Abstract

The control of inflammation and infection is crucial for periodontal wound healing and regeneration. M101, an oxygen carrier derived from Arenicola marina, was tested for its anti-inflammatory and anti-infectious potential based on its anti-oxidative and tissue oxygenation properties. In vitro, no cytotoxicity was observed in oral epithelial cells (EC) treated with M101. M101 (1 g/L) reduced significantly the gene expression of pro-inflammatory markers such as TNF-α, NF-κΒ and RANKL in P. gingivalis-LPS stimulated and P. gingivalis-infected EC. The proteome array revealed significant down-regulation of pro-inflammatory cytokines (IL-1β and IL-8) and chemokine ligands (RANTES and IP-10), and upregulation of pro-healing mediators (PDGF-BB, TGF-β1, IL-10, IL-2, IL-4, IL-11 and IL-15) and, extracellular and immune modulators (TIMP-2, M-CSF and ICAM-1). M101 significantly increased the gene expression of Resolvin-E1 receptor. Furthermore, M101 treatment reduced P. gingivalis biofilm growth over glass surface, observed with live/dead analysis and by decreased P. gingivalis 16 s rRNA expression (51.7%) (p < 0.05). In mice, M101 reduced the clinical abscess size (50.2%) in P. gingivalis-induced calvarial lesion concomitant with a decreased inflammatory score evaluated through histomorphometric analysis, thus, improving soft tissue and bone healing response. Therefore, M101 may be a novel therapeutic agent that could be beneficial in the management of P. gingivalis associated diseases.

Highlights

  • The control of inflammation and infection is crucial for periodontal wound healing and regeneration

  • The control of inflammation and infection is crucial for achieving an optimal wound healing response in the context of periodontitis management

  • M101, an oxygen transporter derived from Arenicola marina, was tested for its anti-inflammatory and anti-infectious potential based on its anti-oxidative and tissue oxygenation properties

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Summary

Introduction

The control of inflammation and infection is crucial for periodontal wound healing and regeneration. Severe periodontitis has been ranked as the 6th most prevalent disease worldwide affecting around 743 million p­ eople[2] It has been associated with reduced quality of life and is considered as one of the main causes of tooth ­loss[3]. Initiation of periodontitis is associated with the development of oral biofilm over teeth and gums resulting in low-grade inflammation with no evident clinical signs Failure to disrupt this biofilm actuates a change in oral microenvironment, thereby shifting the balance from symbiotic to a predominantly dysbiotic microbial flora, inducing an exacerbated inflammatory ­response[5,6]. Several natural and synthetic compounds, and novel combinations of drugs with local drug delivery scaffolds have been developed and tested to improve treatment outcomes with tissue-targeted drug ­delivery[24,25,26,27,28,29]

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