Background-The reconstruction of lost periodontal support including bone, ligament, and cementum is a major goal of therapy. Bone morphogenetic proteins (BMPs) have shown much potential in the regeneration of the periodontium. Limitations of BMP administration to periodontal lesions include need for high-dose bolus delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene transfer offers promise as an alternative treatment strategy to deliver BMPs to periodontal tissues.

Platelet-derived growth factor (PDGF) exerts potent effects on wound healing including the regeneration of tooth-supporting structures. Limitations of topical protein delivery to periodontal osseous defects include transient biological activity and the bioavailability of PDGF at the wound site. The objective of this investigation was to determine the feasibility of in vivo PDGF-B gene transfer to stimulate periodontal tissue regeneration in large tooth-associated alveolar bone defects in rats. Periodontal lesions (0.3 x 0.2 cm in size) were treated with a 2.6% collagen matrix alone or a matrix containing adenoviruses encoding luciferase (control), a dominant negative mutant of PDGF-A (PDGF-1308), or PDGF-B. Block biopsies were harvested at 3, 7, and 14 days post-gene delivery and descriptive histology and histomorphometric analyses were performed. The defects treated with Ad-PDGF-B demonstrated greater proliferating cell nuclear antigen positively stained cells and strong evidence of bone and cementum regeneration beyond that of Ad-luciferase and Ad-PDGF-1308 groups. Quantitative image analysis showed a nearly fourfold increase in bridging bone and sixfold increase in tooth-lining cemental repair in the Ad-PDGF-B-treated sites compared to lesions treated with Ad-luciferase or collagen matrix alone, which showed limited hard tissue neogenesis. In addition, the Xenogen In Vivo Imaging System revealed sustained and localized gene expression of the luciferase reporter at the periodontal lesions for up to 21 days after gene transfer. These results indicate that in vivo direct gene transfer of PDGF-B stimulates alveolar bone and cementum regeneration in large periodontal defects. Gene therapy utilizing PDGF-B may offer the potential for periodontal tissue engineering applications.

Genetic polymorphism of IL-1 genes in these two loci may not be useful in predicting the severity of periodontal disease in the Thai ethnic group.

Destruction of tooth support due to the chronic inflammatory disease 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 because of 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. The objective of this study was to test the effect of PDGF-A and PDGF-B gene transfer to human gingival fibroblasts (HGFs) on ex vivo repair in three-dimensional collagen lattices. HGFs were transduced with adenovirus encoding PDGF-A and PDGF-B genes. Defect fill of bilayer collagen gels was measured by image analysis of cell repopulation into the gingival defects. The modulation of gene expression at the defect site and periphery was measured by RT-PCR during a 10-day time course after gene delivery. The results demonstrated that PDGF-B gene transfer stimulated potent (>4-fold) increases in cell repopulation and defect fill above that of PDGF-A and corresponding controls. PDGF-A and PDGF-B gene expression was maintained for at least 10 days. PDGF gene transfer upregulated the expression of phosphatidylinosital 3-kinase and integrin alpha5 subunit at 5 days after adenovirus transduction. These results suggest that PDGF gene transfer has potential for periodontal soft tissue-engineering applications.

Repair of tooth-supporting structures destroyed by the chronic inflammatory disease periodontitis is a major goal of oral therapy. The field of tissue engineering combines materials science and biology to repair tissues and organs. Periodontal tissue engineering has been achieved with limited success by the utilization of guiding tissue (cell occlusive) membranes and bone grafting techniques. Over the past decade investigators have begun to utilize signaling molecules such as growth factors to restore lost tooth support due to periodontitis, the most common bone disease affecting humans. This review will provide information on the status of growth factor therapies being applied in periodontology to treat advanced alveolar bone loss.