3D-printed and injectable hydrogels in an ex vivo cartilage defect model

The lack of tissue grafts and other soft tissue reconstruction options has intensified the search for novel, biological methods of soft tissue regeneration. Since the technology of 3D-Biofabrication is a novel approach and has evolved significantly over the last years, we will try to develop a biomaterial in the project that offers the possibility to reduce the treatment burden of soft tissue injuries. In this project, a printable and injectable hydrogel will be produced from a combination of decellularized extracellular matrix of bovine cartilage, hyaluronic acid and silk fibroin. From these hybrids two different methodologies for fabrication of the biomaterial is deployed, in which human osteoarthritic chondrocytes are already incorporated. In one method, the hybrid hydrogels will be 3D-printed and crosslinked afterwards using a photoinitiator already mixed in the solution (also called Bioink in 3D printing). In the other method, the hybrid hydrogels will be produced as injectable hydrogels, which are also crosslinked by means of a photoinitiator. For a direct comparison of the two materials an analysis of the chondrogenic, biomechanical and biotribological properties is performed. The stability against degradation during inflammation, as can occur in osteoarthritis, is also part of the investigation. In a further step, it will be attempted and compared whether the properties and functionality of the starting hydrogels (3D-printed or injectable) can be further improved by the addition of lubricin (friction) or a glucocorticoid (anti-inflammatory). However, in order to be suitable for cartilage regeneration, the developed 3D-printed as well as the injectable hydrogel must allow a good integration into the surrounding healthy or less degraded tissue (keyword osteoarthrosis). For this purpose, an ex vivo defect model with osteochondral grafts is used, in which a defect is generated in these bone-cartilage cylinders and the hydrogels are cultivated in 3D-printed and injected form over several weeks. A comparison of cell-populated and cell-free hydrogels with native tissue is envisaged. The composition and properties of the hydrogels should ultimately enable their future use in traumatic cartilage damage (e.g., as a result of an accident) as well as in osteoarthrosis, which develops under overloading, pathological wear and tear or as a result of cartilage damage. In this way, 3D fabrication should provide patients with potential solutions for treatment, which in the future should make it possible to produce patient-specific tissue constructions for cartilage regeneration. Thus, in addition to the reproducible, customized treatment of individual patients, a reduction in costs should also be achieved.