Synthesis and Characterization of Hybrid Hydrogels for Use in Vocal Fold Tissue Engineering
Date
2009-05
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Publisher
University of Delaware
Abstract
Vocal fold tissue undergoes a unique set of mechanical stresses and strains. Due to the distinctive nature of this tissue, a synthetic scaffold is needed for vocal fold tissue regeneration. Elastin, a natural and abundant extracellular matrix (ECM) protein, provides native tissue with its strength and elasticity. Therefore, mimicking the copolymer nature of elastin would be beneficial for the synthetic material. In addition, using a hybrid material allows for tuning of biological, morphological, and mechanical properties. To this end, hybrid polymer-peptide materials are attractive candidates because they allow for this repeat architecture and tunability. In this work, synthetic polyethylene glycol (PEG) polymers were linked to peptides with a repeat unit of AKAAAKA via a copper-catalyzed azide-alkyne cycloaddition reaction. Diblock and triblock copolymers were synthesized using azide-functionalized PEG and alkyne functionalized peptide. However, the resulting copolymers failed to form stable hydrogels when treated with amine-reactive crosslinkers. Alternatively, stable hydrogels were obtained by direct cross-linking of functional PEG and peptide building blocks employing click chemistry. It was found that variations in molecular weight, molecular geometry, and functionality of the starting materials had profound effects on the mechanical properties of the resulting hydrogels. Increasing the number of functional groups, or cross-links, increases the stiffness of the material. In order to assess the effect of polymer hydrophobicity on the overall hydrogel mechanical properties, amphiphilic block copolymers based on polycaprolactone (PCL) and PEG were synthesized. The sol-gel-sol transitions of various PCL-PEG-PCL copolymers with varying molecular weights were monitored.
With proper balance of hydrophobic/hydrophilic blocks, the copolymer undergoes phase changes at physiologically relevant temperatures. This research provides critical insight on designing hybrid polymers that mimic the physical and mechanical properties of natural elastin.