Current concepts in periodontal bioengineering

Abstract

Repair of tooth supporting alveolar bone defects caused by periodontal and peri-implant tissue destruction is a major goal of reconstructive therapy. Oral and craniofacial tissue engineering has been achieved with limited success by the utilization of a variety of approaches such as cell-occlusive barrier membranes, bone substitutes and autogenous block grafting techniques. Signaling molecules such as growth factors have been used to restore lost tooth support because of damage by periodontal disease or trauma. This paper will review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Several different polymer delivery systems that aid in the targeting of proteins, genes and cells to periodontal and peri-implant defects will be highlighted. Results from preclinical and clinical trials will be reviewed using the topical application of bone morphogenetic proteins (BMP-2 and BMP-7) and platelet-derived growth factor-BB (PDGF) for periodontal and peri-implant regeneration. The paper concludes with recent research on the use of ex vivo and in vivo gene delivery strategies via gene therapy vectors encoding growth promoting and inhibiting molecules (PDGF, BMP, noggin and others) to regenerate periodontal structures including bone, periodontal ligament and cementum.

Fig. 1

Schematic representation of critical elements required in periodontal tissue engineering. Reconstruction of lost periodontal tissue requires the combination of cells, scaffolds, signaling molecules, and a blood supply. A limiting factor in the achievement of periodontal regeneration is the presence of microbial pathogens that contaminate periodontal wounds and reside on tooth surfaces as plaque-associated biofilms.

Fig. 2

Cell therapy for periodontal tissue engineering: (A) SEM image of poly-lactide-co-glycolide acid (PLGA) scaffold and seeded cells into scaffolds; (B) tissue engineering approach for ectopic mineralization in mice, cells are expanded in culture prior to being seeded into the scaffolds for implantation; (C) periodontal ligament cells (PDL) do not promote mineralization in vivo, while cementoblasts show mineralization, 20× magnification.

Fig. 3

Bone regeneration via cartilage intermediate: recombinant adenovirus encoding murine BMP-7 (Ad-BMP-7) promoting periodontal bone regeneration via a cartilage intermediate evaluated after 10 and 21 days of ex vivo gene transfer to periodontal wounds. After 10 days, specimens demonstrated islands of cartilage and chondroblast-like cells. After 21 days, specimens demonstrated woven bone and mature cartilage intimately associated with newly formed bone. The bottom panel shows an image of chondroblast-like cells and cartilaginous matrix surrounded by new bone adjacent to the tooth surface. H&E and toluidine blue staining at 10× magnification, high power image at 20× magnification. Reprinted in part from Jin et al. (27), with permission.

Fig. 4

Gene delivery strategies for tissue engineering: ex vivo approach, tissue biopsy from donor site have cells isolated and expanded in cell culture. Vectors (e.g. adenovirus or plasmids) are used to transduce the cells in vitro. Cells are then seeded onto biodegradable scaffolds delivered to the wound site. In the in vivo approach, genes are directly delivered to the wounds using (in this example) collagen gel as a carrier.