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Development of natural injectable biodegradable systems based on chitin and its derivatives

Final Activity Report Summary - RENEWINJ (Development of natural injectable biodegradable systems based on chitin and its derivatives)

The objective of the project was the development of injectable biodegradable systems (IBS) for regenerative medicine using an 'ecological' approach. IBS are defined as systems in liquid or dissolved form which can be prepared, mixed and handled just before implantation and that, once implanted, harden, solidify or gelify in situ, thus acquiring their final dimensions and properties in a few minutes. Most such systems under study today make use of synthetic polymers and aggressive preparation routes.

In this project, we proposed the use of a renewable and largely available material, chitin, as the main constituent of IBS. Moreover, the raw product could even originate from residues of other industries, particularly from the food industry which discards large amounts of chitin every year. To transform such raw material into an adequate IBS, we made use of enzymatic and water-based chemical processes, aiming at keeping the 'green' approach throughout the entire synthetic route. A commercially available chitin derivative, called chitosan, which was a large molecule, was firstly depolymerised to smaller oligomers which were easier to modify. Small amounts of acrylic chemical groups were then anchored to the oligomers backbone. Such acrylic groups reacted in physiological conditions and transformed the soluble oligomer in an insoluble gel. Such transformation occurred in a short time, lower than 15 minutes, and allowed for the material to be used as IBS. It degraded steadily over time, losing mass without losing its cohesiveness or initial shape. Cytotoxicity tests were performed with a fibroblast cell line and demonstrated that the material was non-toxic and adequate for use in either in vivo or clinical trials.

In summary, we succeeded in developing a 'green' strategy to prepare IBS. In general, research on IBS today is concerned only with the achievement of adequate mechanical and biological properties, without much concern about the production methodology. We demonstrated that it was possible to develop bio-based systems performing as good as synthetic ones, or even better than these, making use of renewable raw materials and non-aggressive synthesis methods. The employed methodology was very simple and could be easily translated to the industrial sector since it did not make use of toxic or aggressive solvents and therefore raised less ecological concerns regarding a possible industrialisation route. It was also an interesting technology for less-favoured countries, since both raw materials and processing routes were cheap and could help these countries to develop their own technology, decreasing their dependence on imported know-how.