Abstract: Rapid and bioorthogonal reactions, when combined with modular building blocks of molecular and microscopic dimensions, enable the construction of synthetic matrices with complex structures, controlled heterogeneity and defined biological functions. Using chemically modified hyaluronic acid (HA) carrying complementary functional groups, we have created various HA-based bulk gels, hydrogel particles (HGPs) and HGP-integrated hydrogel networks with tunable mechanical properties and spatio-temporal presentation of biological cues. When self-assembled block copolymer micelles were employed as the microscopic crosslinkers and drug depots, the resultant hydrogels exhibit force-modulated drug release kinetics. HA hydrogels with spatial gradients of stiffness and ligand density have been successfully synthesized via a diffusion-controlled interfacial crosslinking process without using any templates or external triggers. The enabling chemistry is the cycloaddition of s-tetrazine (TET) with trans-cyclooctene (TCO) derivatives, a biocompatible and bioorthogonal reaction that proceeds with exceptional rates. Separately, protein-mimetic multiblock hybrid polymers have been synthesized by copper (I) catalyzed alyne-azide cycloaddition reaction. These hybrid copolymers exhibit unique assembly characteristics and elastomeric properties. Finally, high molecular weight multiblock copolymers are produced as robust polymer microfibers via interfacial bioorthogonal polymerization employing TET and TCO-functionalized precursors at the oil/water interface. When cell-adhesive peptide is incorporated in the TET monomer, the resulting protein-mimetic polymer fibers provide guidance cues for cell attachment and elongation. The modular approaches allow facile substitution of the constituent building blocks to fine-tune the materials properties for applications in tissue engineering.
Date of update September 29, 2015