Towards Fibre-Integrated Hydrogels: A New Approach for 3D Hydrogel Printing & A Study of Single Cell-Microfibre Interactions

Recent advances in biofabrication have unveiled opportunities to build up biomimetic scaffolds and architectures for applications ranging from tissue engineering to bioinspired soft robotics. The structural and functional analogues of ECMs could be seen to structurally exist with two functional phases, the fibril architecture and the hydrated interstitial gel; and extensive efforts have been devoted in recapitulating these two phases by fibres and hydrogels respectively. With the above overarching motivation, this PhD project focuses on the fabrication of a synthetic medical hydrogel, as well as the investigation of cell dynamics on ECM-mimic fibrils. Firstly, a new hydrogel printing strategy, Hydrogel Embedding with Reversible Multiphase Encapsulating System (HERMES), was developed to 3D print chemically-inert and mechanically-robust polyacrylamide (PAAM) based hydrogels. In particular, pre-crosslinked alginate slurries were developed as the framework ink to bind with PAAM precursors and achieve extrusion printing; and novel oil-phase fugitive hydrophobic supporting inks were developed in order to achieve PAAM embedded-printing. HERMES strategy was employed to create volumetric hydrogel structures with geometric complexity beyond existing limitations in casting, and is applicable in printing various other hydrophilic polymers with low viscosity and slow-gelling properties. Secondly, to mimic the morphological characteristics of fibrillar matrices, low-voltage continuous electrospinning techniques was adapted to construct straight, wavy, looped and grid fibre patterns made of polystyrene. With microfibres deposited onto non-passivated surfaces, cells were able to dynamically adapt their shapes in response to the directly-adhered fibre, as well as to the neighbouring patterns; and such adaptation reflect their ability to shuttle and alter between fibre tracks. Key morphological features such as the variation of cells’ minor axis were identified for understanding cell migration in fibril matrices, as well as designing future ECM-mimic fibril models for cell migration studies. Taken together, the two parts of work have shown the feasibility of building cell-guiding hybrid architectures made of fibre-integrated hydrogels. This was the ultimate goal but due to Covid-19 pandemic restrictions, the two strategies were demonstrated separately without integration. It is envisaged that this PhD work might lay down the foundation to apply additive manufacturing approaches into future applications such as artificial muscles, biosensors and bioreactors.China Scholarship Counci