The translational potential of inflammation-induced skin blister human models in exploring the pathogenesis of periodontitis and its systemic health implications

Abstract

Periodontitis is a highly prevalent chronic disease. Despite decades of extensive research on the topic, a complete understanding of its immunopathogenesis, especially when linked to other inflammatory comorbidities, is lacking. Ex vivo human and in vivo animal experiments have shown the host inflammatory response's crucial role in both the disease's onset and its systemic implications. These approaches, however, remain questionable when translating these findings into real-world scenarios linked to periodontitis. A clear need for new in vivo human models is discussed, especially within the context of understanding the host response to key pathogens linked to periodontitis, such as Porphyromonas gingivalis (P. gingivalis). Therefore, a skin blister model was employed to describe the stages of the host immune response in humans after challenges by microbial and/or sterile insults. A novel human challenge model using UV-killed P. gingivalis holds promise in producing new evidence and bridging the gap of the host response to periodontitis and its links with other common chronic diseases.

Keywords: Porphyromonas gingivalis; human challenge model; periodontal disease; periodontitis; periodontitis pathogenesis; periodontitis-systemic link; self-resolving inflammation; skin blister model.

Figure 1

Intradermal injection and inflammatory exudate acquisition. A 30 gauge needle attached to a 1-ml syringe is used to administer the inflammatory stimuli into the dermis just under the epidermis. A suction chamber is then positioned and secured over the injection site at a pre-specified time-point. The negative pressure generated by an electronic vacuum machine separates the epidermis from the dermis and draws in the accumulated inflammatory exudate, including inflammatory cells and soluble mediators – in response to the introduced stimulus – at the dermis. As a result, a unilocular space between the dermis and epidermis containing inflammatory exudate is formed (an artificial blister).