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Title: Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes

Here, while injectable in situ cross-linking hydrogels have attracted increasing attention as minimally invasive tissue scaffolds and controlled delivery systems, their inherently disorganized and isotropic network structure limits their utility in engineering oriented biological tissues. Traditional methods to prepare anisotropic hydrogels are not easily translatable to injectable systems given the need for external equipment to direct anisotropic gel fabrication and/or the required use of temperatures or solvents incompatible with biological systems. Herein, we report a new class of injectable nanocomposite hydrogels based on hydrazone cross-linked poly(oligoethylene glycol methacrylate) and magnetically aligned cellulose nanocrystals (CNCs) capable of encapsulating skeletal muscle myoblasts and promoting their differentiation into highly oriented myotubes in situ. CNC alignment occurs on the same time scale as network gelation and remains fixed after the removal of the magnetic field, enabling concurrent CNC orientation and hydrogel injection. The aligned hydrogels show mechanical and swelling profiles that can be rationally modulated by the degree of CNC alignment and can direct myotube alignment both in two- and three-dimensions following coinjection of the myoblasts with the gel precursor components. As such, these hydrogels represent a critical advancement in anisotropic biomimetic scaffolds that can be generated noninvasively in vivo following simple injection.
Authors:
ORCiD logo [1] ; ORCiD logo [2] ;  [1] ;  [1] ; ORCiD logo [1] ; ORCiD logo [1]
  1. McMaster Univ., Hamilton, ON (Canada)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)
Publication Date:
Report Number(s):
BNL-114810-2017-JA
Journal ID: ISSN 1530-6984; KC0403020; TRN: US1800365
Grant/Contract Number:
SC0012704
Type:
Accepted Manuscript
Journal Name:
Nano Letters
Additional Journal Information:
Journal Volume: 17; Journal Issue: 10; Journal ID: ISSN 1530-6984
Publisher:
American Chemical Society
Research Org:
Brookhaven National Lab. (BNL), Upton, NY (United States). Center for Functional Nanomaterials (CFN)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; x-ray scattering; hydrogel; Center for Functional Nanomaterials; anisotropic hydrogels; cellulose nanocrystals; injectable hydrogels; magnetic alignment; Muscle tissue engineering; nanocomposite biomaterials
OSTI Identifier:
1412786

De France, Kevin J., Yager, Kevin G., Chan, Katelyn J. W., Corbett, Brandon, Cranston, Emily D., and Hoare, Todd. Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes. United States: N. p., Web. doi:10.1021/acs.nanolett.7b03600.
De France, Kevin J., Yager, Kevin G., Chan, Katelyn J. W., Corbett, Brandon, Cranston, Emily D., & Hoare, Todd. Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes. United States. doi:10.1021/acs.nanolett.7b03600.
De France, Kevin J., Yager, Kevin G., Chan, Katelyn J. W., Corbett, Brandon, Cranston, Emily D., and Hoare, Todd. 2017. "Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes". United States. doi:10.1021/acs.nanolett.7b03600. https://www.osti.gov/servlets/purl/1412786.
@article{osti_1412786,
title = {Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes},
author = {De France, Kevin J. and Yager, Kevin G. and Chan, Katelyn J. W. and Corbett, Brandon and Cranston, Emily D. and Hoare, Todd},
abstractNote = {Here, while injectable in situ cross-linking hydrogels have attracted increasing attention as minimally invasive tissue scaffolds and controlled delivery systems, their inherently disorganized and isotropic network structure limits their utility in engineering oriented biological tissues. Traditional methods to prepare anisotropic hydrogels are not easily translatable to injectable systems given the need for external equipment to direct anisotropic gel fabrication and/or the required use of temperatures or solvents incompatible with biological systems. Herein, we report a new class of injectable nanocomposite hydrogels based on hydrazone cross-linked poly(oligoethylene glycol methacrylate) and magnetically aligned cellulose nanocrystals (CNCs) capable of encapsulating skeletal muscle myoblasts and promoting their differentiation into highly oriented myotubes in situ. CNC alignment occurs on the same time scale as network gelation and remains fixed after the removal of the magnetic field, enabling concurrent CNC orientation and hydrogel injection. The aligned hydrogels show mechanical and swelling profiles that can be rationally modulated by the degree of CNC alignment and can direct myotube alignment both in two- and three-dimensions following coinjection of the myoblasts with the gel precursor components. As such, these hydrogels represent a critical advancement in anisotropic biomimetic scaffolds that can be generated noninvasively in vivo following simple injection.},
doi = {10.1021/acs.nanolett.7b03600},
journal = {Nano Letters},
number = 10,
volume = 17,
place = {United States},
year = {2017},
month = {9}
}