Injectable, degradable, electroactive nanocomposite hydrogels containing conductive polymer nanoparticles for biomedical applications

Abstract

Injectable electroactive hydrogels (eGels) are promising in regenerative medicine and drug delivery, however, it is still a challenge to obtain such hydrogels simultaneously possessing other properties including uniform structure, degradability, robustness, and biocompatibility. An emerging strategy to endow hydrogels with desirable properties is to incorporate functional nanoparticles in their network. Herein, we report the synthesis and characterization of an injectable hydrogel based on oxidized alginate (OA) crosslinking gelatin reinforced by electroactive tetraaniline-graft-OA nanoparticles (nEOAs), where nEOAs are expected to impart electroactivity besides reinforcement without significantly degrading the other properties of hydrogels. Assays of transmission electron microscopy, ¹H nuclear magnetic resonance, and dynamic light scattering reveal that EOA can spontaneously and quickly self-assemble into robust nanoparticles in water, and this nanoparticle structure can be kept at pH 3~9. Measurement of the gel time by rheometer and the stir bar method confirms the formation of the eGels, and their gel time is dependent on the weight content of nEOAs. As expected, adding nEOAs to hydrogels does not cause the phase separation (scanning electron microscopy observation), but it improves mechanical strength up to ~8 kPa and conductivity up to ~10⁻⁶ S/cm in our studied range. Incubating eGels in phosphate-buffered saline leads to their further swelling with an increase of water content <6% and gradual degradation. When growing mesenchymal stem cells on eGels with nEOA content ≤14%, the growth curves and morphology of cells were found to be similar to that on tissue culture plastic; when implanting these eGels on a chick chorioallantoic membrane for 1 week, mild inflammation response appeared without any other structural changes, indicating their good in vitro and in vivo biocompatibility. With injectability, uniformity, degradability, electroactivity, relative robustness, and biocompatibility, these eGels may have a huge potential as scaffolds for tissue regeneration and matrix for stimuli responsive drug release.

Keywords:

• injectability
• electroactivity
• nanocomposite hydrogels
• reinforcement
• tetraaniline
• alginate
• gelatin

Acknowledgments

We would like to thank Professor Huilan Rao from Cancer Center, Sun Yat-sen University, People’s Republic of China for her help in histological analysis, Mr Ruoyao Zhou from Okemos High School, USA for his help in English checking of this manuscript, and Professor Wenge Yao from Guangdong University of Finance, People’s Republic of China for her help in statistical analysis. This work was supported by the National Science Foundation of China (81101153), and the Science and Technology Plan Funds of Guangdong (2009B030801117, 2010B050700012, 2013B051000017).

Disclosure

The authors report no conflicts of interest in this work.