Project title: Bioactivated hierarchical hydrogels as zonal implants for articular cartilage regeneration
Degeneration of cartilage is a major cause of chronic pain, lost mobility and reduced quality of life for millions of Europeans and over 151 million osteoarthritis (OA) sufferers worldwide. Yet, despite intensive research, no clinical therapy is available that leads to healing of cartilage defects. Treatment to achieve hyaline cartilage regeneration and not only formation of fibrous repair tissue that only delays prosthesis remains a great challenge.
Current cartilage implants cannot establish the hierarchical tissue organisation that appears critical for normal cartilage function. We hypothesise that a biomimetic zonal organisation of the implants themselves is critical to induce native tissue hierarchy and thus achieve regeneration of functional hyaline cartilage.
HydroZONES represents an interdisciplinary consortium that adopts a strategy to regenerate articular cartilage based on biofunctional hydrogel-based implants that mimic the tissues zonal structure and function.
Degradable and clinically used thermoplastic polymers will be applied for mechanical reinforcement of the hydrogels. HydroZONES will follow and compare cell-free and cell-loaded hydrogels, comparing chondrocytes and bone marrow derived mesenchymal stem cells for their efficacy. Three-dimensional printing techniques will be employed for the automated assembly of the implants to guarantee reproducibility.
Scaffolds that pass our stringent and well-documented in vitro and in vivo screening will undergo long-term pre-clinical testing in minipigs and horses, which will set a new international standard for pre-clinical testing of cartilage implants.
Defined endpoint of HydroZONES is the positive long-term pre-clinical evaluation of at least one construct, according to pre-clinical regulatory requirements and in GMP standars.
Advanced bioreactors will be employed for in vitro testing of the constructs and results will be used as input for realistic in silico modelling.
Second major aim of HydroZONES is the development of a predictive 3D in vitro assay for chondral implants, validated against our in vivo results, together with the hardware to perform the assay.