Periodontitis is a chronic complex inflammatory disease associated with a destructive host immune response to microbial dysbiosis, leading to irreversible loss of tooth-supporting tissues. Regeneration of functional periodontal soft (periodontal ligament and gingiva) and hard tissue components (cementum and alveolar bone) to replace lost tissues is the ultimate goal of periodontal treatment, but clinically predictable treatments are lacking. Similarly, the identification of biomarkers that can be used to accurately diagnose periodontitis activity is lacking. A relatively novel category of molecules found in oral tissue, circular RNAs (circRNAs) are single-stranded endogenous, long, non-coding RNA molecules, with covalently circular-closed structures without a 5’ cap and a 3’ tail via non-classic backsplicing. Emerging research indicates that circRNAs are tissue and disease-specific expressed and have crucial regulatory functions in various diseases. CircRNAs can function as microRNA or RNA binding sites or can regulate mRNA. In this review, we explore the biogenesis and function of circRNAs in the context of the emerging role of circRNAs in periodontitis pathogenesis and the differentiation of periodontal cells. CircMAP3K11, circCDK8, circCDR1as, circ_0062491, and circ_0095812 are associated with pathological periodontitis tissues. Furthermore, circRNAs are expressed in periodontal cells in a cell-specific manner. They can function as microRNA sponges and can form circRNA–miRNA–mRNA networks during osteogenic differentiation for periodontal-tissue (or dental pulp)-derived progenitor cells.

Objectives This study evaluated particle spread associated with various common periodontal aerosol-generating procedures (AGPs) in simulated and clinical settings. Materials and methods A simulation study visualized the aerosols, droplets, and splatter spread with and without high-volume suction (HVS, 325 L/min) during common dental AGPs, namely ultrasonic scaling, air flow prophylaxis, and implant drilling after fluorescein dye was added to the water irrigant as a tracer. Each procedure was repeated 10 times. A complementary clinical study measured the spread of contaminated particles within the dental operatory and quantified airborne protein dispersion following 10 min of ultrasonic supragingival scaling of 19 participants during routine periodontal treatment. Results The simulation study data showed that air flow produced the highest amount of splatters and the ultrasonic scaler generated the most aerosol and droplet particles at 1.2 m away from the source. The use of HVS effectively reduced 37.5–96% of splatter generation for all three dental AGPs, as well as 82–93% of aerosol and droplet particles at 1.2 m for the ultrasonic scaler and air polisher. In the clinical study, higher protein levels above background levels following ultrasonic supragingival scaling were detected in fewer than 20% of patients, indicating minimal particle spread. Conclusions While three common periodontal AGPs produce aerosols and droplet particles up to at least 1.2 m from the source, the use of HVS is of significant benefit. Routine ultrasonic supragingival scaling produced few detectable traces of salivary protein at various sites throughout the 10-min dental operatory. Clinical relevance The likelihood of aerosol spread to distant sites during common periodontal AGPs is greatly reduced by high-volume suction. Clinically, limited evidence of protein contaminants was found following routine ultrasonic scaling, suggesting that the the majority of the contamination consisits of the irrigant rather than organic matter from the oral cavity.

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Regenerative medicine involves the restoration of tissue or organ function via the regeneration of these structures. As promising regenerative medicine approaches, either extracellular vesicles (EVs) or bioprinting are emerging stars to regenerate various tissues and organs (i.e., bone and cardiac tissues). Emerging as highly attractive cell-free, off-the-shelf nanotherapeutic agents for tissue regeneration, EVs are bilayered lipid membrane particles that are secreted by all living cells and play a critical role as cell-to-cell communicators through an exchange of EV cargos of protein, genetic materials, and other biological components. 3D bioprinting, combining 3D printing and biology, is a state-of-the-art additive manufacturing technology that uses computer-aided processes to enable simultaneous patterning of 3D cells and tissue constructs in bioinks. Although developing an effective system for targeted EVs delivery remains challenging, 3D bioprinting may offer a promising means to improve EVs delivery efficiency with controlled loading and release. The potential application of 3D bioprinted EVs to regenerate tissues has attracted attention over the past few years. As such, it is timely to explore the potential and associated challenges of utilizing 3D bioprinted EVs as a novel ‘cell-free’ alternative regenerative medicine approach. In this review, we describe the biogenesis and composition of EVs, and the challenge of isolating and characterizing small EVs - sEVs (< 200 nm). Common 3D bioprinting techniques are outlined and the issue of bioink printability is explored. After applying the following search strategy in PubMed: ‘bioprinted exosomes’ or ‘3D bioprinted extracellular vesicles’, eight studies utilizing bioprinted EVs were found that have been included in this scoping review. Current studies utilizing bioprinted sEVs for various in vitro and in vivo tissue regeneration applications, including angiogenesis, osteogenesis, immunomodulation, chondrogenesis and myogenesis, are discussed. Finally, we explore the current challenges and provide an outlook on possible refinements for bioprinted sEVs applications.