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GUEST EDITORIAL
Year : 2014  |  Volume : 6  |  Issue : 1  |  Page : 3-5

What is the future of periodontal regeneration?


Vice President, Clinical and Translational Research, Forsyth Institute, Cambridge, MA, USA

Date of Web Publication18-Aug-2014

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DOI: 10.4103/2231-0754.139081

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How to cite this article:
Van Dyke TE. What is the future of periodontal regeneration?. J Int Clin Dent Res Organ 2014;6:3-5

How to cite this URL:
Van Dyke TE. What is the future of periodontal regeneration?. J Int Clin Dent Res Organ [serial online] 2014 [cited 2019 Jul 23];6:3-5. Available from: http://www.jicdro.org/text.asp?2014/6/1/3/139081

Periodontitis is an inflammatory disease of bacterial etiology that results in host-mediated destruction of the supporting tissues of the teeth, including connective tissue attachment and bone. Clinically, periodontitis is difficult to treat with a high rate of recurrence. Regeneration of hard and soft tissues lost to disease is limited and not predictable. [24],[27],[33] The classic tissue engineering triad (cells, mediators, and scaffold) is missing a critical component - the control of inflammation. Tissue regeneration cannot occur in the presence of uncontrolled local inflammation.

The ideal outcome of acute inflammation is its complete resolution. [28] It is now widely appreciated that uncontrolled acute inflammation can lead to tissue injury, chronic inflammation, tissue scarring, and fibrosis. [30],[43] In the face of uncontrolled host defense mechanisms, tissue engineering, regeneration, and reconstruction of both diseased and injured oral and craniofacial tissues are significantly hampered. [22],[50] In periodontal disease (and in any contaminated oral or craniofacial traumatic wound), an uncontrolled inflammatory response causes neutrophil (PMN)-mediated tissue injury which in turn leads to irreversible bone loss. Periodontal infections are a major public health concern and financial burden. [22],[26],[50] PMN actions are important for protection in microbial host defense, but chronic PMN activity releases noxious materials leading to injury and loss of organ function. [5],[29] In periodontitis, tissue destruction results from a combination of sustained microbial challenge and a failure of endogenous resolution of inflammation. [11],[47] New data revealed that endogenous control of inflammation directly affects bone healing and regeneration. Mediators of resolution of inflammation have actions beyond control of PMN function; they exhibit receptor-mediated control of osteoclast and osteoblast function in wound healing and bone regeneration.


   Programmed resolution of inflammation Top


Specific functionally distinct profiles of eicosanoid-derived lipid mediators (LM) have a major impact on wound healing and tissue regeneration. Pro-inflammatory LM profiles include the classic eicosanoids, prostaglandins (PG), and leukotrienes (LT), whereas the new LM profiles include lipoxins (LX) from arachidonic acid and the novel resolvins (Rv) and protectins from the omega-3 essential fatty acids EPA and DHA, respectively. Together, these local mediators constitute a new genus of endogenous anti-inflammatory and pro-resolving compounds that have proven to be very potent in treating several inflammation-associated models of human disease (Serhan and Chiang 2008). [20],[25],[37],[44] These include arthritis, [25] colitis, [2] peritonitis, [42],[45] asthma, [1],[19],[20] dermatitis, [31] infantile eczema, [51] diabetic wounds, [44],[46] and retinopathies. [6],[23] Resolvin, RvE1 (5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid) reduces oral inflammation in rabbit periodontitis [14] and regenerates associated bone loss. [13]

In health, acute inflammation either is "self-limited" (completely resolving with no scarring), progresses to an abscess, or becomes chronic. [7] Excessive accumulation of PMN within tissues plays a critical role in the pathogenesis of periodontal disease [18] and limits success of both tissue engineering and regeneration. [8],[22] It is likely that the dysregulated host response, recognized as chronic human diseases such as periodontitis, Crohn's disease, and even certain cancers, [48] in part, reflects diminished local biosynthesis of "resolving signals" or their lack of production. [35]

Acute inflammation is resolved when the initial injury is limited or short-lived, and the injurious stimuli are successfully neutralized, enabling the site to return to normal. [7] Steps in resolution of inflammations are:

  1. Cessation of leukocyte infiltration;
  2. Vascular permeability/edema returns to normal;
  3. PMN death (mostly via apoptosis);
  4. Non-phlogistic infiltration of monocyte/macrophages, and
  5. Macrophage removal of apoptotic PMN, foreign agents (bacteria), and necrotic debris from the site. [12],[32]


Although the concept of resolution of disease is well appreciated by clinicians, [7],[28] resolution of tissue inflammation was considered a passive process. Manipulation of resolution agonist actions offers many opportunities for targeting novel therapeutic strategies [9],[29] and insight into disease pathogenesis. [35] LX and Rv can control inflammation by stimulating resolution without immune suppression.

Importantly, new discoveries reveal that the actions of resolution agonists (LX, Rv) are not limited to inflammatory cells; they play key roles in clearance of infection, [13] and they have both direct and indirect actions on bone cells in tissue regeneration and bone remodeling. [16] These observations bring us closer to an understanding of the role of resolution in healing of chronic infected wounds such as periodontitis and regeneration of hard and soft tissues lost to disease. Indeed, translation of promising experiments in animals to the clinic is a near-term goal for advancing the science of periodontal regeneration.

 
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   Authors Top



About the AuthorThomas Van Dyke, D.M.D., Ph.D., is Vice President for Clinical and Translational Research, and Chair, Department of Periodontology at the Forsyth Institute in Cambridge, MA. He received his D.D.S. (1973) from Case Western Reserve University; M.S. (1979) from SUNY at Buffalo in Oral Sciences; Periodontics Certificate (1980) from SUNY at Buffalo, and his Ph.D. (1982) from SUNY at Buffalo in Oral Biology. Dr. Van Dyke received the Balint Orban Memorial Prize for Research in Periodontology (1981). He is a Diplomate of the American Board of Periodontology (1989), and he received the IADR Award for Basic Research in Periodontology in 2001, the Norton Ross Award for Excellence in Clinical Research in 2002, and the William J. Gies Periodontology Award in 2008. He serves on the editorial boards of Infection and Immunity, Journal of Periodontology, Journal of Periodontal Research, among others, and he has edited two volumes of Periodontology 2000. He served as President of the International Association of Periodontology (1997-1999). Dr. Van Dyke has published 250+ original articles, and numerous abstracts and book chapters. He is a member of the American/International Association of Dental Research; American Academy of Periodontology; International Association of Periodontology, American Association for the Advancement of Science, American Society of Microbiology, IADR Periodontal Research Group, American Dental Association, and Northeast Periodontal Society. His research interests are the structural and functional relationship of abnormalities of the inflammatory process with focus on phagocytic cells and microorganisms, in the etiology and pathogenesis of periodontal diseases; host susceptibility to specific periodontal infections. He is best known for his work on the pathogenesis of juvenile periodontal diseases, resolution of inflammation in neutrophil biology, and clinical research.




 

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