Jansen

Mark Wong

Antonios G Mikos

Affiliations

Soon will be listed here.

Abstract

The dose effect of dual delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) on bone regeneration was investigated in a rat cranial critical-size defect (CSD). It was hypothesized that decreasing amounts of BMP-2 would result in a dose-dependent decrease in bone formation, and that this reduction in bone formation could be reversed by adding increasing amounts of VEGF. In vitro release kinetics of VEGF or BMP-2 were examined over 28 days. Next, scaffolds were implanted within a rat cranial CSD containing different combinations of both BMP-2 and VEGF. At 12 weeks, samples were analyzed using microcomputed tomography and histology. In vitro, VEGF and BMP-2 exhibited burst release in the first 24 h followed by a significant decrease in release rate over 27 days. Overall, BMP-2 had a more sustained release versus VEGF. An in vivo dose-dependent decrease in percentage of bone fill (PBF) was observed for BMP-2. The addition of VEGF was unable to reverse this decrease in PBF, although improvements in the number of bridged defects did occur in some groups. This suggests that for this particular model simultaneous release of BMP-2 and VEGF does not increase bone formation over BMP-2 alone at 12 weeks.

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