Osteoarthritis is a multifactorial, degenerative joint disease characterised by progressive cartilage degradation and dysregulated inflammation. Due to the complexity of this pathology and the low vascularisation of cartilage, current treatments are mostly limited to anti-inflammatory drugs. The present project (NanoArtic) addresses the development of multicomponent biomaterials for the regenerative treatment of articular cartilage damaged by osteoarthritis. These biomaterials will be designed to respond sequentially and adaptively to the different situations that arise in the processes of tissue degeneration. To this end, our approach is based on strategies that include the chemical composition, the organisation of matter at the nanoscale, their functionalisation and the incorporation of therapeutic agents.

The project involves the synthesis and characterisation of nanoparticles and their inclusion in hydrogels for the in situ treatment of osteoarthritic lesions. Mesoporous silica and lipid nanoparticles, intended for the delivery of therapeutic agents, will be functionalised to improve retention in cartilage tissue. Efficient delivery of non-coding RNAs into chondrocytes will be evaluated with the aim of improving the state of osteoarticular pathology. These nanomaterials will be embedded in fibrin and/or hyaluronic acid-based hydrogels used for incorporation as injectables into in situ defects. Such hydrogels are categorised as adhesive and, therefore, will ensure local distribution and improved transfer efficiency of the therapeutic agents in the tissue of interest. In addition, fibrin and hyaluronic acid have immunomodulatory effects and enhance tissue regeneration. In contexts of more advanced degeneration, the use of these hydrogels as a method of delivering cells with regenerative capacity will be studied.

In order to assess the regenerative and anti-inflammatory capacity of the developed systems, in vitro studies will be performed on human mesenchymal cells, chondrocytes and immune system cells such as macrophages. Co-culture models will be used to assess cellular interactions, providing a closer approximation to the physiological context. Furthermore, the recruitment and use of mesenchymal cells for cartilage regeneration will be investigated by studying chondrogenesis induced by non-coding RNAs delivered through these systems. The most promising biomaterials for clinical application will be evaluated ex vivo. Finally, an in vivo experiment will be designed to analyse their regenerative potential in an animal model of osteoarthritis at the appropriate stage.