Platelet analogues in periodontal regeneration: A narrative review

Platelet analogues (PA; platelet rich plasma and platelet rich fibrin) are autologous bioactive compounds that have a wide range of medical and dental applications, including periodontal, maxillofacial, Plastic surgery and sports medicine. The aim of these technologies is to collect all the constituents of a patient's blood sample so that they can be used to promote tissue regeneration and improve healing. Since 1954, PA has come a long way. Periodontology and implant dentistry have both benefited from the use of PAs. However, the non-standard preparation technique, processing time, transfer of concentrates, centrifugation temperature, vibration, etc. are all variables that contribute to the various results described in the literature. This study will retrace the evolution of PAs, their preparation procedures, their clinical and technological characteristics and their uses.

Salivary Exosomes: From Waste to Promising Periodontitis Treatment

Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.

Comprehensive analysis of the long noncoding RNA-associated competitive endogenous RNA network in the osteogenic differentiation of periodontal ligament stem cells

Backgroud The mechanism implicated in the osteogenesis of human periodontal ligament stem cells (PDLSCs) has been investigated for years. Previous genomics data analyses showed that long noncoding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) have significant expression differences between induced and control human PDLSCs. Competing for endogenous RNAs (ceRNA), as a widely studied mechanism in regenerative medicine, while rarely reported in periodontal regeneration. The key lncRNAs and their ceRNA network might provide new insights into molecular therapies of periodontal regeneration based on PDLSCs. Results Two networks reflecting the relationships among differentially expressed RNAs were constructed. One ceRNA network was composed of 6 upregulated lncRNAs, 280 upregulated mRNAs, and 18 downregulated miRNAs. The other network contained 33 downregulated lncRNAs, 73 downregulated mRNAs, and 5 upregulated miRNAs. Functional analysis revealed that 38 GO terms and 8 pathways related with osteogenesis were enriched. Twenty-four osteogenesis-related gene-centred lncRNA-associated ceRNA networks were successfully constructed. Among these pathways, we highlighted MAPK and TGF-beta pathways that are closely related to osteogenesis. Subsequently, subnetworks potentially linking the GO:0001649 (osteoblast differentiation), MAPK and TGF-beta pathways were constructed. The qRT-PCR validation results were consistent with the microarray analysis. Conclusion We construct a comprehensively identified lncRNA-associated ceRNA network might be involved in the osteogenesis of PDLSCs, which could provide insights into the regulatory mechanisms and treatment targets of periodontal regeneration.

CircRNA FAT1 Regulates Osteoblastic Differentiation of Periodontal Ligament Stem Cells via miR-4781-3p/SMAD5 Pathway

The ability of human periodontal ligament stem cells (PDLSCs) to differentiate into osteoblasts is significant in periodontal regeneration tissue engineering. In this study, we explored the role and mechanism of circRNA FAT1 (circFAT1) in the osteogenic differentiation of human PDLSCs. The proliferation capacity of PDLSCs was evaluated by EdU and CCK-8 assay. The abilities of circFAT1 and miR-4781-3p in regulating PDLSC differentiation were analyzed by western blot, reverse transcription-polymerase chain reaction (RT-PCR), alkaline phosphatase (ALP), and Alizarin red staining (ARS). A nucleocytoplasmic separation experiment was utilized for circFAT1 localization. A dual-luciferase reporter assay confirmed the binding relationship between miR-4781-3p and circFAT1. It was showed that circFAT1 does not affect the proliferation of PDLSCs. The osteogenic differentiation of PDLSCs was benefited from circFAT1, which serves as a miRNA sponge for miR-4781-3p targeting SMAD5. Both knockdown of circFAT1 and overexpression of miR-4781-3p suppressed the osteogenic differentiation of PDLSCs. Thus, circFAT1 might be considered as a potential target of PDLSCs mediated periodontal bone regeneration.

Effect of Hydroxyapatite Microspheres, Amoxicillin–Hydroxyapatite and Collagen–Hydroxyapatite Composites on Human Dental Pulp-Derived Mesenchymal Stem Cells

In this study, the preparation and characterization of three hydroxyapatite-based bioactive scaffolds, including hydroxyapatite microspheres (HAps), amoxicillin–hydroxyapatite composite (Amx–HAp), and collagen–hydroxyapatite composite (Col–HAp) were performed. In addition, their behavior in human dental pulp mesenchymal stem cell (hDPSC) culture was investigated. HAps were synthesized through the following methods: microwave hydrothermal, hydrothermal reactor, and precipitation, respectively. hDPSCs were obtained from samples of third molars and characterized by immunophenotypic analysis. Cells were cultured on scaffolds with osteogenic differentiation medium and maintained for 21 days. Cytotoxicity analysis and migration assay of hDPSCs were evaluated. After 21 days of induction, no differences in genes expression were observed. hDPSCs highly expressed the collagen IA and the osteonectin at the mRNA. The cytotoxicity assay using hDPSCs demonstrated that the Col–HAp group presented non-viable cells statistically lower than the control group (p = 0.03). In the migration assay, after 24 h HAps revealed the same migration behavior for hDPSCs observed compared to the positive control. Col–HAp also provided a statistically significant higher migration of hDPSCs than HAps (p = 0.02). Migration results after 48 h for HAps was intermediate from those achieved by the control groups. There was no statistical difference between the positive control and Col–HAp. Specifically, this study demonstrated that hydroxyapatite-based bioactive scaffolds, especially Col-Hap, enhanced the dynamic parameters of cell viability and cell migration capacities for hDPSCs, resulting in suitable adhesion, proliferation, and differentiation of this osteogenic lineage. These data presented are of high clinical importance and hold promise for application in therapeutic areas, because Col–HAp can be used in ridge preservation, minor bone augmentation, and periodontal regeneration. The development of novel hydroxyapatite-based bioactive scaffolds with clinical safety for bone formation from hDPSCs is an important yet challenging task both in biomaterials and cell biology.