Abstract
Electroactive hydrogels could guide the regeneration of nerves and promote their functional recovery. An aniline pentamer-crosslinked chitosan (CS-AP) hydrogel with better electroactivity and degradation was fabricated by the carbodiimide method, and then injected into the repair site of sciatic nerve damage, with its gelation time, tensile strength, and conductivity reaching 35 min, 5.02–6.69 MPa, and from 2.97 × 10−4 to 3.25 × 10−4 S·cm−1, respectively, due to the cross-linkage and well-distribution of AP. There was better cytocompativility of CS-AP hydrogel on nerve cells. The results of the in vivo repair indicated that CS-AP10 hydrogel induced the capillaries formation and the repair of sciatic nerve defect, and re-innervated gastrocnemius muscle in the CS-AP10 group were obviously better than other experimental groups, due to the electroactivity of CS-AP and its degradation into fragments. These results indicated the potential application of CS-AP hydrogel in the regeneration and function recovery of peripheral nerve injury.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Siemionow M, Brzezicki G. Chapter 8: Current techniques and concepts in peripheral nerve repair. International Review of Neurobiology, 2009, 87: 141–172
Zhu H, Shen L, Yang M, et al. Progress in facial reinnervation. Journal of Neurorestoratology, 2021, 9(3): 177–185
Schmidt C E, Leach J B. Neural tissue engineering: strategies for repair and regeneration. Annual Review of Biomedical Engineering, 2003, 5(1): 293–347
Wang Y, Zhang Y, Li X, et al. The progress of biomaterials in peripheral nerve repair and regeneration. Journal of Neurorestoratology, 2020, 8(4): 252–269
Javed R, Ao Q. Nanoparticles in peripheral nerve regeneration: a mini review. Journal of Neurorestoratology, 2022, 10(1): 1–12
Guo B, Ma P X. Conducting polymers for tissue engineering. Biomacromolecules, 2018, 19(6): 1764–1782
Ravichandran R, Sundarrajan S, Venugopal J R, et al. Applications of conducting polymers and their issues in biomedical engineering. Journal of the Royal Society Interface, 2010, 7(Suppl 5): S559–S579
Bendrea A D, Cianga L, Cianga I. Review paper: progress in the field of conducting polymers for tissue engineering applications. Journal of Biomaterials Applications, 2011, 26(1): 3–84
Wu Q, Pan C, Hu Y, et al. Neuroprotective effects of adipose-derived stem cells on ferrous sulfate-induced neurotoxicity. Brain Science Advances, 2021, 7(3): 172–183
Zarrintaj P, Zangene E, Manouchehri S, et al. Conductive biomaterials as nerve conduits: recent advances and future challenges. Applied Materials Today, 2020, 20: 100784
Zare E N, Makvandi P, Ashtari B, et al. Progress in conductive polyaniline-based nanocomposites for biomedical applications: a review. Journal of Medicinal Chemistry, 2020, 63(1): 1–22
Liu J, Kim Y S, Richardson C E, et al. Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals. Science, 2020, 367(6484): 1372–1376
Ma X, Ge J, Li Y, et al. Nanofibrous electroactive scaffolds from a chitosan-grafted-aniline tetramer by electrospinning for tissue engineering. RSC Advances, 2014, 4(26): 13652–13661
Guo B L, Finne-Wistrand A, Albertsson A C. Simple route to size-tunable degradable and electroactive nanoparticles from the self-assembly of conducting coil-rod-coil triblock copolymers. Chemistry of Materials, 2011, 23(17): 4045–4055
Zarrintaj P, Bakhshandeh B, Saeb M R F, et al. Oligoaniline-based conductive biomaterials for tissue engineering. Acta Biomaterialia, 2018, 72: 16–34
Dong R, Zhao X, Guo B, et al. Biocompatible elastic conductive films significantly enhanced myogenic differentiation of myoblast for skeletal muscle regeneration. Biomacromolecules, 2017, 18(9): 2808–2819
Chen J, Yu M, Guo B, et al. Conductive nanofibrous composite scaffolds based on in-situ formed polyaniline nanoparticle and polylactide for bone regeneration. Journal of Colloid and Interface Science, 2018, 514: 517–527
Guo B L, Finne-Wistrand A, Albertsson A C. Enhanced electrical conductivity by macromolecular architecture: hyperbranched electroactive and degradable block copolymers based on poly(ε-caprolactone) and aniline pentamer. Macromolecules, 2010, 43(10): 4472–4480
Zhang L, Wang L, Guo B, et al. Cytocompatible injectable carboxymethyl chitosan/N-isopropylacrylamide hydrogels for localized drug delivery. Carbohydrate Polymers, 2014, 103: 110–118
Li P, Poon Y F, Li W, et al. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nature Materials, 2011, 10(2): 149–156
Bain J R, Mackinnon S E, Hunter D A. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plastic and Reconstructive Surgery, 1989, 83(1): 129–136
Guan H, Xie Z, Zhang P, et al. Synthesis and characterization of biodegradable amphiphilic triblock copolymers containing L-glutamic acid units. Biomacromolecules, 2005, 6(4): 1954–1960
Feng Y Y, Bai S, Li G G, et al. Reprogramming rat astrocytes into neurons using small molecules for cell replacement following intracerebral hemorrhage. Brain Science Advances, 2021, 7(3): 184–198
de Medinaceli L, Freed W J, Wyatt R J. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Experimental Neurology, 1982, 77(3): 634–643
Zong Z, Kimura Y, Takahashi M, et al. Characterization of chemical and solid state structures of acylated chitosans. Polymer, 2000, 41(3): 899–906
Hu J, Huang L, Zhuang X, et al. Electroactive aniline pentamer cross-linking chitosan for stimulation growth of electrically sensitive cells. Biomacromolecules, 2008, 9(10): 2637–2644
Wang X, Sun T, Wang C, et al. 1H NMR determination of the doping level of doped polyaniline. Macromolecular Chemistry and Physics, 2010, 211(16): 1814–1819
Liu Y, Hu J, Zhuang X, et al. Synthesis and characterization of novel biodegradable and electroactive hydrogel based on aniline oligomer and gelatin. Macromolecular Bioscience, 2012, 12(2): 241–250
Chao D, Ma X, Lu X, et al. Design, synthesis and characterization of novel electroactive polyamide with amine-capped aniline pentamer in the main chain via oxidative coupling polymerization. Journal of Applied Polymer Science, 2007, 104(3): 1603–1608
Qazi T H, Rai R, Dippold D, et al. Development and characterization of novel electrically conductive PANI-PGS composites for cardiac tissue engineering applications. Acta Biomaterialia, 2014, 10(6): 2434–2445
Bagheri B, Zarrintaj P, Samadi A, et al. Tissue engineering with electrospun electro-responsive chitosan-aniline oligomer/polyvinyl alcohol. International Journal of Biological Macromolecules, 2020, 147: 160–169
Bagher Z, Atoufi Z, Alizadeh R, et al. Conductive hydrogel based on chitosan-aniline pentamer/gelatin/agarose significantly promoted motor neuron-like cells differentiation of human olfactory ecto-mesenchymal stem cells. Materials Science and Engineering C, 2019, 101: 243–253
Liu S, Wang J, Zhang D, et al. Investigation on cell biocompatible behaviors of polyaniline film fabricated via electroless surface polymerization. Applied Surface Science, 2010, 256(11): 3427–3431
Stoll G, Jander S, Myers R R. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller’s observations to neuroinflammation. Journal of the Peripheral Nervous System, 2002, 7(1): 13–27
Tang X, Xue C, Wang Y, et al. Bridging peripheral nerve defects with a tissue engineered nerve graft composed of an in vitro cultured nerve equivalent and a silk fibroin-based scaffold. Biomaterials, 2012, 33(15): 3860–3867
Kaur G, Adhikari R, Cass P, et al. Electrically conductive polymers and composites for biomedical applications. RSC Advances, 2015, 5(47): 37553–37567
Richardson P M, McGuinness U M, Aguayo A J. Axons from CNS neurons regenerate into PNS grafts. Nature, 1980, 284(5753): 264–265
Schmidt C E, Shastri V R, Vacanti J P, et al. Stimulation of neurite outgrowth using an electrically conducting polymer. Proceedings of the National Academy of Sciences of the United States of America, 1997, 94(17): 8948–8953
Domínguez-Bajo A, González-Mayorga A, Guerrero C R, et al. Myelinated axons and functional blood vessels populate mechanically compliant rGO foams in chronic cervical hemisected rats. Biomaterials, 2019, 192: 461–474
Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature, 2005, 436(7048): 193–200
Xia B, Lv Y. Dual-delivery of VEGF and NGF by emulsion electrospun nanofibrous scaffold for peripheral nerve regeneration. Materials Science and Engineering C, 2018, 82: 253–264
Zhang X, Qi H, Wang S, et al. Cellular responses of aniline oligomers: a preliminary study. Toxicology Research, 2012, 1(3): 201–205
Zhao Y, Wang Y, Gong J, et al. Chitosan degradation products facilitate peripheral nerve regeneration by improving macrophage-constructed microenvironments. Biomaterials, 2017, 134: 64–77
Chen X, Liu C, Huang Z, et al. Preparation of carboxylic graphene oxide-composited polypyrrole conduits and their effect on sciatic nerve repair under electrical stimulation. Journal of Biomedical Materials Research Part A, 2019, 107(12): 2784–2795
Acknowledgements
This work was supported by National Key Research and Development Program of China (Grant No. 2018YFC1106800) and Sichuan Science and Technology Project (Grant No. 2018JY0535).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Miao, D., Li, Y., Huang, Z. et al. Electroactive chitosan-aniline pentamer hydrogel for peripheral nerve regeneration. Front. Mater. Sci. 16, 220614 (2022). https://doi.org/10.1007/s11706-022-0614-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11706-022-0614-8