Impaired voice production holds significant implications for individual health and wellness, social and occupational function, and societal productivity; the societal costs of voice problems in teachers alone have been estimated to be of the order of $2.5 billion annually in the United States. The development of materials for the treatment of vocal fold disorders, however, has been hampered by the stringent mechanical requirements of the vocal fold, which include the ability to both sustain deformation at frequencies as high as 1000Hz, and also completely recoil after transient stretch up to 200%. To date, despite widespread efforts in the development of materials scaffolds for the tissue engineering of the vocal fold, no materials with the required mechanical properties have been identified. We propose a comprehensive bioengineering approach to this problem. We will employ new elastomeric scaffolds based on the insect protein, resilin, which is the primary energy store in the sound-producing, jumping, and flight organs of insects, and demonstrates unmatched resilience (recovery after stretch) after deformation at frequencies up to 4000Hz. We will employ modular recombinant methods to generate resilin- like polypeptides (RLPs) that can be engineered to carry biologically active domains without compromising the mechanical properties of the resilin domain, and in which independent tuning of multiple properties of these matrices, including mechanical properties, cell binding, and degradation, is possible. We will culture human mesenchymal stem cells (hMSCs) in these matrices under both static and dynamic conditions, and employ a suite of oscillatory rheology, tensile testing, and high-frequency torsional-wave methods to characterize the mechanical properties of cell-encapsulated constructs. Histological, immunohistological, western blot, and gene expression techniques will be employed to confirm the differentiation of hMSCs and the production of vocal fold extracellular matrix. These studies will inform our choices of cell/materials constructs for injection into the vocal folds of rabbits to ameliorate vocal fold scarring. Our investigations wil thus contribute to the development of methods to characterize and culture materials at high frequencies, as well as yield a new class of materials that may optimize the regeneration of vocal fold tissue. Our approaches ultimately will be useful as a general platform in the design of materials for mechanically demanding regenerative medicine applications.

Public Health Relevance

Impaired voice production holds significant implications for individual health and wellness, social and occupational function, and societal productivity. In this program, we will develop novel materials for treating vocal fold diseases, based on the protein resilin, which demonstrates key properties similar to those of the vocal fold - excellent recovery after stretch at high frequencies. The development of this novel material, as well as methods to characterize and culture materials at high frequencies, offers a comprehensive approach for mechanically demanding regenerative medicine applications.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
4R01DC011377-05
Application #
9042335
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Shekim, Lana O
Project Start
2012-03-20
Project End
2017-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Delaware
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Li, Linqing; Stiadle, Jeanna M; Levendoski, Elizabeth E et al. (2018) Biocompatibility of injectable resilin-based hydrogels. J Biomed Mater Res A 106:2229-2242
Lau, Hang Kuen; Paul, Alexandra; Sidhu, Ishnoor et al. (2018) Microstructured Elastomer-PEG Hydrogels via Kinetic Capture of Aqueous Liquid-Liquid Phase Separation. Adv Sci (Weinh) 5:1701010
Garcia Garcia, Cristobal; Kiick, Kristi L (2018) Methods for producing microstructured hydrogels for targeted applications in biology. Acta Biomater :
Liang, Yingkai; Li, Linqing; Scott, Rebecca A et al. (2017) Polymeric Biomaterials: Diverse Functions Enabled by Advances in Macromolecular Chemistry. Macromolecules 50:483-502
Hao, Ying; Zerdoum, Aidan B; Stuffer, Alexander J et al. (2016) Biomimetic Hydrogels Incorporating Polymeric Cell-Adhesive Peptide To Promote the 3D Assembly of Tumoroids. Biomacromolecules 17:3750-3760
McGann, Christopher L; Akins, Robert E; Kiick, Kristi L (2016) Resilin-PEG Hybrid Hydrogels Yield Degradable Elastomeric Scaffolds with Heterogeneous Microstructure. Biomacromolecules 17:128-40
Li, Linqing; Stiadle, Jeanna M; Lau, Hang K et al. (2016) Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration. Biomaterials 108:91-110
McGann, Christopher L; Dumm, Rebekah E; Jurusik, Anna K et al. (2016) Thiol-ene Photocrosslinking of Cytocompatible Resilin-Like Polypeptide-PEG Hydrogels. Macromol Biosci 16:129-38
Li, Linqing; Mahara, Atsushi; Tong, Zhixiang et al. (2016) Recombinant Resilin-Based Bioelastomers for Regenerative Medicine Applications. Adv Healthc Mater 5:266-75
Li, Lan; Zhang, Ping; Wang, Wei-Ming et al. (2015) Foldable and Cytocompatible Sol-gel TiO2 Photonics. Sci Rep 5:13832

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