Development and optimisation of novel bioprinting process for scalable production of tissue models using FRESH technique

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Context of Research More than 5 million people in the UK are affected by Osteoarthritis (OA) every year, placing a multi-billion-pound burden on the local economy and the NHS. Despite more than 50 years of research, no effective drug is commercially available for OA. In vitro models are deemed an ethical alternative of the animal models - the most common model currently - in drug development but only simple model, typically with single tissue component, have been proposed due to their inherent scaffold related limitations, i.e. poor cell viability and instable cell phenotype. There is therefore an urgent unmet need for new technological platforms that enable reproducible and integrative human relevant OA in vitro models.Aims and Objectives Our aim is to develop biofabrication platform based on Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technology, suitable for high throughput biomanufacturing to produce standardisable and translational human relevant OA joint models.Specific objectives include:1. Characterisation and optimisation of bioinks developed by ManchesterBIOGEL used for FRESH technique 2. Tailor platform for human chondrocytes and human osteoblasts engineering for mono- and co-cultures systems 3. Characterise tissue models developed in 2 for their quality and phenotype. Establish applicability of developed models to produce standardisable and translational human relevant OA joint models. Potential application and BenefitsThe clinical presentation of OA is extremely heterogeneous, with multiple subsets of patients. Further, the pathogenesis of early OA remains poorly understood, hampering the development of effective tools for early diagnosis and disease-modifying therapeutics. Given the limited availability of human tissue, numerous animal models have been utilised over the past 50 years to study disease onset and progression, as well as to test novel therapeutic interventions. Whilst in vivo models offer a reflection of the naturally-occurring whole-joint disease, the versatility of an in vitro system, and the desire to incorporate and exploit the potential of the 3R philosophy of refining, reducing and replacing the use of animals makes in vitro modelling of the disease highly desirable. Research Methodology The project partner Manchester Biogel (MBG) commercialises a family of synthetic hydrogel products for complex biological systems. This project explores use of these hydrogels to develop scalable, standardise chondrocytes and human osteoblasts engineering for mono- and co-cultures systems for AO models development. A novel 3D fabrication technology, FRESH printing, will be explored in this project. This allows generation of complex and large tissue constructs. The student will characterise bioinks and optimised FRESH printing process using combination of computational and experimental approach. Once process is standardised, both on mono and co-culture cell printed models of osteoblast and chondrocytes will be developed. Cellular models will be tested for their survival and long-term differentiation, to establish tissue specific phenotypic development. Alignment to EPSRC strategies and research areas This project will critically contribute to two of the EPSRC healthcare technology challenges: "Developing Future Therapies" and "Optimising Treatment". It will provide fundamental tool (i.e. in vitro model) to identify future pharmacological therapy, in ethical and cost-effective manner, which will certainly lead to more optimal treatment. In the technological aspect, the project involves novel methods in "advanced materials" and "future manufacturing technologies" among the cross-cutting capabilities by providing a novel bioprinting platform.