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, 1 H 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.

Synthesis and 3D Printing of Conducting Alginate–Polypyrrole Ionomers

“…Often, a small molar ratio of a polyanion serves as templates to control the morphology of the resulting material, while the bulk of the charge balancing is due to the fact of other anions. In other cases, biopolymers in the form of hydrogels simply form a matrix or template, within which conventional ICP polymers can be grown or deposited [17][18][19]. For example, recent reports have described the formation of cross-linked alginate hydrogels in which PPy or PANI have been electrochemically deposited.…”

“…As the pyrrole monomer is highly water soluble, formation of hydrophilic composites is facile. Previous preparations of ICP/alginate composites have focused primarily on the use of the biopolymer as a template leading to the formation of nanofibers or particles [17,19]. The preparation of a highly polypyrrole-rich polypyrrole/alginate (PPy-ALG) composite for use as an ink for 3D printing has not been explored.…”

Application of minimally invasive injectable conductive hydrogels as stimulating scaffolds for myocardial tissue engineering

“…). ICHs can be prepared through chemical/physical conjugation or simple mechanical mixing . It is believed that an ICH can restore synchronous contraction of the infarcted heart because it can modify the propagation of impulses through the infarcted zone and allow viable myocardium surrounded by the infarcted zone to contract in a suitable timed manner …”

Nanodiamond-based injectable hydrogel for sustained growth factor release: Preparation, characterization and in vitro analysis

“…This design integrates the great advantage of nanoparticles which is the high surface area for adsorption of proteins, along with the ability of the polymeric network to localize the nanoparticles in a target area [16,17]. The choice of a particular nanoparticle can influence the physical and mechanical properties of the hydrogel as well as dictate its ability to retain the loaded growth factor for a prolonged period of time [18].…”