All synthetic and natural materials to be used in biomedical applications that involve the contact with human body need to be investigated for their physical and chemical modification induced by the human physiological fluids contact and sorption. The development and testing in human physiological equivalent fluids of new hybrid biomaterials are presented. The role of water and its equilibrium modification in the human physiology is discussed and the swelling and sorption behavior in the physiological environment of a nanostructured and osteoconductive biomaterials based on Poly-Hydroxyl-Ethyl-Meth Acrylate matrix (pHEMA) filled with fumed amorphous nanosilica particles is presented. This material differently swells in presence of aqueous physiological solution fluid. Biological hybrid scaffolds for bone regeneration and growth made using synthetic materials able to correctly interact with the physiological fluids while inducing the growth of biological tissues may favor the birth in the medical field of a new class of hybrid materials. Our multidisciplinary approach explores in the this paper, novel ideas in modeling, design and fabrication of new nanostructured scaffolding biomaterials with enhanced functionality and improved interaction with OB cells.