A new class of hydrogels that mimic the time-dependent squishiness of living tissues could transform how doctors repair broken bones. Current regenerative biomaterials are designed as purely elastic scaffolds—like a rubber band that snaps back instantly—but real tissues such as cartilage and bone are viscoelastic: they flow and recover slowly when pushed or pulled. This project will create hydrogels with precisely controlled viscoelastic properties, including biochemical signals that mimic the natural extracellular matrix, and will use a cutting-edge imaging technique called Brillouin microscopy to watch how these materials change as stem cells grow inside them. The team will test the best formulations in a mouse model of critical-sized bone defects—gaps too large to heal on their own. If successful, the work could lead to smarter implants that actively guide stem cells to become bone, rather than scar tissue, and that degrade at the same rate new tissue forms. The Brillouin microscope itself could become a tool for surgeons to monitor healing in real time, without needing to biopsy the site. This is fundamental science with a clear translational path: understanding how cells sense and respond to time-dependent mechanical feedback is the missing piece in designing materials that truly regenerate, rather than just replace, damaged tissue.
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Tissues are viscoelastic materials whose mechanical properties evolve with time and yet this important property has not been incorporated in the design of regenerative biomaterials. Mechanical properties of biomaterials are known to influence fundamental cellular process, including cell migration, cell growth and cell differentiation. However, most of the work to understand the mechanical properties of substrates on mesenchymal stem cell (MSC) differentiation has made use of pure elastic materials. Cells probe their environment by pulling forces and receiving mechanical feedback through membrane receptors. Since viscoelastic materials respond with a time dependent process to force, we hypothesise that viscoelasticity will play a fundamental role in the differentiation of mesenchymal stem cells and hence in the design of regenerative biomaterials. This project will develop (a) a new family of viscoelastic hydrogels with controlled properties that include biochemical functionalities (recapitulating the properties of the extracellular matrix in vivo), extreme mechanical properties (i.e. very low/high elastic and viscous properties) and mechanical gradients; and (b) Brillouin microscopy to follow the evolution of the local viscoelastic properties of these cell-laden materials as a function of time. we will use viscoelastic materials to promote bone regeneration in vivo using our critical-sized defect in the mouse radius model and, in a major attempt to move the field forward, we will further develop Brillouin microscopy to monitor the viscoelastic properties of regenerative microenvironments in vivo.
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