Development of reinforced polymeric hydrogels with nanocellulose and incorporating curcumin for the therapy of osteochondral lesions

Abstract

Osteoarthritis affects about 7% of the world's population, leading to the need to establish long-term strategies for its treatment. Systems produced based on hydrogels of natural polymers can help in tissue regeneration and restitution of joint functions, however, the mechanical and rheological behavior of the formulations already available must be improved. It is also understood that the incorporation of viable cells and bioactive substances may allow, at the same time, faster cartilage regeneration and relief of clinical symptoms caused by existing lesions. Thus, the objective of this project is to develop biomaterials based on hydrogels of natural polymers, evaluating their reinforcement with nanocellulose, as well as the incorporation of viable cells and curcumin. In this study it is proposed to use the 3D printing technique to produce implantable supports, as well as to obtain formulations intended for direct intra-articular injection. The hydrogels will be produced using alginate associated with xanthan gum, collagen and/or hyaluronic acid. In the case of collagen, in particular, an additional study will be carried out, comparing commercially available products with materials obtained by the team by processing under supercritical conditions. In addition to the aforementioned polysaccharides, other biopolymers may be incorporated into the formulations, such as cashew tree gum, in order to add new properties relevant to the intended application. Such systems will be tested with different conditions of reinforcement of cellulose nanocrystals and, following, the stability against the inversion of tubes, the sterilization process, as well as their rheological and mechanical behavior will be analyzed. The hydrogels that present the best performance will be characterized in terms of microstructure and cytotoxicity. Then, the incorporation of curcumin and its release kinetics will be evaluated, as well as the association of spheroids of commercially mesenchymal stromal cells originated from dental pulp. The most promising formulations will, in the end, be submitted to the 3D bioprinting process, when applicable, or analyzed for their potential for use in injectable therapies. With this study, we hope to contribute to the development of new materials capable of acting effectively in the repair of osteoarthritis. (AU)