Gene therapeutics for periodontal regenerative medicine

Abstract

There has been significant advancement in the field of periodontal tissue engineering over the past decade for the repair of tooth-supporting structures. Although encouraging results for periodontal tissue regeneration have been found in numerous clinical investigations using recombinant growth factors, limitations exist with topical protein delivery. Newer approaches seek to develop methodologies that optimize growth factor targeting to maximize the therapeutic outcome of periodontal regenerative procedures. Genetic approaches in periodontal tissue engineering show early progress in achieving delivery of growth factor genes, such as platelet-derived growth factor or bone morphogenetic protein, to periodontal lesions. Ongoing investigations in ex vivo and in vivo gene transfer to periodontia seek to examine the extent of the potential effects in stimulating periodontal tissue engineering.

Fig. 1

Approaches for regenerating tooth-supporting structures. (A) Guided tissue regeneration uses a cell occlusive barrier membrane to restore periodontal tissues. (B) Alternatively, an example of gene therapy uses vector-encoding growth factors aimed at stimulating the regeneration of host cells derived from the periodontium.

Fig. 2

The current paradigm of gene therapy used in periodontal tissue engineering. Approaches consider (A) methods of delivery, (B) gene therapy vector, (C) tissue growth factor, (D) cellular target receptors, and (E) local effect. The choice of delivery method, DNA vector, and growth factor should maximize expected effect, minimize patient risk, and reflect the characteristics of the wound site.

Fig. 3

Gene delivery approaches for periodontal tissue engineering. (A) Ex vivo gene delivery involves the harvesting of tissue biopsies, expansion of cell populations, genetic manipulations of cells, and subsequent transplantation to periodontal osseous defects. (B) The in vivo gene transfer approach involves the direct delivery of growth factor transgenes to the periodontal osseous defects.

Fig. 4

In vivo gene transfer of PDGF-B stimulates periodontal tissue regeneration. Histologic microphotographs of periodontal alveolar bone defects treated for 14 days after gene delivery of Ad/PDGF-B, Ad/PDGF-1308, or vector alone. (A, C, E, original magnification ×40; B, D, F, original magnification ×200.) Brackets in the low-power (×40) slides indicate alveolar bone wound edges, with no significant differences between the sizes of the defects based on histomorphometric analyses. Limited alveolar bone formation occurred in the Ad/PDGF-1308 and vector alone defects, whereas significant bone bridging was noted most extensively in sites treated with Ad/PDGF-B (red dashed line). (F) A thin layer of newly formed cementum (black arrows) was observed only in the Ad/PDGF-B–treated defects. More vascularization (blue arrows) was seen in the periodontal ligament region of the Ad/PDGF-B–treated lesions. Asterisks indicate the collagen carrier. (Adapted from Jin Q, Anusaksathien O, Webb SA, et al. Engineering of tooth-supporting structures by delivery of PDGF gene therapy vectors. Mol Ther 2004;9(4):522; with permission.)