Water molecules play a crucial role in biointerfacial interactions, including protein adsorption and desorption. To understand the role of water in the interaction of proteins and cells at biological interfaces, it is important to compare particular states of hydration water with various physicochemical properties of hydrated biomaterials. In this review, we discuss the fundamental concepts for determining the interactions of proteins and cells with hydrated materials along with selected examples corresponding to our recent studies, including poly(2-methoxyethyl acrylate) (PMEA), PMEA derivatives, and other biomaterials. The states of water were analyzed by differential scanning calorimetry, in situ attenuated total reflection infrared spectroscopy, and surface force measurements. We found that intermediate water which is loosely bound to a biomaterial, is a useful indicator of the bioinertness of material surfaces. This finding on intermediate water provides novel insights and helps develop novel experimental models for understanding protein adsorption in a wide range of materials, such as those used in biomedical applications.
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