ERA-NET: Mar. Origin Biopolymers as Inno. Building Blocks from the Sea for the Development of bioresorbable Multilayered Membranes

The BLUETEETH project aimed to utilize biomaterials from marine resources, marine polysaccharides, to develop innovative, robust, and degradable membranes to promote bone regeneration and combat periodontal disease. Various forms of chitosan isolated from the shell of cold-water series were extracted. Influence of acetylated and differences in molecular weight were tested, and the degree of acetylation were found to affected their bioactivity. Membranes with varying numbers of layers were further tested for stability and effect on human cell growth. Composite freestanding multilayer membranes were found to stimulate cell growth and regeneration, but the effect depended on parameters such as degree of deacetylation, molecular weight and viscosity of the chitosan batch used. Selective stimulation of bone regeneration using specific peptides was further analyzed. Different membrane-peptide variants were generated using chemical methods, and tested with the aim to identifying optimal thickness, optimal production conditions, in vitro biological performance and preclinical functionality. The goal was to identify the parameters that will improve the reconstruction potential of the tissue in a clinical situation. In this interdisciplinary project, the partners in BLUETEETH had their specific tasks; from the isolation of marine raw materials to a product that is suitable for market entry and the result depended on a well-functioning collaboration and interaction.

BLUETEETH aimed at valorising marine by-products by converting the marine residues into high added-value products for healthcare applications, namely to treat periodontal disease. BLUETEETH aims at maximising the value of chitosan (CHT), which is the derivative of the most abundant polysaccharide in the sea, chitin. This was achieved through synergistic interaction and highly dynamic interdisciplinary collaboration between the BLUETEETH partners, which includes research institutions, SMEs and dental clinic facility. The end product is a pioneering asymmetric free-standing multilayered membrane/device with one side chemically modified to have slow-degradable behavior intended to inhibit the grow of soft tissue, and the other actively coated with stimulatory agents known to assist bone healing by stimulating the regeneration of bone in periodontal pockets. This strategy meet the urge in dentistry for new methodologies to induce direct re-growth of lost or damaged oral bone tissue.

The marine environment is a source with countless diversity of molecules and materials with specific biological and chemical features. In particular, several biopolymers obtained from marine organisms are currently being investigated for different biomedical applications, namely tissue engineering and drug delivery. The world capture of marine organisms including aquaculture (mainly fish, molluscs and crustaceans) amounts to 132 million tons [Mar Drugs (2013) 11, 747]. Among them, more than 35% of the total weight is handled as by-product and waste that include animal fractions (skeletons, heads, viscera) generated in seafood production or species, sizes or qualities without commercial value (discards, by-catch). Such biomass possesses a tremendous potential as a source of great amounts of macromolecules with a spectrum of chemical variety vaster than the one that can be achieved by synthesis and standard chemical approaches. The inherent renewable character of such marine sources will lead to materials with a lower carbon footprint at the end of product cycle and to a valuable alternative to polymers derived from petroleum sources, which in an era of increasing oil prices, global warming and other environmental problems (e.g. waste), is a quite relevant issue. Additionally, the investment in the blue biotechnology sector is particularly strategic for Portugal and Scandinavian countries with long shore lines and tradition in sea exploration, such as Iceland and Norway. In this sense, BLUETEETH aims at valorising marine by-products by including a SME (PRIMEX), from the marine biotechnology sector, that will convert the marine residues in high added-value products for healthcare applications, namely to treat periodontal disease. Such applicability will be enhanced by counting on a partner (UiO) that it?s strategically located at and hosts dental clinic facilities, thus supporting practically oriented research and identifying opportunities for commercialisation and mar