Nanoindentation is becoming an increasingly popular tool in the biomaterials field due to its ability to measure local mechanical properties in small, irregularly-shaped or heterogeneous samples.1 Although this technique was readily adapted to the study of mineralized tissues, the application of nanoindentation to compliant, hydrated biomaterials such as soft tissues and hydrogels has led to many challenges.1 Three key concerns associated with nanoindentation of compliant, hydrated materials are inaccurate surface detection, errors due to adhesion forces, and fluid interactions with the tip.1–4