Osteochondral tissue engineering and regenerative strategies

Abstract

The orthopedic field has been facing challenging difficulties when it comes to regeneration of large and/or complex defects as we come across in osteochondral (OC) cases of lesions grade 4. Autologous OC mosaicplasty has proven to be a valid therapeutic option but donor site morbidity and the lack of long-term functionality remain sources of concern. OC tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. The use of two scaffolds with optimized properties for bone and cartilage architectures combined at the time of implantation as a multilayered structure was one of the first approaches for OC large defects regeneration. Last decade strategies using a bony-like scaffold supporting a cell layer for cartilage phase were introduced. Beyond the approaches already mentioned, three other strategies were reported for OCD regeneration. One methodology was the use of two different layers with a compact interface to create an integrated bilayered scaffold before cell seeding. A second strategy was the use of a single continuous structure but with different features in each layer. The last one was the combination of hydrogel phases creating this way the possibility to have injectable systems. These promising strategies for the regeneration of complex OCDs comprise the use of different biomaterials, growth factors, and cells alone or in combination, but the ideal solution is still to be found. The interface’s mechanical properties have to be optimized. A different problem is related with the cell culture method within the 3D bilayered structures with heterogeneous properties. With the increasing demand of these stratified 3D structures new cell culture systems are required. Moreover these structures present the potential to be used as in vitro models, which is a need also because of the pressure resulting from the 3R’s principle implementation that is now occurring. Regarding this, adapted bioreactors are being developed, but more efforts are required to target this scientific demand.