3 years into the project duration, SINPAIN has selected small interfering RNAs that silence the expression of IL1B and NGF (signals for inflammation and pain), defined prototypes of efficient vectors to deliver these siRNAs, and confirmed their safety and efficacy in cells. It has also produced modified hydrogels of hyaluronic acid that possess self-healing properties and that can be injected intraarticularly. Moreover, smart systems to slowly deliver the anti-inflammatory drug diclofenac in the joint have also been generated. The different prototypes have been combined in a single assembled product that constitutes the 1st Generation of SINPAIN therapeutics. All these developments are supported by an exhaustive analysis of the regulatory requirements and Quality-by-Design approaches to maximise their successful transition into clinics.
Simultaneously, significant efforts and coordination by the multidisciplinary SINPAIN team, is allowing a deeper understanding of the events leading to OA appearance. Specifically, they are depicting the contribution of the different cell types to the molecular changes that take place during OA pathogenesis by analysing human samples obtained during arthroplasty in knee with late OA. In parallel, co-culturing of relevant cell lines have been established in 3D scaffold to establish new model for OA conditions that will be tested on unique bioreactor to test the pipelines products developed in the project.
Complementary, artificial intelligence is being used to create a new tool to improve the diagnosis of OA. This is based on imaging techniques (magnetic resonance, computerised tomography and X-rays), from which relevant informative features have been successfully extracted allowing the discrimination between healthy and degenerated knees. In a further step, these will be used to distinguish different stages of the disease and allowing a more suitable medical management of each patient.
Finally, with the approval of the ethical committee, the first in vivo testing of the first generation of SINPAIN product has been currently tested on an animal OA model. The results are currently under treated to understand the effect of this new viscosupplement in early stage OA.
