Instructive composites for bone regeneration

Developing new biomaterials for tissue regeneration requires careful balance between many factors, which is challenging because, on one side, such materials must provide complex information, through their physicochemical properties to actively interact with the biological surroundings and induce tissue regeneration. On the other side, regulatory issues, costs and ease of use of the final device, require low system complexity. For this reason, an emerging strategy is not attempting to recreate the complexity of tissues in vitro, but to focus on synthetic materials that have ‘intrinsic’ features that can instruct cells in vivo finally determining their fate. Therefore, newly developed biomaterials should be carefully designed to have specific local characteristics (e.g. surface stiffness, chemistry and topography) that can induce controlled cellular behaviors ultimately leading to tissue regeneration. In bone tissue regeneration by biomaterials, such instructing phenomenon is referred as ‘osteoinduction’. In this thesis we aimed to develop simple biomaterial systems, i.e. composites of two phases (i.e. polymer and calcium phosphate) that could be able to interact with the biological system. In particular, we have striven to understand the role of some ‘intrinsic’ characteristics of the composite phases (e.g. calcium phosphate content, polymer molecular weight and monomer chemistry) in determining crucial phenomena occurring at the interface between biomaterial and biological environment. Such surface processes, e.g. surface mineralization and protein adsorption, play key roles in instructing (stem) cells leading to bone tissue regeneration. Besides this, we also studied how the mechanical and physical properties of the composites were affected by the two phases and tried to develop a material with as close properties as possible to those of bone tissue.