Development of tuneable microgels for controlled protein delivery in tissue regeneration

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Controlled delivery of proteins, such as growth factors, is a highly promising strategy to treat pathological conditions, including bone defects and skin lesions. A major roadblock to effective protein therapeutics is the lack of biocompatible, bioactive, and injectable carriers that deliver proteins locally with high bioactivity and suitable release rates in the site of injury. Hydrogels, highly hydrated cross-linked polymer networks, have been studied as promising protein carriers that can mimic the properties of the extracellular matrix in native tissues. The encapsulation of bioactive molecules within the hydrogels would allow for the targeted and sustained delivery to the site of defect or injury, providing enough time for the tissue to heal and stimulating the tissue growth and cell differentiation. Injectable microgels with highly controlled biomechanical properties and protein release mechanisms can be developed, allowing a minimally invasive administration in the site of injury. Microgels can be produced by using microfluidics approaches, that allow the high-throughput production of spherical and monodisperse microparticles, where the targeted size can be controlled with high precision. The proposed research project will focus on the development of new microgels platforms for the efficient and controlled delivery of growth factors and mesenchymal stem cells (MSCs) to promote tissue repair. We will develop bioactive microgels with tuneable physicochemical properties, in terms of degradability and viscoelastic properties, using different natural- and synthetic- based hydrogel formulations with immunomodulatory properties and potential to promote cell proliferation, migration and differentiation, with the aim of reducing the GF doses, which will result in a safer approach. The physicochemical and mechanical properties of the microgels will be characterised and their bioactivity evaluated in vitro. Finally, the most successful microgel formulation will be tested in vivo using the relevant animal model according to the application (e.g., subcutaneous model for cartilage and diabetic mouse model for wound healing).