E!12432 A new medical device gel that reduces chronic inflammation and restores oral soft tissue health

Periodontal diseases lead to reduction of bone and supporting tissue in the mouth, loss of tooth attachment and teeth. The focus of many of today's treatment strategies is to fight the infections with antibiotics, and without a clear strategy to stimulate the biological recovery of the lost tissue. In this project, a product has been produced consisting of a combination of a patented bioactive peptide and a gel, which upon application leads to healing and growth of the oral support tissue. This includes both fighting infection and biological stimulation to rebuild the lost tissue. Different inflammation models with gingival fibroblasts in 2D and 3D cell cultures, respectively, were developed, and the optimal concentration of the peptide was determined after characterizing the effect on viability, proliferation and differentiation. To ensure that higher concentrations did not have an adverse effect on nearby tissues or cells, concentrations up to 20x of optimal dose were tested on primary mesenchymal stem cells, osteoblasts and cancer cell lines in the same systems. Different gel combinations were tested for mechanical-physical-chemical properties such as dose and time secretion of the peptide, swelling and expansion degree, and degradation rate of the gel. A clinical protocol was developed and validated by the members of the consortium.

A new treatment strategy for periodontal diseases has been developed, which is expected to reduce treatment costs and patient discomfort and improve quality of life for a large number of EU patients. An in vitro inflammation model mimicking the chronic periodontal inflammation has been established. A manuscript is currently under preparation related to this part enabling other researchers to use the same strategy. Artificial tissue in the form of 3D models of single and co-cultures of oral cells have been established using both layer-on-layer techniques and a rotation technology where the cells recover their in vivo physiological attributes and can be maintained as large 3D tissue mimetic structures. Significant expertise has been gained in the formulation work and on sterilization techniques of advanced hydrogels.

Periodontal diseases are a major health issue affecting 47% of the population. The etiology is due to an infection leading to the destruction of hard (bone) and soft (gum) tissues. The main treatment is to treat only the infection by antibiotics. A contrario, the complementarity skills and expertise developed by project partneres will be able to design and develop a new medical device able to boost the physiological pathway responsible to regenerate the periodontium and thus treating periodontal disease. The project is multi disciplinary undertaking aiming at developing devise consisting of a peptide drug, advanced hydrogel technology and an innovative approach to test devices in synthetic tissues avoiding animal experiments and reducing systematic variations in the test, and thus reducing the overall RND costs for such a product.