Inflammatory and bone remodelling related biomarkers following periodontal transplantation of the tissue engineered biocomplex.

OBJECTIVES: To assess gingival crevicular fluid (GCF) levels of inflammatory and bone remodelling related biomarkers following transplantation of a tissue-engineered biocomplex into intrabony defects at several time-points over 12-months. MATERIALS AND METHODS: Group-A (n = 9) received the Minimal Access Flap (MAF) surgical technique combined with a biocomplex of autologous clinical-grade alveolar bone-marrow mesenchymal stem cells in collagen scaffolds enriched with an autologous fibrin/platelet lysate (aFPL). Group-B (n = 10) received the MAF surgery, with collagen scaffolds enriched with aFPL and Group-C (n = 8) received the MAF surgery alone. GCF was collected from the osseous defects of subjects via paper strips/30 sec at baseline, 6-weeks, 3-, 6-, 9-, 12-months post-surgery. Levels of inflammatory and bone remodelling-related biomarkers in GCF were determined by ELISA. RESULTS: Group-A demonstrated significantly higher GCF levels of BMP-7 at 6-9 months than baseline, with gradually decreasing levels of pro-inflammatory and pro-osteoclastogenic markers (TNF-α, RANKL) over the study-period; and an overall decrease in the RANKL/OPG ratio at 9-12 months than baseline (all p < 0.001). In comparison, only modest interim changes were observed in Groups-B and -C. CONCLUSIONS: At the protein level, the approach of MAF and biocomplex transplantation provided greater tissue regeneration potential as cell-based therapy appeared to modulate inflammation and bone remodelling in residual periodontal defects. CLINICAL RELEVANCE: Transplantation of a tissue engineered construct into periodontal intrabony defects demonstrated a biochemical pattern for inflammatory control and tissue regeneration over 12-months compared to the control treatments. Understanding the biological healing events of stem cell transplantation may facilitate the design of novel treatment strategies. CLINICAL DATABASE REGISTRATION: ClinicalTrials.gov ID: NCT02449005.

Microbial-stem cell interactions in periodontal disease.

Periodontitis is initiated by hyper-inflammatory responses in the periodontal tissues that generate dysbiotic ecological changes within the microbial communities. As a result, supportive tissues of the tooth are damaged and periodontal attachment is lost. Gingival recession, formation of periodontal pockets with the presence of bleeding, and often suppuration and/or tooth mobility are evident upon clinical examination. These changes may ultimately lead to tooth loss. Mesenchymal stem cells (MSCs) are implicated in controlling periodontal disease progression and have been shown to play a key role in periodontal tissue homeostasis and regeneration. Evidence shows that MSCs interact with subgingival microorganisms and their by-products and modulate the activity of immune cells by either paracrine mechanisms or direct cell-to-cell contact. The aim of this review is to reveal the interactions that take place between microbes and in particular periodontal pathogens and MSCs in order to understand the factors and mechanisms that modulate the regenerative capacity of periodontal tissues and the ability of the host to defend against putative pathogens. The clinical implications of these interactions in terms of anti-inflammatory and paracrine responses of MSCs, anti-microbial properties and alterations in function including their regenerative potential are critically discussed based on literature findings. In addition, future directions to design periodontal research models and study ex vivo the microbial-stem cell interactions are introduced.