Hyaluronic acid-based microgels for vocal fold regeneration

POLY 277

Xinqiao Jia, xjia@udel.edu1, Yoon Yeo, yoonyeo@mit.edu2, Rodney J. Clifton3, Tong Jiao3, Daniel S. Kohane, dkohane@partners.org4, James Kobler, jkobler@partners.org5, Steven M. Zeitels, zeitels.steven@mgh.harvard.edu5, and Robert Langer, rlanger@mit.edu6. (1) Department of Materials Science and Engineering, University of Delaware, 201 DuPont Hall, Newark, DE 19716, (2) Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., E25/342, Cambridge, MA 02139, (3) Division of Engineering, Brown University, Box D, Providence, RI 02912, (4) Pediatric Intensive Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, (5) Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital, One Bowdoin Square, 11th Floor, Boston, MA 02114, (6) Department of Chemical Engineering and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room E25-342, Cambridge, MA 02139
Vocal fold vibration depends critically on the viscoelasticity of the connective tissue of the vocal fold mucosa. Mechanical stress and deleterious environmental factors can lead to scarring that disrupts the natural pliability of the lamina propria and results in vocal dysfunction. Despite a well-recognized clinical need for a material to replace missing or damaged vibratory connective tissue of the vocal fold, materials have yet to be engineered to meet the mechanical and biological challenges of the tissue. We have developed hyaluronic acid (HA)-based soft hydrogel microspheres (microgels) as an injectable material for vocal fold regeneration. Chemical modification of HA led to the introduction of mutually reactive functional groups (hydrazide HAADH and aldehyde HAALD) along its backbone. Alternatively, polyethylene glycol dialdehyde (PEGDiALD) was employed as in place of HAALD. Simple mixing of the corresponding components resulted in bulk hydrogels that were degraded rapidly in the presence of hyaluronidase. On the other hand, in situ crosslinking within inverse emulsion droplets generated microgels with improved stability and defined functionality. In vitro cytotoxicity studies using vocal fold fibroblasts indicate that microgels synthesized from HAADH/HAALD are essentially non-toxic. The presence of surface functional groups also allows for subsequent crosslinking of the microgels with other reactive polymers, giving rise to macroscopic hydrogels (macrogels) with tunable viscoelasticity. Mechanical measurements indicate that these microgel networks exhibit similar viscoelastic responses as the natural vocal fold lamina propria in the phonation frequency range. The HA-based microgel systems are promising candidates for the treatment of vocal fold scarring.
 

7th International Biorelated Polymers Symposium
1:30 PM-5:10 PM, Monday, 11 September 2006 San Francisco Marriott -- Salon 14/15, Oral

Division of Polymer Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006