"Old Drugs, New Tricks" - Local controlled drug release systems for treatment of degenerative joint disease.

Osteoarthritis (OA) and chronic low back pain (CLBP) caused by intervertebral disc (IVD) degeneration are joint diseases that have become major causes for loss of quality of life worldwide. Despite the unmet need, effective treatments other than invasive, and often ineffective, surgery are lacking. Systemic administration of drugs entails suboptimal local drug exposure in the articular joint and IVD. This review provides an overview of the potency of biomaterial-based drug delivery systems as novel treatment modality, with a focus on the biological effects of drug release systems that have reached translation at the level of in vivo models and relevant ex vivo models. These studies have shown encouraging results of biomaterial-based local delivery of several types of drugs, mostly inhibitors of inflammatory cytokines or other degenerative factors. Prevention of inflammation and degeneration and pain relief was achieved, although mainly in small animal models, with interventions applied at an early disease stage. Less convincing data were obtained with the delivery of regenerative factors. Multidisciplinary efforts towards tackling the discord between in vitro and in vivo release, combined with adaptations in the regulatory landscape may be needed to enhance safe and expeditious introduction of more and more effective controlled release-based treatments with the OA and CLBP patients.