Biological therapy and tissue engineering approaches for the treatment of osteoarthritis

In this thesis, we aimed to find an effective therapy to treat or impede osteoarthritis (OA) and to regenerate damaged articular cartilage. To achieve this goal, inhibition of pro-inflammatory cytokines that are excessively abundant in OA joints is necessary. Furthermore, for regeneration of damaged cartilage, it is essential to increase the chondrocytes anabolism. Pharmacological therapy and tissue engineering approaches are the two most promising strategies towards cartilage regeneration.
Currently, there is no effective pharmacotherapy featuring both anti-inflammatory and anabolic effects to restore the degenerated cartilage in OA or other degenerative joint diseases. Therefore, we used an inflammatory model of human OA chondrocytes microtissues, in which after screening of 34 herbal compounds with potential anti-inflammatory and anabolic effects, VA, Epi C, PS, PCA, 4-HBA and 5-HMF were selected for further studies. We selectively identified the mechanism of action of Vanillic acid (VA) and Epimedin C (Epi C). Our results indicated that VA had significant anti-inflammatory effects through inhibition of IKK complex in NF-κB signaling and Epi C showed a significant anabolic effect by increasing the expression of collagenous and non-collagenous matrix proteins. Additionally, we developed a tunable and injectable hydrogel for drug delivery and cartilage tissue engineering by crosslinking different concentrations of HA-Tyramine (HA) with aqueous Silk-fibroin (SF) solutions. HA20/SF80 composite hydrogel showed the longest and the most sustained release profile for VA and Epi C over time, which is necessary for the long treatment duration for OA joints. Also, we showed superior ECM production in HA20/SF80 chondrocyte-laden constructs. Therefore to achieve a successful therapy for OA, the combination of all mentioned approaches in pre-clinical studies is envisioned.