Injectable peptidic hydrogel composites for drug delivery and tissue regeneration applications

The development and growth of new medical therapies is currently closely related to the development of advanced biomaterials that are able to effectively interact and influence biological systems. Such biomaterials are very promising for various biotechnological and biomedical applications, such as drug delivery, tissue engineering, biosensing and tissue regeneration. As far as drug delivery is concerned, the way bioactive molecules are administrated could significantly affect their efficacy and/or stability. An ideal drug delivery system allows to entrap selected molecules, deliver them to the target site and release them in a sustained and controlled way. Controlled release is fundamental to allow a safe and effective drug dosage and to avoid high concentrations in the body. Hydrogels are a class of promising biomaterials for controlled release applications, being composed by a three-dimensional network of nanofibers able to entrap a great amount of water, up to 90-95% of their weight. The network can be originated from the self-assembly of macromolecules or short molecules. The gelation process gives the opportunity to entrap bioactive molecules, previously dissolved in the aqueous phase, thus obtaining hydrogel based materials for drug delivery or tissue engineering applications. Recently the use of short peptides with an aromatic N-group protector (i.e. Fmoc group) has allowed to obtain materials that can effectively self-assemble, in water and mild conditions, in nanofibers by balancing their hydrophobic and hydrophilic counterparts. The use of peptides for biomedical purposes is common because they are biocompatible, cheap, easily prepared and possess high chemical versatility. A limiting factor in the use of these soft materials is given by their low mechanical performance, which could make them too unstable for extensive uses as injectable materials for drug delivery applications. On this basis, and in order to give them appropriate structural stability and sufficient mechanical properties, specific molecular fillers should be added to the native material. We have developed an injectable peptide-based hydrogel composite able to deliver bioactive molecules aiming to promote the regeneration of mammalian osteoarticular tissues. We chose an hydrogel obtained by the self-assembly in water of the peptide hydrogelator Fmoc-Phe3, enzymatically synthesized in water by a lipolytic enzyme, starting from a dipeptide and an Fmoc protected aminoacid. The formed tripeptide molecules self-assemble in water into a three-dimensional fibrous structure. Graphene Oxide (GO) was added in order to improve the stability and mechanical properties of the hydrogel. The effect of GO on the enzymatic synthesis and the self-assembly of Fmoc-Phe3 into self-supporting hydrogels was investigated. Also, we studied in depth the effect of nanocarbon morphology on hydrogel properties (i.e. morphology, viscoelastic properties, stiffness, resistance to an applied stress) [1]. Moreover, with the aim to employ such hydrogel materials in in vivo biotechnological applications, their biocompatibility and ability to activate ROS production by monocytes was tested. Then, we successfully used such composite hydrogel systems to entrap and release human amniotic mesenchymal stromal cell Secretome, that can exert various biological effects, including antiinflammatory effects .