BIOSYNTHESIS, CHARACTERIZATION AND BIOMEDICAL APPLICATIONS OF PEPTIDE-BASED HYDROGELS

In recent years, scientific as well as technological interest in the synthesis of peptide-based hydrogel materials have grown dramatically. Applications of such materials are mostly related to the biomedical field, thanks to their biocompatibility and biodegradability. As it is well known, the solid component of a hydrogel can consist of a polymeric network or a supramolecular structure derived from the self-assembly of oligomers or non-polymeric molecules. The ability to control the assembly of such structures by the application of an external stimulus is extremely valuable. Enzyme-catalyzed reactions can be used as selective biological stimuli to trigger hydrogel assembly. In fact, the use of enzymes for the fabrication of peptide-based hydrogels has become an emerging area of scientific research. Recently, we reported the possibility of using microbial lipases to catalyze the synthesis in water of self-assembling peptides. We employed different lipases to efficiently catalyze peptidic bond formation between F-moc phenylalanine and diphenylalanine in aqueous medium. Such biocatalysts were able to synthesize the reaction product F-moc triphenylalanine, with yields ranging from 15 to 33%. The reaction products (Fmoc peptides) spontaneously self-assembled in water to form fibrils, that became entangled to form a three-dimensional structure of fibers with a diameter of approximately 7 nm, as evidenced by AFM measurements. Macroscopically, a stable, self-supporting hydrogel material was produced. Moreover, the influence of the chirality of the aminoacidic moieties on the structure and properties of the hydrogels was investigated. In fact, D aminoacids are interesting building blocks for biomedical applications as they are more stable in vivo. The viscoelastic properties of the synthesized hydrogels were investigated and their biocompatibility with different mammalian cells was assessed. Such hydrogel materials were used to entrap nanostructured drug delivery systems, with the aim of creating a biomaterial that may support cell growth and differentiation of human gingival fibroblasts (HGFs). The release kinetics of dexamethasone (DXM) from biopolymeric nanoparticles entrapped within the hydrogel was studied, confirming the possibility of using such system for the sustained release of a bioactive molecule that is able to promote HGFs differentiation into osteoblasts. Our results suggest the possibility of using F-moc oligopetides as building blocks for a new class of injectable cell scaffolds that could play an important role in bone regeneration, i.e. to reconstruct anatomical defects caused by cancer surgery, malformations and trauma.