Injectable Electroactive Hydrogel Research Articles

An injectable, self-healing, electroconductive hydrogel loaded with neural stem cells and donepezil for enhancing local therapy effect of spinal cord injury

BackgroundSpinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy.MethodsIn this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury.ResultsThe NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction.ConclusionsThe DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.

Fabricating an electroactive injectable hydrogel based on pluronic-chitosan/aniline-pentamer containing angiogenic factor for functional repair of the hippocampus ischemia rat model.

The hippocampus, a critical cerebral region involved in learning and memory formation, is especially vulnerable to ischemic defect. Here, we developed an injectable electroactive hydrogel based on pluronic-chitosan/aniline-pentamer with proper conductivity around 10-4S/cm to achieve the functional repair of the hippocampus following the ischemic defect. FTIR, DSC, and TGA measurements were performed to assess the chemical structure and thermal stability of the synthesized hydrogel. Aniline pentamer decreased the swelling capacity, degradation, and drug release rate. Further, contact angle, melting point, and gelation time of hydrogels were enhanced by addition of aniline oligomer. Moreover, it endowed the on-demand electro-responsive drug release. Injectability of hydrogel was evaluated by rheometry, exhibiting proper gelling time at the body temperature. The ionic/electrical conductivity and desired in vitro biocompatibility with PC12 cells were also achieved. Injection of VEGF-loaded electroactive hydrogel in the hippocampal ischemic animal model resulted in decreased infarction volume, improved hippocampal dependent learning, and memory performance. Taken all together, the results confirmed that fabricated injectable hydrogel would be a suitable candidate for ischemic defect treatment and can lead to new horizons to treat neurological disorders.

Green synthesis of degradable conductive thermosensitive oligopyrrole/chitosan hydrogel intended for cartilage tissue engineering

Electroactive scaffolds containing conductive polymers can promote tissue repair and regeneration. However, these polymers are non-degradable and cannot be removed from body. To overcome this limitation of conductive polymers, we developed a novel injectable electroactive hydrogel containing pyrrole oligomers which possessed the unique properties of being both electrically conductive and biodegradable. First, pyrrole oligomers were synthesized via chemical polymerization and were found to be amorphous with a non-globular morphology. Then, three different compositions of injectable chitosan/beta glycerophosphate hydrogels containing different concentrations of pyrrole oligomers were synthesized and characterized for chemical structure, morphology, conductivity, swelling ratio, In vitro biodegradation and gelation time. An increase in oligopyrrole content resulted in decreased pore size, and increased gelation time, swelling ratio, conductivity and degradation time. Among all the hydrogel compositions, the sample with pyrrole oligomer:chitosan ratio of 0.1 (w/w) showed the most prominent biodegradability, biocompatibility, electro-activity, swelling ratio and pore size values and was chosen as the optimal electroactive hydrogel composition in this work.

Injectable electroactive hydrogels based on Pluronic® F127 and tetraaniline copolymer

Nowadays, injectable electroactive hydrogels have received much attention in biomedical field. In this article, an electroactive copolymer was successfully synthesized by chemical coupling of tetraaniline (TA) onto the chain end of Pluronic® F127. The structure of the resultant copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–vis), and 1H NMR. Cyclic voltammetry (CV) measurements of the copolymer solution indicated good electroactivity. Moreover, the electroactive copolymer showed temperature-responsive sol-gel transitions in aqueous media. Gelation properties of the hydrogels were also studied by rheometer and the results showed that the introduction of TA segment could enhance the mechanical properties of hydrogel. Based on the analyses of 13C NMR spectra and dynamic light scattering (DLS), the sol-gel transition mechanism was attributed to the dehydration of PEG chains in F127. The MTT assay revealed that the TA conjugated F127 copolymer showed excellent biocompatibility. And the copolymer could form gel in vivo at 15min post injection. Therefore, this biocompatible copolymer acted as injectable electroactive hydrogels may have great potential in biomedical uses.

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

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.

Injectable Electroactive Hydrogels Formed via Host-Guest Interactions.

Injectable conducting hydrogels (ICHs) are promising conductive materials in biomedicine and bioengineering fields. However, the synthesis of ICHs in previous work involved chemical cross-linking, and this may result in biocompatibility problems of the hydrogels. We present the successful synthesis of ICHs via noncovalent host-guest interactions, avoiding the side effect of covalent chemical cross-linking. The ICHs are based on the γ-cyclodextrin dimer as the host molecule and tetraaniline and poly(ethylene glycol) as the guests in a synthetic well-defined hydrophilic copolymer. The sol-gel transition mechanism of the in situ hydrogel is thoroughly investigated. This novel synthesis approach of ICHs via supramolecular chemistry will lead to various new biomedical applications for conducting polymers.

In situ electroactive and antioxidant supramolecular hydrogel based on cyclodextrin/copolymer inclusion for tissue engineering repair.

The injectable electroactive and antioxidant hydrogels are prepared from mixing the tetraaniline functional copolymers and α-cyclodextrin (α-CD) aqueous solution. UV-vis and CV of the copolymer solution showed good electroactive properties. The antioxidant ability of the copolymer is also proved. The gelation mechanism and properties of the system are studied by WAXD, DSC, and rheometer. The encapsulated cells are highly viable in the hydrogels, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, H&E staining study suggests acceptable biocompatibility of the materials in vivo. Moreover, data shows the injectable electroactive material can effectively accelerate the proliferation of encapsulated cells with electrical stimuli, and the mechanism is also elaborated. Such an injectable electroactive hydrogel would more closely mimic the native extracellular matrix, thereby combining a biomimetic environment of long-term cell survival and electrical signal to support the generation of functional tissue.

PLA-PEG-PLA and Its Electroactive Tetraaniline Copolymer as Multi-interactive Injectable Hydrogels for Tissue Engineering

Injectable hydrogels have served as biomimic scaffolds that provide a three-dimensional (3D) structure for tissue engineering or carriers for cell encapsulation in the biomedical field. In this study, the injectable electroactive hydrogels (IEHs) were prepared by introducing electrical properties into the injectable materials. Carboxyl-capped tetraaniline (CTA) as functional group was coupled with enantiomeric polylactide-poly(ethylene glycol)-polylactide (PLA-PEG-PLA), and the electroactive hydrogels were obtained by mixing the enantiomeric copolymers of CTA-PLLA-PEG-PLLA-CTA and CTA-PDLA-PEG-PDLA-CTA aqueous solutions. ultraviolet-visible spectroscopy (UV-vis) and cyclic voltammetry (CV) of the complex solution showed good electroactive properties. The gelation mechanism and intermolecular multi-interactions such as stereocomplextion, hydrogen bonding, and π-π stacking were studied by Fourier transform infrared spectroscopy (FT-IR), UV-vis, and wide-angle X-ray diffraction (WAXD). Gelation properties of the complexes were also studied by rheometer. The encapsulated cells remained highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, the gels were formed in situ in the subcutaneous layer, and hematoxylin-eosin (H&E) staining suggested acceptable biocompatibility of our materials in vivo. Moreover, these injectable materials, when treated with pulsed electrical stimuli, were shown to be functionally active and to accelerate the proliferation of encapsulated fibroblasts, cardiomyocytes, and osteoblasts. Hence, the IEHs possessing these excellent properties would be potentially used as in vivo materials for tissue engineering scaffold.