The shortcomings of current medical grafting procedures to treat severe bone defects continue to drive the development of alternative therapies. The clinical success of synthetic bone fillers is still disappointingly limited. Although hydrogels have not been classically studied for bone regeneration applications, owing to their inherently low mechanical properties, these highly hydrated soft materials can provide a proper environment to cell adhesion, migration, proliferation and differentiation, thereby mimicking the regulatory function of natural extracellular matrix (ECM). If successfully regenerated, the newly formed bone would comply with the mechanical requirements.
A common feature of mussel-adhesive proteins is the presence of dihydroxyphenylalanine (DOPA), an amino acid formed by posttranslational modification. These proteins adhesive properties can be mimicked by a group of DOPA structurally related molecules, useful for the creation of bioadhesive coatings and hydrogels of great biocompatibility. DOPA-based soft materials can easily incorporate bioactive PEPTIDE molecules. Small peptide mimetics have the ability to reproduce some of the biological roles of biologically related proteins, such as Integrin mediated cell adhesion and capability to induce MINERALIZATION. Thus, intrinsically adhesive and biocompatible hydrogels, which include both cell attachment ligands and prospective hydroxyapatite binding peptides, will be developed to induce the deposition of bone-like mineral in close association with the artificial ECM, under biologically relevant conditions. These artificial ECMs will also incorporate tuned hydrolytically degradable crosslinks, and will be designed to be used as injectable systems for minimally invasive surgical procedures. The overall design aims at creating an artificial ECM that instructs osteogenic and progenitor cells to recapitulate the normal bone healing and morphogenetic processes.
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