New nanostructured biomaterials for regenerative medicine

Innovative approaches in tissue engineering and regenerative medicine based on decellularized extracellular matrix (ECM) scaffolds and tissues are quickly growing. ECM proteins are particularly adequate toward tissue regeneration applications, since they are natural biomaterials that can be bio-activated with signalling molecules able to influence cell fate, driving cell responses and tissue regeneration. Indeed, it is well recognized that cells perceive and respond to their microenvironment; the underlying mechanisms are generally complex and sometimes still poorly understood. Carbohydrates, found as complex polysaccharides or conjugated to other structural and functional proteins, are relevant components of the cell environment and cell membrane, contributing to cell interactions at several levels: for example, proteoglycans are a major constituent of the extracellular matrix (ECM) surrounding a cell, and glycosoaminoglycans (GAGs) participate in cell-ECM interactions and mediate cell-cell communications. It is now well recognized that glycans play an essential role in a plethora of biological processes, including cellular adhesion, migration, and differentiation, disease progression, and modulation of immunological responses. Although this relevant role, carbohydrates have been rarely considered as signalling cues for ECM derived scaffold functionalization and activation, due to their complexity in synthetic manipulations. Nevertheless, recent data highlight that they can be promising tools for tissue engineering and regenerative medicine applications. Collagen and elastin, in form of 2D matrices or in their hydrolized forms have been bioactivated with different glycidic epitopes; characterizations and biological evaluations have been made. In particular this neo-glycosylated biomaterials have been tested for their ability to influence cell fate; we found that glucose-functionalized biomaterials are able to drive neuronal differentiation, and sialic acid, depending on the regiochemistry of its glycosidic bond, drives mesenchymal stem cells to differentiate in osteogenic or chondrogenic direction. Inspired by the aggrecan, a natural proteoglycans found in cartilaginous tissues, with a bottlebrush structure, another work has been based on the design and production of a synthetic macromolecule, composed of collagen, as core protein, modified with the natural glycosaminoglycan chondroitin sulfate. Due to the high morbidity of some cartilage and bone diseases, and the difficulty, or impossibility, to restore ailing joints, the synthesis of these macromolecules is interesting and could be useful in cartilage tissue regeneration. The area of hydrogels as biomaterials has also been taken into account. Hydrogels are three-dimensional hydrophilic polymer networks obtained from synthetic and/or natural polymers. They are able to swell and retain a large portion of water when placed in an aqueous solution. We synthesized hydrogels, by using modified gelatin with different functional groups, or gelatin in combination with cross-linking agents. Hydrogels have become increasingly studied as matrices for tissue engineering. This kind of material are able to guarantee a 3D environment for cell culture.