The action of microbial collagenases in dentinal matrix degradation in root caries and potential strategies for its management: a comprehensive state-of-the-art review.

Conventional views associate microbial biofilm with demineralization in root caries (RC) onset, while research on their collagenases role in the breakdown of collagen matrix has been sporadically developed, primarily in vitro. Recent discoveries, however, reveal proteolytic bacteria enrichment, specially Porphyromonas and other periodontitis-associated bacteria in subgingivally extended lesions, suggesting a potential role in RC by the catabolism of dentin organic matrix. Moreover, genes encoding proteases and bacterial collagenases, including the U32 family collagenases, were found to be overexpressed in both coronal and root dentinal caries. Despite these advancements, to prove microbial collagenolytic proteases' definitive role in RC remains a significant challenge. A more thorough investigation is warranted to explore the potential of anti-collagenolytic agents in modulating biofilm metabolic processes or inhibiting/reducing the size of RC lesions. Prospective treatments targeting collagenases and promoting biomodification through collagen fibril cross-linking show promise for RC prevention and management. However, these studies are currently in the in vitro phase, necessitating additional research to translate findings into clinical applications. This is a comprehensive state-of-the-art review aimed to explore contributing factors to the formation of RC lesions, particularly focusing on collagen degradation in root tissues by microbial collagenases.

Presence of host and bacterial-derived collagenolytic proteases in carious dentin: a systematic review of ex vivo studies.

Introduction and aim: The presence of host collagenases in the degradation of the protein matrix at later stages of carious dentin lesions development, as well as the potential involvement of bacterial collagenases, have been suggested but lack conclusive evidence. This study aims to conduct a systematic review to comprehensively assess the profile of host and bacterial-derived collagenolytic proteases in both root and coronal dentin carious lesions. Methods: The search was performed in eight databases and the grey literature. Studies evaluating ex vivo dentin, extracted teeth, or biofilms from natural caries lesions were included. The methodological quality of studies was assessed using the Joanna Briggs Institute tool. Synthesis of the results and the certainty of evidence were performed following the Synthesis without Meta-analysis (SWiM) checklist and GRADE approach for narrative synthesis, respectively. Results: From 935 recovered articles, 18 were included. Although the evidence was very uncertain, it was possible to suggest that 1) MMP-2, MMP-9, MMP-13, and CT-B may be increased in carious dentin when compared to sound dentin; 2) there is no difference in MMP-2 presence, while MMP-13 may be increased in root when compared to coronal carious dentin; 3) there is no difference of MMP-2 and MMP-9 expression/activity before and after cavity sealing; 4) MMP-8 may be increased in the dentin before cavity sealing compared to dentin after cavity sealing; 5) there is no difference of MMP-20 in irradiated vs. non-irradiated carious dentin. MMP-20 probably reduces in carious outer dentin when compared to carious inner dentin (moderate certainty). Genes encoding bacterial collagenolytic proteases and protein-degrading bacteria were detected in coronal and root carious lesions. Conclusion: Trends in the direction of the effect were observed for some collagenolytic proteases in carious dentin, which may represent a potential target for the development of new treatments. (Protocol register-PROSPERO: CRD42020213141).

Sustainable multifunctional phenolic lipids as potential therapeutics in Dentistry.

Phenolic lipids components of the cashew nutshell liquid (CNSL) have molecular structures capable of chemical signalling that regulate gene expression, metabolism and inflammation. This study sets out to assess how CNSL derivatives impact oral bacteria, from an antibacterial and anti-collagenolytic perspective, as well as its biocompatibility with dental pulp stem cells. Two hemi-synthetic saturated CNSL derivative compounds were selected (LDT11-Anacardic Acids-derivative and LDT409-cardanol-derivative). Bacteriostatic activity was tested against Streptococcus mutans and Veillonella parvula. Antimicrobial capacity against preformed S. mutans biofilms was investigated using a collagen-coated Calgary Biofilm Device and confocal microscopy. Clostridium histolyticum, P. gingivalis and S. mutans biofilms were used to assess anti-collagenolytic activity. Biocompatibility with human dental pulp stromal cells (HDPSCs) was investigated (MTT for viability proportion, LDH assays for cell death rate). LDTs inhibited the bacterial growth, as well as partially inhibited bacterial collagenases in concentrations higher than 5 µg/mL. Dose-response rates of biofilm cell death was observed (LDT11 at 20, 50, 100 µg/mL = 1.0 ± 0.4, 0.7 ± 0.3, 0.6 ± 0.03, respectively). Maximum cytotoxicity was 30%. After 1 week, LDT409 had no HDPSCs death. HDPSCs viability was decreased after 24 h of treatment with LDT11 and LDT409, but recovered at 72 h and showed a massive increase in viability and proliferation after 1 week. LDTs treatment was associated with odontoblast-like morphology. In conclusion, LDT11 multifunctionality and biocompatibility, stimulating dental pulp stem cells proliferation and differentiation, indicates a potential as a bio-based dental material for regenerative Dentistry. Its potential as a bacterial collagenases inhibitor to reduce collagen degradation in root/dentinal caries can be further explored.