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Sensing peri-implant disease

Final Report Summary - STEP (Sensing peri-implant disease)

Peri-implant disease is a true threat in today`s advancement of implant reliability and performance. The aim of the STEP project (Sensing peri-implant disease) is to develop a new and easy to use diagnosis tool for early detection of peri-implant diseases. The delayed recognition of peri-implant complications which are typically recognized only once clinical signs appear – a stage at which the disease course may be irreversible and lasting complications may prevail at the site of the implant zone. A treatment at this late stage is difficult and results often in irreversible bone degradation. Early diagnosis of peri-implant disease would avoid irreversible bone loss and permanent complications and help to apply existing therapies. The STEP project is a multidisciplinary approach that combines innovative technologies emerging from biochemistry, surface engineering, and dentistry. The diagnosis is based on biomarker recognition and aims to allow self-monitoring by the patient. This fact renders the system truly disruptive and radically opens novel opportunities for early diagnosis and treatment modalities of peri-implant disease.

A recent consensus meeting has concluded that peri-implant disease occurs in 12 – 40% of dental implants [4]. This renders peri-implant disease a true threat in today’s advancement of implant reliability and performance [5]. The proposal is addressing this challenge by deploying the human sense of taste / gustatory system for surveillance of connective tissue degradation, which marks the borderline between gingivitis/mucositis and periodontitis/peri-implantitis (Figure 1). This radically new and easy to use diagnostic tool, will identify and stratify subjects at risk for development of peri-implant disease, opening a new window of opportunity for medical risk assessment and, therefore, possible intervention at an early stage. This early on detection will allow pre-emptive, successful, non-complex and well tolerated treatment. The strategy followed within this consortium is disruptive in terms of shifting current point-of-care (PoC; i.e. the practitioner’s office) diagnosis to self-monitoring, allowing consultation of one’s dentist in diseases stages which are clinically unapparent and within which relatively moderate therapeutic intervention suffice to prevent further destruction of the implant and surrounding tissues and in contrast to more radical interventions necessary at later stages.

The disease course of peri-implant infection and its most severe form, peri-implantitis, commences from microbial challenge and biofilm formation. The microbial challenge triggers a defensive host response (release of cytokines and other signals) in response to bacterial mediators e.g. lipopolysaccharides (LPS; component of the cell wall of gram- bacteria), leading to massive infiltration of macrophages (Φ). It is these Φ which are capable of releasing various proteolytic enzymes, including MMPs. Among many other MMPs tested, MMP-8 - also known as type II collagenase – has demonstrated impressive prognostic power to predict clinical progression through enhanced pocket formation, attachment loss, bone resorption, gingival recessions, increased tooth/dental implant mobility and finally tooth/dental implant loss [6] and [7, 8]. MMP-8 is disrupting the dense tissue collagen network thereby allowing efficient Φ infiltration as a prerequisite for bacteria removal – in other words, MMP-8 activity is directly linked to the first and clinically fully reversible stage of gingival connective tissue destruction (Figure 1, second and third boxes from top [1, 9]). MMP-8 upregulation in peri-implant infection is massive as compared to other inflammatory dental disease [10] and therefore, MMP-8 is an ultra-sensitive, prognostic biomarker for sensing peri-implant disease long before more severe disease states are attained, such as peri-implantitis. The challenge is to enable the subject for self-monitoring of MMP-8 activity using the system (conceptually presented in Figure 1) and functionality is achieved as outlined in Figure 2.