Concept and Objectives

Whilst advances have been made in the development of hydrogels for enhanced cell survival and chondrogenesis, little attention has been paid to recapitulating the zonal structure and function of native cartilage. We hypothesise that the development of zonal properties is critical for the long-term stability and functionality of tissue-engineered cartilage and eventual cartilage regeneration.

HydroZONES will develop implants with complete anatomical reproduction of articular cartilage based on biocompatible and biofunctional hydrogels that mimic cartilage ECM (cellular level) and the natural tissue organisation and zonal structure of natural cartilage (tissue-level). The consortium proposes a hydrogel based concept featuring biomaterial-directed differentiation and bioprinting technology to restore the organisational features of the tissue. HydroZONES will develop biomimetic zonal hydrogel based constructs that will ultimately facilitate cartilage regeneration instead of commonly achieved temporary repair and thus yield a clearly improved therapeutic outcome for cartilage defects.

The consortium comprises three leading internationally recognised European laboratories in biomaterials development and hydrogel technology that will provide established but innovative hydrogel technology comprising usability in printing devices, specific functionalisation with peptides, GAGs and growth factors and finally the option to load the hydrogels with cells during printing due to cytocompatible cross-linking reactions.

Scaffolding will be addressed in HydroZONES by the application and development of 3D bioprinting technologies. Ultimately, a fully automatised system will be developed to allow the printing of cell-laden 3D hydrogels in a closed environment under sterile conditions.

HydroZONES will use human chondrocytes from OA patients and human BMSCs for initial in vitro assessment of the scaffolds. Detailed studies will be performed with these cells as well but also with the respective porcine (minipig) and equine (horse) cells for correlation with the in vivo experiments. For a defined set of experiments, also human chondrocytes from healthy patients will be employed.

HydroZONES will install a thorough testing and selection procedure through in vitro testing (conform to ISO 10993-5), biocompatibility and biofunctionality screening in nude mice and evaluation in long-term pre-clinical minipig and horse models, the best current large animal model for cartilage. Establishment of a consortium wide quality and regulatory affairs management system according to EN ISO 13485:2007 (QM/RAM) will allow to set a new internationally acceptable standard for pre-clinical testing of (osteo-) chondral implants.

HydroZONES follows 2 major objectives:

  • Objective 1: To develop a hierarchically structured hydrogel based mechanically stable scaffold that recapitulates the zonal distribution of the native articular cartilage.
  • Objective 2: To develop and validate a predicitve in vitro test system for future evaluation of products for cartilage regeneration in order to reduce the amount of necessary animal experiments in the future.