Third party funded individual grant
Start date : 01.01.2018
End date : 31.12.2019
There is an immense clinical need for readily available, off-the-shelf synthetic scaffolds for tendon and ligament repair. However, engineering the extraordinary tensile mechanical strength and stiffness of native load-bearing tendons and ligaments, whilst possessing high equilibrium water content (~70%), and the ability to support cell adhesion and proliferation exhibited in tendon extracellular matrix (ECM) remains an immense challenge. The Australian partner has developed a novel synthetic tendon/ligament scaffold demonstrating the above features, with which we will perform in vivo implantation of these scaffolds into surgically-induced tendon defects, in order to investigate the in vivo bridging capability of the scaffold with the native tendon tissue. Synthesis of the scaffolds would be carried out with techniques developed at the University of Sydney, whereas the scaffold-tissue interaction would be examined under label-free multiphoton imaging and quantitative morphometry analysis at Friedrich-Alexander-University Erlangen-Nuremberg.
During the project, the Australian partner (Hala Zreiqat, HZ) will focus on the material aspect and perform in vivo implantation experiments, while OF performs in vitro cell seeding and multiphoton imaging to study cell-scaffold interactions on manufactured materials to provide process engineering feedback to HZ:
1. The Australian lab will prepare 3D printed bioceramics scaffolds with different patterns to be both (i) sent to the German team for in vitro investigation of cell seeding efficiency, cell penetration kinetics with mesenchymal stem cells and progenitor cells and extracellular matrix production using advanced multiphoton second harmonic generation (SHG) microscopy to determine optimization conditions, and (ii) perform in vivo implantation of scaffold constructs in tendon/bone defects in sheep models to determine vascularization and engineered tissue integration.
2. The Sydney group will send explants from (1, ii) to the German team for detailed ultrastructural and wound healing assessment on a cellular level.
3. Both teams will optimize culture conditions and design bioreactors to improve ECM production and stem cell differentiation prior to implantation.
Both teams will perform biomechanics stability and durability tests in cell-seeded scaffolds over time using crush and strain-stress relationship tests