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Abstract
Osteochondral tissue comprises of complex chemical, cellular and physical gradients which pose an immense challenge for repair via traditional tissue engineering approaches. Granular hydrogels have emerged as an exciting new opportunity for control of micro- and macro- scale properties for fabrication of complex tissue environments. This thesis explores the utility of gelMA-microgel based granular scaffolds for tissue engineering, with a focus on the osteochondral interface. First, scaffolds were optimised for MSC chondrogenesis by manipulating interstitial filler volume. Higher volumes were found to promote cell sphericity, proliferation, and aggregation, which led to enhanced chondrogenic matrix deposition. Second, incorporation of bioactive Laponite® -RD and -XLG nanosilicates is explored for MSC osteogenesis. Nanosilicate inclusion significantly enhanced MSC osteogenesis but was not found to be osteo-inductive. Third, embedded extrusion printing was utilised for deposition of a bone-mimetic ink in optimised MSC-laden microgel suspensions. Photo-crosslinkable gelMA microgels allowed tuning of ink properties, thus improving robustness. Over 21 days, MSCs exhibited gradient-like chondrogenic ECM deposition away from the bone and mineralisation close to it. Lastly, vascular structures were fabricated using a casting approach for straight channels and direct writing with a sacrificial ink for complex geometries. Design of a novel PDMS-based reactor allowed channel fabrication and long-term perfusion of constructs within the same setup. Taken together, this thesis demonstrates the modularity and versatility of gelMA microgel based granular suspensions and lays the foundation for their use in the fabrication of complex tissue models replete with vasculature.
