Electroactive chitosan-aniline pentamer hydrogel for peripheral nerve regeneration

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.

Graphical abstract

Keywords

peripheral nerve regeneration / chitosan / aniline pentamer / electroactive hydrogel / capillary formation

References

[1] Siemionow M, Brzezicki G . Chapter 8: Current techniques and concepts in peripheral nerve repair. International Review of Neurobiology, 2009, 87 : 141– 172

[2] Zhu H, Shen L, Yang M, , . Progress in facial reinnervation. Journal of Neurorestoratology, 2021, 9( 3): 177– 185

[3] Schmidt C E, Leach J B . Neural tissue engineering: strategies for repair and regeneration. Annual Review of Biomedical Engineering, 2003, 5( 1): 293– 347

[4] Wang Y, Zhang Y, Li X, , . The progress of biomaterials in peripheral nerve repair and regeneration. Journal of Neurorestoratology, 2020, 8( 4): 252– 269

[5] Javed R, Ao Q . Nanoparticles in peripheral nerve regeneration: a mini review. Journal of Neurorestoratology, 2022, 10( 1): 1– 12

[6] Guo B, Ma P X . Conducting polymers for tissue engineering. Biomacromolecules, 2018, 19( 6): 1764– 1782

[7] Ravichandran R, Sundarrajan S, Venugopal J R, , . Applications of conducting polymers and their issues in biomedical engineering. Journal of the Royal Society Interface, 2010, 7( Suppl 5): S559– S579

[8] 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

[9] Wu Q, Pan C, Hu Y, , . Neuroprotective effects of adipose-derived stem cells on ferrous sulfate-induced neurotoxicity. Brain Science Advances, 2021, 7( 3): 172– 183

[10] Zarrintaj P, Zangene E, Manouchehri S, , . Conductive biomaterials as nerve conduits: recent advances and future challenges. Applied Materials Today, 2020, 20 : 100784

[11] Zare E N, Makvandi P, Ashtari B, , . Progress in conductive polyaniline-based nanocomposites for biomedical applications: a review. Journal of Medicinal Chemistry, 2020, 63( 1): 1– 22

[12] Liu J, Kim Y S, Richardson C E, , . Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals. Science, 2020, 367( 6484): 1372– 1376

[13] Ma X, Ge J, Li Y, , . Nanofibrous electroactive scaffolds from a chitosan-grafted-aniline tetramer by electrospinning for tissue engineering. RSC Advances, 2014, 4( 26): 13652– 13661

[14] 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

[15] Zarrintaj P, Bakhshandeh B, Saeb M R F, , . Oligoaniline-based conductive biomaterials for tissue engineering. Acta Biomaterialia, 2018, 72 : 16– 34

[16] Dong R, Zhao X, Guo B, , . Biocompatible elastic conductive films significantly enhanced myogenic differentiation of myoblast for skeletal muscle regeneration. Biomacromolecules, 2017, 18( 9): 2808– 2819

[17] Chen J, Yu M, Guo B, , . 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

[18] 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

[19] Zhang L, Wang L, Guo B, , . Cytocompatible injectable carboxymethyl chitosan/N-isopropylacrylamide hydrogels for localized drug delivery. Carbohydrate Polymers, 2014, 103 : 110– 118

[20] Li P, Poon Y F, Li W, , . A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nature Materials, 2011, 10( 2): 149– 156

[21] 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

[22] Guan H, Xie Z, Zhang P, , . Synthesis and characterization of biodegradable amphiphilic triblock copolymers containing L-glutamic acid units. Biomacromolecules, 2005, 6( 4): 1954– 1960

[23] Feng Y Y, Bai S, Li G G, , . Reprogramming rat astrocytes into neurons using small molecules for cell replacement following intracerebral hemorrhage. Brain Science Advances, 2021, 7( 3): 184– 198

[24] 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

[25] Zong Z, Kimura Y, Takahashi M, , . Characterization of chemical and solid state structures of acylated chitosans. Polymer, 2000, 41( 3): 899– 906

[26] Hu J, Huang L, Zhuang X, , . Electroactive aniline pentamer cross-linking chitosan for stimulation growth of electrically sensitive cells. Biomacromolecules, 2008, 9( 10): 2637– 2644

[27] Wang X, Sun T, Wang C, , . ¹H NMR determination of the doping level of doped polyaniline. Macromolecular Chemistry and Physics, 2010, 211( 16): 1814– 1819

[28] Liu Y, Hu J, Zhuang X, , . Synthesis and characterization of novel biodegradable and electroactive hydrogel based on aniline oligomer and gelatin. Macromolecular Bioscience, 2012, 12( 2): 241– 250

[29] Chao D, Ma X, Lu X, , . 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

[30] Qazi T H, Rai R, Dippold D, , . Development and characterization of novel electrically conductive PANI‒PGS composites for cardiac tissue engineering applications. Acta Biomaterialia, 2014, 10( 6): 2434– 2445

[31] Bagheri B, Zarrintaj P, Samadi A, , . Tissue engineering with electrospun electro-responsive chitosan-aniline oligomer/polyvinyl alcohol. International Journal of Biological Macromolecules, 2020, 147 : 160– 169

[32] Bagher Z, Atoufi Z, Alizadeh R, , . 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

[33] Liu S, Wang J, Zhang D, , . Investigation on cell biocompatible behaviors of polyaniline film fabricated via electroless surface polymerization. Applied Surface Science, 2010, 256( 11): 3427– 3431

[34] 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

[35] Tang X, Xue C, Wang Y, , . 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

[36] Kaur G, Adhikari R, Cass P, , . Electrically conductive polymers and composites for biomedical applications. RSC Advances, 2015, 5( 47): 37553– 37567

[37] Richardson P M, McGuinness U M, Aguayo A J . Axons from CNS neurons regenerate into PNS grafts. Nature, 1980, 284( 5753): 264– 265

[38] Schmidt C E, Shastri V R, Vacanti J P, , . 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

[39] Domínguez-Bajo A, González-Mayorga A, Guerrero C R, , . Myelinated axons and functional blood vessels populate mechanically compliant rGO foams in chronic cervical hemisected rats. Biomaterials, 2019, 192 : 461– 474

[40] Carmeliet P, Tessier-Lavigne M . Common mechanisms of nerve and blood vessel wiring. Nature, 2005, 436( 7048): 193– 200

[41] 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

[42] Zhang X, Qi H, Wang S, , . Cellular responses of aniline oligomers: a preliminary study. Toxicology Research, 2012, 1( 3): 201– 205

[43] Zhao Y, Wang Y, Gong J, , . Chitosan degradation products facilitate peripheral nerve regeneration by improving macrophage-constructed microenvironments. Biomaterials, 2017, 134 : 64– 77

[44] Chen X, Liu C, Huang Z, , . 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

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