Delivery of PDGF Genes Stimulates Gingival Wound Repair

Introduction: Destruction of tooth supporting structure due to periodontitis is a major cause of tooth loss. There are limitations with available treatment options to tissue engineer soft tissue periodontal defects. The exogenous application of growth factors (GFs) such as platelet-derived growth factor (PDGF) has shown promise to enhance oral and periodontal tissue regeneration. However, the topical administration of GFs has not led to clinically significant improvements in tissue regeneration due to problems in maintaining therapeutic protein levels at the defect site. The utilization of PDGF gene transfer may circumvent many of the limitations with protein delivery to soft tissue wounds. Objectives: The objective of this study was to test the effect of PDGF-A and -B gene transfer to human gingival fibroblasts (HGFs) on in vitro wound repair in three-dimensional collagen lattices. Methods: HGFs were transduced with adenoviruses encoding PDGF-A or -B genes. Wound closure of bilayer collagen gels was measured using image analysis of cell migration and proliferation into the gingival wound defects. The data were analyzed using one way ANOVA and Fisher's PLSD to measure the differences among groups. The modulation of gene expression at the wound site and periphery was assessed using RT-PCR during a 10-day timecourse following gene delivery. Results: The results demonstrated that PDGF-B gene transfer stimulated potent (> 4 fold) increases in cell migration, proliferation and wound closure above that of PDGF-A and corresponding controls (p<0.001). PDGF-A and PDGF-B gene expression was maintained in this model for at least 10 days. PDGF-B gene transfer upregulated the expression of PI3 kinase and integrin alpha 5 subunit at 5 days following adenovirus transduction. Conclusion: These results suggest that PDGF-B gene transfer has potential for periodontal soft tissue engineering applications. Funded by NIH/NIDCR grants DE 11960 and 13397 and by a University of Michigan Rackham Faculty Award.