466174 Synthesis and Characterization of Hyaluronic Acid and Heparin Thiol-Ene Hydrogels for the Spatial Sequestering of Bioactive Signals

Wednesday, November 16, 2016: 12:48 PM
Golden Gate 3 (Hilton San Francisco Union Square)
Nicole J. Darling and Tatiana Segura, Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA

Polymer scaffolds serve a central role in the field of tissue engineering by directing cellular processes based on the mechanical as well as biochemical properties Hyaluronic acid (HA), a non-sulfated glycosaminoglycan (GAG) distributed throughout connective, epithelial, and neural tissue, plays a role in wound healing and angiogenesis. HA hydrogels are widely utilized to create scaffolds for tissue repair and to study cell behavior in vitro. Though these materials are commonly synthesized via Michael addition chemistry, we have found that these chemistries lead to hydrogels that have local areas of high and low crosslinking as a result of inappropriate mixing and fast gelation kinetics (Figure A). This heterogeneity leads to inconsistent cell behavior through the gel and between gels of the same condition.  To circumvent this limitation, we report on light activated thiol-ene HA hydrogels, which can be thoroughly mixed prior to gelation. In addition, we report on the incorporation of heparin, through the same thiol-ene chemistry allowing for dosing of heparin within an HA gel. Heparin (HP), an important glycosaminoglycan (GAG) capable of sequestering growth factors and protecting them from proteolysis, mediates the spatial presentation of both bound and soluble growth factors in vivo and is utilized here in vitro to control the presentation and release of growth factors. We show synthesis of norbornene-functionalized HA (HA-Norb) and norbornene functionalized heparin (Hep-Norb) (Figure B) using completely aqueous chemistry avoiding the need to transfer HA and Hep to the organic phase. As expected, we find that the initiator type and degree of crosslinking influences the mechanical properties of the gels. We find that the ability to dose in Hep is critical to allow extensive cellular spreading and migration (Figure B) through out the scaffold indicating that through modulating growth factor presentation and retention, we can guide cell behaviour. This new hydrogel material more closely mimics the ECM of tissues with substantial GAG content such as the brain.


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See more of this Session: Hydrogel Biomaterials I
See more of this Group/Topical: Materials Engineering and Sciences Division