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Historically, broad-spectrum antibiotics have represented a major component of the therapeutic armamentarium used to treat common oral diseases associated with a bacterial etiology. The fact that these diseases are due to the accumulation of multispecies biofilms composed of ever-increasing numbers of resistant organisms has dramatically affected the efficacy of many of these drugs. Furthermore, it is now appreciated that repeated use of broad-spectrum antibiotics also affects the composition of the host commensal microbiota, which can have both local and systemic implications. In recognition of the limitations of classical antibiotics, alternative chemical, physical, and mechanical strategies are either in use or development. These include novel narrow-spectrum antimicrobials such as antitoxins, bacteriophages, and antibody-conjugated drugs that can target specific microbes while minimizing the emergence of resistant organisms and preserving eubiotic microbes. Other approaches, such as new broad-spectrum non-antibiotic strategies and probiotics, are aimed at disrupting or altering the composition of oral biofilms and their extracellular matrices to facilitate the elimination of overt pathogens by the host response and/or adjunctive antimicrobials. This critical review describes the use and limitations of broad- and narrow-spectrum strategies currently being used to treat common bacterially induced oral diseases as well as alternative methods in development. 

The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs’ response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures. 

The precise spatiotemporal control and manipulation of fluid dynamics on a small scale granted by lab-on-a-chip devices provide a new biomedical research realm as a substitute for in vivo studies of host–pathogen interactions. While there has been a rise in the use of various medical devices/implants for human use, the applicability of microfluidic models that integrate such functional biomaterials is currently limited. Here, we introduced a novel dental implant-on-a-chip model to better understand host–material–pathogen interactions in the context of peri-implant diseases. The implant-on-a-chip integrates gingival cells with relevant biomaterials – keratinocytes with dental resin and fibroblasts with titanium while maintaining a spatially separated co-culture. To enable this co-culture, the implant-on-a-chip's core structure necessitates closely spaced, tall microtrenches. Thus, an SU-8 master mold with a high aspect-ratio pillar array was created by employing a unique backside UV exposure with a selective optical filter. With this model, we successfully replicated the morphology of keratinocytes and fibroblasts in the vicinity of dental implant biomaterials. Furthermore, we demonstrated how photobiomodulation therapy might be used to protect the epithelial layer from recurrent bacterial challenges (∼3.5-fold reduction in cellular damage vs. control). Overall, our dental implant-on-a-chip approach proposes a new microfluidic model for multiplexed host–material–pathogen investigations and the evaluation of novel treatment strategies for infectious diseases. 

In this paper, we introduce an oral motion-powered Smart Tooth system that can monitor oral health. Lower pH is an indicator of bacterial accumulation in the oral cavity, which can cause tooth decay, periodontal or peri-implant diseases. Thus, in situ monitoring pH inside of the mouth is critical to prevent oral diseases. Using a piezoelectric dental crown, Smart Tooth system converts oral motions, such as chewing, to electrical power which can impinge a surface integrated LC transponder. The LC transponder also incorporates iron oxide nanoparticles-embedded pH-sensitive hydrogel that modulates the resonant frequency via shrinking or swelling. As a proof of concept, the fabricated prototype measures pH levels ranging from pH 4 to 12 and sends data wirelessly to the receiver placed up to 5 cm away (wireless transmission path loss at 3 cm was 50.79 dB). The results indicate that the Smart Tooth system can monitor oral health while replacing missing teeth.