Abstract

Background: Periodontal disease is a chronic inflammatory condition that affects supporting tissues around teeth, resulting in periodontal tissue breakdown. If left untreated, periodontal disease could have serious consequences; this condition is in fact considered as the primary cause of tooth loss. Being highly prevalent among adults, periodontal disease treatment is receiving increased attention from researchers and clinicians. When this condition occurs around dental implants, the disease is termed peri-implantitis. Periodontal regeneration aims at restoring the destroyed attachment apparatus, in order to improve tooth stability and thus reduce disease progression and subsequent periodontal tissue breakdown. Although many biomaterials have been developed to promote periodontal regeneration, they still have their own set of disadvantages. As a result, regenerative medicine has been employed in the periodontal field, not only to overcome the drawbacks of the conventional biomaterials but also to ensure more predictable regenerative outcomes with minimal complications. Regenerative medicine is considered a part of the research field called tissue engineering/regenerative medicine (TE/RM), a translational field combining cell therapy, biomaterial, biomedical engineering and genetics all with the aim to replace and restore tissues or organs to their normal function using in vitro models for in vivo regeneration. In a tissue, cells are responding to different micro-environmental cues and signaling molecules, these biological factors influence cell differentiation, migration and cell responses. A central part of TE/RM therapy is introducing drugs, genetic materials or proteins to induce specific cellular responses in the cells at the site of tissue repair in order to enhance and improve tissue regeneration. In this review, we present the state of art of gene therapy in the applications of periodontal tissue and peri-implant regeneration. Purpose: We aim herein to review the currently available methods for gene therapy, which include the utilization of viral/non-viral vectors and how they might serve as therapeutic potentials in regenerative medicine for periodontal and peri-implant tissues.

Highlights

  • Periodontal disease is a common oral disease in humans [1]. It is characterized by a chronic inflammatory reaction of periodontal tissues that leads to the destruction of the attachment apparatus of the tooth, including alveolar bone, cementum, and the periodontal ligament (PDL) [2]

  • The findings of this study demonstrated that adenovirus vector (AV)/platelet-derived growth factors (PDGFs)-B gene delivery displays sustained signal transduction effects in human gingival fibroblasts [43]

  • The results of this study showed that AAV2/1-TNF receptor-immunoglobulin Fc (TNFR):Fc led to potent inhibition of periodontal disease progression [46]

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Summary

Periodontitis and Peri-Implantitis

Periodontal disease is a common oral disease in humans [1] It is characterized by a chronic inflammatory reaction of periodontal tissues that leads to the destruction of the attachment apparatus of the tooth, including alveolar bone, cementum, and the periodontal ligament (PDL) [2]. Tissue engineering/regenerative medicine (TE/RM) is an established research field combining cell therapy, biomaterials, biomedical engineering and genetics all with the aim “to stimulate regeneration of tissues and organs by either implanting biomaterials for in vivo regeneration or by constructing substitutes in vitro” [9]. The primary goal of regenerative periodontal bioengineering is “to promote endogenous repair mechanisms and functional regeneration through the delivery of key growth factors (GFs) or cytokines that stimulate host cells to invade a tissue defect and direct robust extra cellular matrix synthesis in vivo” [13]. Periodontal tissue engineering encloses three approaches: (1) Protein-based therapy (delivery of GFs), (2) cell-based therapy (delivery of stem cells), (3) gene-based therapy (delivery of genes) [12]

Rationale of Gene Therapy for Periodontal Tissue Engineering
Definition and History
General Principles of Gene Therapy
DNA Versus RNA Delivery
Delivery Vehicles
Viral Vectors
Non-Viral Vectors
Inducible Systems for Viral Delivery
Exosomes
Route of Gene Delivery
Lentiviral Vectors
Bubble Liposomes and Ultrasound for Gene Delivery
Future Perspectives
Conclusions

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