Periodontitis
Periodontitis (PD) is an inflammatory disease affecting the tissues that support the teeth. The condition begins when bacteria grow on teeth surface forming microbial plaque. An over-aggressive immune response against these, leads to chronic inflammation of the periodontal tissues and the destruction of the periodontal ligaments. If left untreated PD leads to tooth loss [1] while, current evidence associate PD with systemic health of patients (e.g. cardiovascular diseases) [2].
Periodontitis is regarded as a global problem which is acute in both young adults and ageing population. It starts early in individual’s life as gingivitis (the first stage of periodontitis) affects children between 14-17 years old. The severity of the disease increases with age and thus extensive attachment loss (>4 mm) is observed for ages between 30 and 45 while, tooth loss is more pronounced for ages >50 [3]. Based on the presence of periodontal pockets ≥4 mm, it was determined that 30% of the US population has periodontitis on an average on three to four teeth. Epidemiological research in Europe, revealed that Spain, Sweden, and Switzerland ranked as the healthiest among European countries as CAL between 4 and 5 mm has been observed in 20-27% of the subjects tested (ages between 35 to 44 years old). In Germany and United Kingdom these numbers are much higher (72 and 50% respectively). Over 50 per cent of the European population is estimated to be suffering from some form of periodontitis, and more than 10 per cent have a severe form of the disease, with prevalence increasing to 70 to 85 per cent among the population aged 60 to 65 [4].
Unfortunately the effects of periodontitis are not restricted only to oral health. The relationship between poor oral health and systematic diseases has become a significant issue last decades and the overall health strategies have been adjusted to this fact. A large number of epidemiological studies are linking periodontitis with cardiovascular diseases, poor glycaemic control in diabetics, low birth weight preterm babies and a variety of other conditions [3], [5]. Although the exact mechanisms which describe this association are not yet completely clear, it has been proved that periodontal inflammation leads to an increase in circulating cytokines and inflammatory mediators that in turn damage the vascular endothelium leading to atherosclerosis and other cardiovascular disease. Nevertheless it is encouraging that the majority of the studies have shown some improvement both in diabetic control and in the condition of the arterial walls (i.e. elasticity) when periodontal treatment has been provided to the patients. The current evidence is such that prevention and treatment of periodontitis may reduce chronic systemic disease risk at both the individual and community level but for this an effective treatment strategy is needed. Although it is difficult to calculate the exact amount spent for periodontitis treatment, it is estimated that the 27 EU member states has spent almost €79 billion on oral health in 2012 which is likely to rise to €93 billion by 2020 [4].
Current treatments
The ultimate goal of periodontal therapy is to prevent further attachment loss and predictably restore the periodontal supporting structures that were lost because of the disease. Conventional nonsurgical therapy and periodontal flap procedures successfully halt the progression of the disease but eventually result in soft tissue recession that leads to poor esthetics. Moreover, conventional periodontal therapy often results in inaccessible residual pockets, which negatively affect the long-term prognosis and monitoring of the treated tooth.
These compromised outcomes could be avoided or minimized by periodontal regenerative procedures that restore the lost periodontal structures and giving an end to the inflammatory character of the disease which is harmful for the systemic health. The most popular of them include: stem cells delivery, soft tissue grafts, bone replacement grafts, root modifications and growth/ differentiation factors. Selected few are described below:
Conservative approach: This strategy includes radicular scraping and planning treatment (with the use of hand instruments, ultrasonic scalers) followed by strict hygiene. It is based on the principal that a biocompatible surface and a strict hygiene control favour the development of the innate regenerative capacity of the periodontal tissue [6]. Nevertheless research in animals and humans indicates that the tissue attachment following this procedure is not predictable.
Guided tissue regeneration: The rationale behind guided tissue regeneration is to use a physical barrier (membrane) to selectively guide cell proliferation and tissue expansion. The barrier membrane prevents gingival epithelium and connective tissue expansion and favors migration of cells from the periodontal ligament and alveolar bone into the damaged region. Toxicity due to bacterial contamination and degradation products from synthetic membranes are important drawbacks [7].
Treatment of the root surface [6] [7]: The biological concept behind surface demineralization is to improve blood clot adhesion to exposed collagen fibrils which can have positive effect on wound healing and eventually to periodontal regeneration.
Bone grafts and bone filler materials: This technique aims at the regeneration of new bone which will lead eventually to the formation of new attachment, and thus bone grafts are used. The histological findings indicate that, the ligament fibers are not functionally oriented, and even long epithelial attachments are observed at the cost of periodontal ligamentary reattachment.
Growth/ differentiation factors: This technique is based on biologically active molecules to achieve periodontal regeneration. Growth factors favor cell proliferation, cell activity, chemotaxis and cell differentiation. Critical issues are: the complexity of the periodontium, the use of very high doses of bone morphogenetic proteins and the enormous costs.
Stem cell delivery: Concentrated efforts have now moved towards stem cell-based therapeutics by transplantation of outside cells to enhance periodontal tissue regeneration and its biomechanical integration. Although recent studies reported positive effects on periodontal regeneration, this technique is limited due to the problems with stem cell isolation and their general availability [8].
By reviewing these techniques it can be concluded that although there is some regenerative potential, still there is no evidence for sufficient tissue attachment. Depending on the applied technique various toxicity issues and lack of growth related reattachment arise and hinder the periodontal regeneration. The two most important factors which affect the majority of the aforementioned techniques are:
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The oral bacterial which are attached on the tooth surface and lead to contamination.
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The formation of a junctional epithelium which is not practically attached to the tooth surface.
Objectives in PRe-FActo
Although the developed treatment strategy is still several steps away from clinical translation, eventually it is expected to delay the symptoms of periodontitis and thus the cost of oral health care is likely to be reduced for patients benefit. The consequential cost repercussion on chronic disease which are apparently linked with periodontitis (glycaemic control, CVD) are also likely to reduce for risk factor patients. Comparing with the existing treatment strategies, the main advantage of our solution is that the natural teeth of the patients will be the scaffold for PD regeneration by applying a “regenerative” layer with antibacterial properties which will promote the restoration of the damaged PD ligaments. Another benefit is the proactive character of the developed technology. The application of a thin film of the sintered biomaterial (with the antibacterial properties) on the surface of the tooth at the very beginning of the disease could prevent the accumulation of the bacterial plaque, stop the periodontitis progression and protect the systemic health of the patients. Consequently, the exact same technique could be used not only for the treatment but also for the prevention of the disease.
PRe-FActo aims to address the majority of these problems and to establish the foundations for a new regenerative strategy of the periodontal tissues. The proposed procedure is based on the use of femtosecond lasers in order to attach a new layer of a calicium phosphate on the surface of dental enamel (close to the gums). This can be described by the following steps:
a) Fill the periodontal (PD) pockets with a thin layer of hybrid bio-material (Sr and Ce ions doping for antibacterial properties).
b) Bond this material onto the surface of the root after irradiating with a femtosecond laser.
c) Coating with a chitosan layer in order to promote the growth of fibroblasts and support PD regeneration. Chitosan is not only a biocompatible material with antibacterial properties but also can be used as carrier for different proteins and growth factors.