As inspired by HKU’s recent research and development strategies, the Division successfully organized a research retreat on April 25, 2023, to set divisional mission, vision, and core values as shown above; identify the innovative research framework (Fig. 1) and themes as shown below (Figs. 2-7); and yet formulate actionable work plans via multidisciplinary collaborations and teamwork.
The innovative research framework of the Division
1. The aetiopathogenesis of periodontal / peri-implant diseases and translation potentials
One line of studies explores how periodontopathogens (e.g., Porphyromonas gingivalis)-induced dysbiotic plaque biofilms lead to destructive immuno-inflammatory responses. One focus is the interaction of dipeptidyl peptidase-4 (DPP4) with the antioxidative stress nuclear factor erythroid 2–related (Nrf2). Notably, DPP4 inhibitors (DPP4i) as an antidiabetic drug can reduce the accumulation of reactive oxygen species (ROS) via activating Nrf2. Herein, the altered periodontal microanatomy is analyzed to understand the potential involvement of Nrf2-regulated gene transcription and NF-κB-RANKL signaling pathway in mouse periodontitis models. This study aims to unravel the role of oxidative distress in periodontal pathogenesis and develop DPP4i-based strategies for oral healthcare. This work may pave the way for novel therapies to manage periodontitis and related bone conditions driven by oxidative distress and inflammation (Fig. 2).
Oxidative stress-influenced mesenchymal stem cells (MCSs) differentiation and macrophage-osteoclast axis modulation may underpin host-mediated periodontal destruction (Li & Leung, pending publication)
Another line of pioneering work investigates the pathogenicity of the keystone periodontopathogen- Porphyromonas gingivalis and its persisters (first reported by the divisional team), how its persisters interact with host cells and disrupt innate defense response (Figs. 3A/B), as well as the further development of novel tackling strategies and approaches like the novel Bi-metal-organic framework (Bi-MOF) nano-systems recently established by the divisional team (Fig. 3C).
Novel strategies to detect and eliminate recalcitrant Porphyromonas gingivalis (Pg). Invasion of Pg persisters (A) into gingival epithelial cells (B) (Wang, … Jin, Antimicrob Agents Chemother 2020) and the Bi-metal-organic framework nano-systems (C) (Huang, …Li & Jin, Mater Today Bio 2023).
2. Clinical screening, early diagnostic and healthcare approaches
The collaborative teamwork of the Division attempts to establish novel screening and assessment approaches to identifying periodontal/peri-implant diseases (e.g., AI-based tools and salivary biomarkers), and develop advanced imaging techniques/digital workflows for precise diagnosis, digital virtual treatment planning and timely professional healthcare (e.g., ultrasound and computerized tomography) (Fig. 4).
Novel non-invasive detection of periodontal bone destruction (Tanaka, … Leung, ... Pelekos, 2023)
3. Periodontal medicine and healthy aging
Recently, the divisional team has reported for the first time that periodontal diseases closely link to multiple systemic comorbidities (Fig. 5), and periodontal intervention has favorable effects in medically compromised patients (e.g., improved cardiac function in type 2 diabetic patients). Further studies would identify the translational potentials and undertake clinical trials on the connection of periodontitis and systemic inflammatory comorbidities/disease modules.
The oral-systemic diseases axis (Jin, 2022).
Obesity as a significant metabolic disorder increases the risk of periodontitis. Notably, exercise is a practical non-pharmacological approach to favorably regulating obese-related metabolic disorders and bone health. Currently, the mechanisms underpinning how physical exercise modulates the negative effect of obesity on periodontal homeostasis remain unclear. Remarkably, exercise closely links to multiple systemic factors and pathways that affect bone health, hormones, inflammatory cytokines, microbiomes and osteogenic signals like Wnt/β-catenin and OPG/RANKL/RANK. The divisional team has shown that exercise attenuates the bony impairment in jaws and tibias induced by a high-fat diet with altered levels of certain free fatty acids and cytokines. The further work can uncover the molecular link between exercise and bony changes from microbiological, metabolomic and multi-omics aspects (Fig. 6).
The mechanisms underpinning obesity-related systemic & alveolar bone loss (Zhao,… Leung, 2022)
The world is facing the crisis of rapid population aging, and the global burden of age-related diseases becomes a major public health problem. Severe tooth loss/edentulism due to periodontitis crucially accounts for accelerated aging and mortality, while the underlying mechanisms remain unclear. In more recent years, the topic of ageing has been discussed in relation to frailty. Frailty is a state of decreased physiologic reserve and resistance to stressors. It can lead to increased adverse outcomes, such as loss of mobility and independence. The pathological processes hypothesized to be responsible for the development of frailty include chronic inflammation and immune activation, sarcopenia (loss of muscle mass and strength), and age-related changes to the endocrine system, such as a decrease in the sex hormones, higher levels of cortisol, and vitamin D deficiency. It is well-known that frail older people are vulnerable to geriatric syndromes which include cognitive diseases such as Alzheimers disease. Additionally, “inflammageing” has been conceptualized as a shared risk factor and pathophysiological mechanism between cardiovascular diseases and frailty highlighting the complex interplay between aging, frailty, and chronic diseases. Furthermore, the association of frailty with adverse outcomes in surgical patients has gained recognition in the last few years yet mostly exists in the medical literature.
The divisional team would investigate the interplay of periodontal inflammation, frailty, chewing dysfunction, dietary intake and nutrition in accelerated aging, and seek to implement new theragnostic strategies for promoting and enhancing healthy aging, through populational-based preclinical and clinical studies.
4. Severe periodontitis: therapeutic approaches, functional rehabilitation and well-being
Globally, 5-20% of adults are susceptible to severe periodontitis and the resultant massive toothlessness, dramatically affecting patients’ quality of life and well-being. The divisional experts are committed to refining the current therapeutic procedures and implant-based functional rehabilitation approaches to provide individualized treatments for better managing severe periodontitis patients and medically compromised ones (e.g., chronic kidney disease cases) (Figs. 7A/B).
The human brain as a vital organ is in close proximity to the mouth, and dynamically senses and controls oral functions and related behaviors. Psychoneuroimmunological disorders put the patients at risk of periodontal diseases, neurodegeneration, poor general health and accelerated aging. An ongoing divisional project investigates whether and how periodontal health/professional care could account for maintaining proper neural function and overall well-being, Advanced approaches like magnetic resonance imaging (MRI) are used for assessing cognitive changes in patients with different severities of periodontitis (Fig. 7C). As such, patient-centered therapeutic outcome measures are well integrated in the pioneering research work, via assessment of self-reported functional profiles and capacities like masticatory efficiency, nutritional intake, self-esteem measurements and related quality of life. Moreover, further translational and clinical studies are undertaken to refine the emerging treatment modalities (e.g., probiotic intervention and newly developed nano-based theranostic systems), for optimal oral/periodontal healthcare (Fig. 7D).
Clinical management, innovations, and interventions for periodontitis (A/B), studies on assessing treatment outcomes like fMRI-based analysis of improved neural functions and beyond in treated periodontal patients (C) (Fok, Tarce, Deng, Tsang, Goh, Pelekos, Jin & Leung 2023), and development of novel theranostic nanosystems (D) (Li,… Jin, J Colloid Interf Sci 2022) for periodontitis management.
