Rizky Aditya Irwandi ^1,2 Crystal Marruganti ^1,3 George Collins ^4,5 Jhonatan de Souza Carvalho ^4,6 Derek W Gilroy ⁴ Francesco D'Aiuto ^1*

• ¹ Periodontology Unit, Eastman Dental Institute, Faculty of Medical Sciences, University College London, London, England, United Kingdom
• ² Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia
• ³ Unit of Periodontology, Endodontology and Restorative Dentistry, Department of Medical Biotechnologies, University of Siena, Siena, Italy
• ⁴ Department of Ageing, Rheumatology and Regenerative Medicine, Division of Medicine, University College London, London, United Kingdom
• ⁵ Department of Cardiology, St Bartholomew’s Hospital, Barts Health NHS Trust, London, United Kingdom
• ⁶ Department of Diagnosis and Surgery, School of Dentistry, São Paulo State University (UNESP), Araraquara, Brazil

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.