Regenerative Medicine for Periodontal and Peri-implant Diseases

Abstract

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions.

Keywords: 3D printing; alveolar bone; gene therapy; growth factors; regeneration; tissue engineering.

Figure 1.

Influencing factors for periodontal regenerative medicine. Periodontal diseases can result in significant damage to the periodontal structures. Following resolution of etiologic factors and controlling host response/inflammation, periodontal regeneration is necessary to restore health. Periodontal regeneration can be achieved clinically through the use of cell therapy, biologics, and biomaterial scaffolds in the context of an adequate blood supply.

Figure 2.

Approaches for regenerating periodontal and peri-implant supporting tissues. Guided tissue regeneration involving bone substitutes and barrier membrane and bone fill can be used for tissue regeneration in periodontitis defects and peri-implantitis defects. Development of implant sites after tooth extraction can be obtained in either a 1- or 2-stage bone augmentation process.

Figure 3.

Gene therapeutics for tissue engineering/regenerative medicine. Gene therapy includes several steps: consider the gene therapy vector, a tissue growth factor, the method of delivery, the target cells, and finally, the local effect. 3D, 3-dimensional; AAV, adeno-associated virus; BMP, bone morphogenetic protein; FGF, fibroblast growth factor; PDGF, platelet-derived growth factor.

Figure 4.

Design of a customized scaffold using 3-dimensional (3D) printing. (A) 3D printing has been used to design a scaffold consisting of a periodontal ligament (PDL) portion and a bone portion. This was further modified to improve the fiber-guiding potential as well as the direction of the PDL to mimic the topography of the different kinds of fibers in the PDL (first row). Digitalized cross-sectional view of a 3D-reconstructed image. Longitudinal cross-section image showed pore morphologies at coronal and apical portions. Scanning electron microscopy image providing longitudinal pores produced by a freeze-casting method. Adapted from Park et al. (2010), Park et al. (2012), and Park et al. (2014) with permission. (B) 3D printing using polycaprolactone was made to fit the periosseous defect based on the patient’s cone beam computed tomography scan. Adapted from Rasperini et al. (2015) with permission.