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

被引:105
作者
De France, Kevin J. [1 ]
Yager, Kevin G. [2 ]
Chan, Katelyn J. W. [1 ]
Corbett, Brandon [1 ]
Cranston, Emily D. [1 ]
Hoare, Todd [1 ]
机构
[1] McMaster Univ, Dept Chem Engn, 1280 Main St West, Hamilton, ON L8S 4L8, Canada
[2] Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA
基金
加拿大自然科学与工程研究理事会;
关键词
Muscle tissue engineering; cellulose nanocrystals; anisotropic hydrogels; injectable hydrogels; magnetic alignment; nanocomposite biomaterials; POLY(ETHYLENE GLYCOL); MECHANICAL-PROPERTIES; DRUG-DELIVERY; CELLULOSE NANOWHISKERS; RESPONSIVE HYDROGELS; MUSCLE; BIOMATERIALS; MORPHOLOGY; NETWORKS; DIFFERENTIATION;
D O I
10.1021/acs.nanolett.7b03600
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:6487 / 6495
页数:9
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