Oral and dental health is an important indicator and determinant of an individual’s overall well-being. Untreated oral diseases can lead to severe systemic complications. Monitoring the oral environment and identifying biochemical and physiological patterns associated with disease states, such as periodontitis, gingivitis, caries, and oral cancers, is essential for early diagnosis and effective intervention. This review evaluates the current clinical needs in biochemical and physiological monitoring for oral healthcare and state-of-the-art biosensors capable of continuous analyte measurement. We surveyed the relevant biomarkers for common oral and dental diseases in patients compared to healthy controls. The design and performance of recent biosensing devices for these target analytes are reviewed and evaluated. For biochemical sensing, we found intraoral biosensors for high-abundance small molecules, such as ions and metabolites, have advanced significantly in recent years. However, robust sensing technologies for low-abundance analytes, including cytokines and other inflammatory biomarkers, remain limited and require further development in sensing mechanisms, bio-interfaces, and device integration. For physiological sensing, particularly the measurement of forces in tooth movement, recent developments in force sensor technologies have substantially improved measurement accuracy over traditional techniques. Despite these advancements, current platforms still face limitations in achieving long-term, real-time monitoring of mechanical conditions within the oral cavity due to challenges related to biocompatibility and device miniaturization. In conclusion, while notable progress has been made in biosensing for oral applications, continued research in device integration with clinical practices is essential to realize robust and clinically deployable biosensor systems that can advance precision oral healthcare.

Long-range intercellular communication is essential for multicellular biological systems to regulate multiscale cell–cell interactions and maintain life. Growing evidence suggests that intercellular calcium waves (ICWs) act as a class of long-range signals that influence a broad spectrum of cellular functions and behaviors. Importantly, mechanical signals, ranging from single-molecule-scale to tissue-scale in vivo, can initiate and modulate ICWs in addition to relatively well-appreciated biochemical and bioelectrical signals. Despite these recent conceptual and experimental advances, the full nature of underpinning mechanotransduction mechanisms by which cells convert mechanical signals into ICW dynamics remains poorly understood. This review provides a systematic analysis of quantitative ICW dynamics around three main stages: initiation, propagation, and regeneration/relay. We highlight the landscape of upstream molecules and organelles that sense and respond to mechanical stimuli, including mechanosensitive membrane proteins and cytoskeletal machinery. We clarify the roles of downstream molecular networks that mediate signal release, spread, and amplification, including adenosine triphosphate (ATP) release, purinergic receptor activation, and gap junction (GJ) communication. Furthermore, we discuss the broad pathophysiological implications of ICWs, covering pathophysiological processes such as cancer metastasis, tissue repair, and developmental patterning. Finally, we summarize recent advances in optical imaging and artificial intelligence (AI)/machine learning (ML) technologies that reveal the precise spatial-temporal-functional dynamics of ICWs and ATP waves. By synthesizing these insights, we offer a comprehensive framework of ICW mechanobiology and propose new directions for mechano-therapeutic strategies in disease diagnosis, cancer immunotherapies, and drug discovery.

Diabetes is a risk factor for periodontitis. Increasing evidence suggests that a central player in this link is the vacuolar H+-ATPase (V-ATPase), which provides a physical and functional core for regulation by the catabolic lysosomal AMP-activated protein kinase complex (L-AMPK) and the anabolic mammalian target of rapamycin complex 1 (mTORC1). These complexes detect levels of various cellular nutrients, including glucose at the lysosome, and promote cellular responses to restore homeostasis. The high-glucose conditions of diabetes foster anabolic mTORC1 signaling that increases inflammation and inflammatory bone resorption in response to periodontal infections. Here, we review the structure and composition of V-ATPase, L-AMPK, mTORC1, and other elements of the energy-sensing platform. Mechanisms by which V-ATPase passes signals to the complexes are examined and recent data are reviewed. Current anti-bone resorptive therapeutics, bisphosphonates and denosumab, enhance the risk of medicine-related osteonecrosis of the jaw (MRONJ) and are not used to treat periodontal bone loss. Accumulating data suggest that it may be possible to target inflammatory bone resorption through agents that stimulate L-AMPK, including metformin and glucagon-like peptide-1 agonists. This approach may reduce inflammatory bone resorption without major effects on overall bone remodeling or increased risk of MRONJ.

Bone, cartilage, and their composites in various joints are the most important components that form the skeletal structure and enable motion and movements of the body. Their disease and/or loss are most debilitating and afflict millions of Americans, reducing productivity and deteriorating quality of life. Due to limited treatments, scientists, engineers, and clinical doctors are investigating new tissue engineering solutions. In tissue engineering approaches, scaffolds are artificially designed temporary matrices that accommodate stem/progenitor cells and provide both physical and biological signals to guide cell differentiation and 3D tissue regeneration but eventually degrade and leave behind regenerated functional tissues or organs. Therefore, scaffolds often substantially benefit from mimicking certain features of the natural extracellular matrix (ECM) and designing certain engineered features to facilitate cell repopulation, mass transportation, and mechanical and biological cues for cells to regenerate tissue. This review article focuses on the design, synthesis, fabrication, and functionalization of nanofibrous materials to mimic the ECM, deliver biological signals, and integrate various engineering design features such as pore shape, size, connectivity, tissue architectures, and anatomic tissue/organ shapes to guide 3D tissue regeneration. In addition to biological and physical principles of scaffold design and fabrication, we also provide several examples of specific applications of these advanced nanofibrous scaffolds for bone, cartilage, and their associated composite tissue regeneration in osteochondral defects. We also discuss the interdisciplinary and multidisciplinary nature of these research directions, the importance of collaborations across disciplines, and the perspectives of future developments in the field.

Purpose This cross-sectional survey study investigated how two-dimensional (2D) versus three-dimensional (3D) facial representations influence perceived facial attractiveness, treatment need, and treatment modality selection across a range of sagittal and vertical facial patterns. Methods Standardized facial images of one male and one female subject were digitally modified independently in the anteroposterior (AP) and vertical dimensions using FaceGen software to generate nine variations per subject (three sagittal × three vertical), resulting in 18 facial depictions. Two anonymous surveys were constructed using REDCap: a 2D survey with static frontal and profile images and a 3D survey with rotating facial models. Each survey included the same set of modified faces presented in different visualization formats. A total of 400 evaluators including students, dentists, specialists, and laypeople recruited from a university-based population participated in the study. Participants rated facial attractiveness using a visual analog scale and assessed perceived treatment need using a 5-point ordinal scale. For profiles requiring treatment, participants selected the preferred modality (orthodontic treatment alone vs combined orthodontic–surgical treatment). Statistical comparisons between 2 and 3D assessments were performed using Wilcoxon rank-sum and Fisher exact tests. Results Three-dimensional visualization significantly influenced esthetic perception and clinical decision-making. Among male profiles, selected Class II and Class III patterns were rated more attractive in 3D, whereas others were rated less attractive compared with 2D images. Female Class II and Class III profiles consistently demonstrated higher attractiveness scores in 3D (P < 0.001). Perceived treatment need was generally lower in 3D evaluations, with increased “no need” ratings for several profiles (e.g., Class I and Class II) and a reduction in “very great need” ratings for severe Class III patterns. Three-dimensional visualization also reduced the frequency of combined orthodontic–surgical treatment recommendations, with more profiles considered suitable for orthodontic treatment alone. Conclusions Compared with static 2D images, 3D representations modify facial morphology perception and are associated with less severe treatment modality selections, suggesting that integration of 3D facial imaging into orthodontic diagnosis and treatment planning may lead to different clinical management decisions.