A longstanding challenge in accurate mechanical characterization of engineered and biological tissues is maintenance of both stable sample hydration and high instrument signal resolution. Here, we describe the modification of an instrumented indenter to accommodate nanomechanical characterization of biological and synthetic tissues in liquid media, and demonstrate accurate acquisition of force-displacement data that can be used to extract viscoelastoplastic properties of hydrated gels and tissues. We demonstrate the validity of this approach via elastoplastic analysis of relatively stiff, water-insensitive materials of elastic moduli E>1000 kPa (borosilicate glass and polypropylene), and then consider the viscoelastic response and representative mechanical properties of compliant, synthetic polymer hydrogels (polyacrylamide-based hydrogels of varying mol%-bis crosslinker) and biological tissues (porcine skin and liver) of E<500 kPa.
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