Piezoelectric composite hydrogel with wireless electrical stimulation enhances motor functional recovery of spinal cord injury

doi:10.1016/j.jmst.2023.07.014

Abstract

Abstract: Electrical stimulation (ES) can restore motor function after spinal cord injury (SCI). However, traditional intraspinal ES has many disadvantages, such as the need for a complex circuitry device, an external power source, and a second surgery to remove the implant. Piezoelectric materials have received increasing attention due to their potential to convert ambient mechanical energy into ES without an external power source or implantation of electrodes. Herein, a novel polydopamine (PDA) coated barium titanate (BaTiO₃) nanoparticles (BaTiO₃@PDA) incorporated silk fibroin (SF) hydrogel (SFBT) was established. The SFBT hydrogel was crosslinked by horseradish peroxidase (HRP)/hydrogel peroxide (H₂O₂) to integrate the piezoelectric potency of BaTiO₃ with the thermal sensitivity of HRP/H₂O₂ for SCI recovery. The hydrogel containing 5% (w/v) BaTiO₃@PDA nanoparticles (SFBT-5), which was selected for in vivo study, exhibited a short gelation time (5 min), suitable storage modulus (925 ± 35 Pa), and wireless ES (average current of 124 nA). Moreover, Basso-Beattie-Bresnahan (BBB) scores test and footprint analysis demonstrated that the SFBT-5 hydrogel successfully enhanced motor functional recovery of SCI. In histopathological assessments, the SFBT-5 hydrogel significantly accelerated spinal cord healing, as indicated by smaller lesion cavities (∼16.7% of the SCI group). Meanwhile, the SFBT-5 hydrogel accelerated neurogenesis, facilitated axon regrowth and synapse formation, and promoted remyelination. Overall, this study highlights the potential of piezoelectric hydrogels for SCI regeneration.

Key words: Silk fibroin, Barium titanate, Piezoelectric hydrogel, Spinal cord injury, Electrical stimulation

Zehao Li, Guanlin Li, Xinyu Wang, Zheng Zhao. Piezoelectric composite hydrogel with wireless electrical stimulation enhances motor functional recovery of spinal cord injury[J]. J. Mater. Sci. Technol., 2024, 172: 228-239.

References

[1] J.W. McDonald, C. Sadowsky, Lancet 359 (9304) (2002) 417-425.
[2] C.M. Walsh, J.K. Wychowaniec, D.F. Brougham, D. Dooley, Pharmacol. Ther. 234(2022) 108043.
[3] C. Fan, W. Yang, L. Zhang, H. Cai, Y. Zhuang, Y. Chen, Y. Zhao, J. Dai, Biomateri-als 288 (2022) 121689.
[4] Z. Li, T. Zhao, J. Ding, H. Gu, Q. Wang, Y. Wang, D. Zhang, C. Gao, Bioact. Mater. 19(2023) 550-568.
[5] B. Yang, C. Liang, D. Chen, F. Cheng, Y. Zhang, S. Wang, J. Shu, X. Huang, J. Wang, K. Xia, L. Ying, K. Shi, C. Wang, X. Wang, F. Li, Q. Zhao, Q. Chen, Bioact. Mater. 15(2022) 103-119.
[6] B.Q. Lai, X. Zeng, W.T. Han, M.T. Che, Y. Ding, G. Li, Y.S. Zeng, Biomaterials 279 (2021) 121211.
[7] Y. Tsehay, C. Weber-Levine, T. Kim, A. Chara, S. Alomari, T. Awosika, A. Liu, J. Ehresman, K. Lehner, B. Hwang, A.M. Hersh, I. Suk, E. Curry, F. Aghabaglou, Y. Zeng, A. Manbachi, N. Theodore, Spine J. 22 (8) (2022) 1372-1387.
[8] S. Samejima, R. Henderson, J. Pradarelli, S.E. Mondello, C.T. Moritz, Exp. Neurol. 357(2022) 114178.
[9] A. Higuchi, S. Suresh Kumar, G. Benelli, Q.D. Ling, H.F. Li, A.A. Alarfaj, M.A. Munusamy, T.C. Sung, Y. Chang, K. Murugan, Prog. Mater. Sci. 103(2019) 374-424.
[10] E.A. Kiyotake, M.D. Martin, M.S. Detamore, Acta Biomater. 139(2022) 43-64.
[11] H. Shen, B. Xu, C. Yang, W. Xue, Z. You, X. Wu, D. Ma, D. Shao, K. Leong, J. Dai, Biomaterials 280 (2022) 121279.
[12] L. Li, B. Xiao, J. Mu, Y. Zhang, C. Zhang, H. Cao, R. Chen, H.K. Patra, B. Yang, S. Feng, Y. Tabata, N.K.H. Slater, J. Tang, Y. Shen, J. Gao, ACS Nano 13 (12) (2019) 14283-14293.
[13] X. Yuan, W. Yuan, L. Ding, M. Shi, L. Luo, Y. Wan, J. Oh, Y. Zhou, L. Bian, D.Y.B. Deng, Biomaterials 279 (2021) 121190.
[14] B.A. Karamian, N. Siegel, B. Nourie, M.D. Serruya, R.F. Heary, J.S. Harrop, A.R. Vaccaro, J. Orthop. Traumatol. 23 (1) (2022) 2.
[15] S. Hashimoto, N. Nagoshi, M. Shinozaki, K. Nakanishi, Y. Suematsu, T. Shibata, M. Kawai, T. Kitagawa, K. Ago, Y. Kamata, K. Yasutake, I. Koya, Y. Ando, A. Min-oda, T. Shindo, S. Shibata, M. Matsumoto, M. Nakamura, H. Okano, Biomaterials 295 (2023) 122002.
[16] G. Wei, D. Jiang, S. Hu, Z. Yang, Z. Zhang, W. Li, W. Cai, D. Liu, ACS Appl. Mater. Interfaces 13 (40) (2021) 47341-47353.
[17] Y. Cheng, Y. Xu, Y. Qian, X. Chen, Y. Ouyang, W.E. Yuan, Nano Energy 69 (2020) 104411.
[18] C. Xu, Y. Xu, M. Yang, Y. Chang, A. Nie, Z. Liu, J. Wang, Z. Luo, Adv. Funct. Mater. 30 (39) (2020) 20 0 0177.
[19] I. Goganau, B. Sandner, N. Weidner, K. Fouad, A. Blesch, Exp. Neurol. 300(2018) 247-258.
[20] S. Kandhari, D. Sharma, A.K. Tomar, G. Matis, I.A. Lavrov, P. Majumdar, Respir. Physiol. Neurobiol. 300(2022) 103885.
[21] Q. Yang, A. Ramamurthy, S. Lall, J. Santos, S. Ratnadurai-Giridharan, M. Lopane, N. Zareen, H. Alexander, D. Ryan, J.H. Martin, J.B. Carmel, Exp. Neurol. 320(2019) 112962.
[22] W. Kong, R. Li, P. Xia, S. Pan, Z. Qi, C. Zhao, C. Fu, X. Yang, Mater. Des. 216(2022) 110585.
[23] A. Marino, G.G. Genchi, V. Mattoli, G. Ciofani, Nano Today 14 (2017) 9-12.
[24] K. Kapat, Q.T.H. Shubhra, M. Zhou, S. Leeuwenburgh, Adv. Funct. Mater. 30 (44) (2020) 1909045.
[25] A. Cafarelli, A. Marino, L. Vannozzi, J. Puigmarti-Luis, S. Pane, G. Ciofani, L. Ri-cotti, ACS Nano 15 (2021) 11066.
[26] S. Wu, M.S. Chen, P. Maurel, Y.S. Lee, M.B. Bunge, T.L. Arinzeh, J. Neural. Eng. 15 (5) (2018) 056010.
[27] H. GhaedRahmati, M. Frounchi, S. Dadbin, Mater. Sci. Eng. B 276 (2022) 115535.
[28] B. Fan, Z. Guo, X. Li, S. Li, P. Gao, X. Xiao, J. Wu, C. Shen, Y. Jiao, W. Hou, Bioact. Mater. 5 (4) (2020) 1087-1101.
[29] C. Shuai, G. Liu, Y. Yang, F. Qi, S. Peng, W. Yang, C. He, G. Wang, G. Qian, Nano Energy 74 (2020) 104825.
[30] C. Shuai, G. Liu, Y. Yang, W. Yang, C. He, G. Wang, Z. Liu, F. Qi, S. Peng, Colloids Surf. B 185 (2020) 110587.
[31] C. Xu, Y. Chang, P. Wu, K. Liu, X. Dong, A. Nie, C. Mu, Z. Liu, H. Dai, Z. Luo, Adv. Funct. Mater. 31 (41)(2021) 2104 4 40.
[32] Z. Zhang, X. Zhang, C. Wang, W. Teng, H. Xing, F. Wang, E. Yinwang, H. Sun, Y. Wu, C. Yu, X. Chai, Z. Qian, X. Yu, Z. Ye, X. Wang, Chem. Eng. J. 433(2022) 134465.
[33] F. Huang, T. Chen, J. Chang, C. Zhang, F. Liao, L. Wu, W. Wang, Z. Yin, Int. J. Biol. Macromol. 167(2021) 434-445.
[34] C. Wang, M. Wang, K. Xia, J. Wang, F. Cheng, K. Shi, L. Ying, C. Yu, H. Xu, S. Xiao, C. Liang, F. Li, B. Lei, Q. Chen, Bioact. Mater. 6 (8) (2021) 2523-2534.
[35] A. Raspa, L. Carminati, R. Pugliese, F. Fontana, F. Gelain, J. Control. Rel. 330(2021) 1208-1219.
[36] C.M. Dumont, M.A. Carlson, M.K. Munsell, A.J. Ciciriello, K. Strnadova, J. Park, B.J. Cummings, A.J. Anderson, L.D. Shea, Acta Biomater. 86(2019) 312-322.
[37] Y. Luo, L. Fan, C. Liu, H. Wen, S. Wang, P. Guan, D. Chen, C. Ning, L. Zhou, G. Tan, Bioact. Mater. 7(2022) 98-111.
[38] Z. Qi, T. Zhang, W. Kong, C. Fu, Y. Chang, H. Li, X. Yang, S. Pan, Chem. Eng. J. 427(2022) 130906.
[39] D. Silva, R.A. Sousa, A.J. Salgado, Mater. Today Bio 9 (2021) 10 0 093.
[40] C. Wang, H. Yue, Q. Feng, B. Xu, L. Bian, P. Shi, ACS Appl. Mater. Interfaces 10 (35) (2018) 29299-29307.
[41] S. Chen, S. Liu, L. Zhang, Q. Han, H. Liu, J. Shen, G. Li, L. Zhang, Y. Yang, Chem. Eng. J. 399(2020) 125795.
[42] L. Zhou, Z. Wang, D. Chen, J. Lin, W. Li, S. Guo, R. Wu, X. Zhao, T. Lin, G. Chen, W. Liu, Mater. Des. 217(2022) 110670.
[43] Q. Wang, X. Dong, H. Zhang, P. Li, X. Lu, M. Wu, W. Zhang, X. Lin, Y. Zheng, Y. Mao, J. Zhang, Y. Lin, X. Chen, D. Chen, J. Wang, J. Xiao, Chem. Eng. J. 415(2021) 128964.
[44] L. Wang, Y. Yu, X. Zhao, Z. Zhang, X. Yuan, J. Cao, W. Meng, L. Ye, W. Lin, G. Wang, ACS Appl. Mater. Interfaces 14 (41) (2022) 46273- 46289.
[45] A. Sharma, V. Panwar, B. Mondal, D. Prasher, M.K. Bera, J. Thomas, A. Kumar, N. Kamboj, D. Mandal, D. Ghosh, Nano Energy 99 (2022) 107419.
[46] Y. Zhang, S. Chen, Z. Xiao, X. Liu, C. Wu, K. Wu, A. Liu, D. Wei, J. Sun, L. Zhou, H. Fan, Adv. Healthc. Mater. 10 (16) (2021) e2100695.
[47] Y. Liang, X. Zhao, T. Hu, B. Chen, Z. Yin, P.X. Ma, B. Guo, Small 15 (12) (2019) e190 0 046.
[48] Z. Li, Z. Meng, Z. Zhao, Carbohydr. Polym. 277(2022) 118791.
[49] Z.H. Li, L. Wang, H.L. Dai, X.Y. Wang, J.S. Li, Z. Zhao, J. Supercrit. Fluids 150 (2019) 86-93.
[50] Z. Zheng, M. Li, P. Shi, Y. Gao, J. Ma, Y. Li, L. Huang, Z. Yang, L. Yang, Bioact. Mater. 6 (8) (2021) 2613-2628.
[51] Q. Wang, Y. He, Y. Zhao, H. Xie, Q. Lin, Z. He, X. Wang, J. Li, H. Zhang, C. Wang, F. Gong, X. Li, H. Xu, Q. Ye, J. Xiao, ACS Appl. Mater. Interfaces 9 (8) (2017) 6725-6745.
[52] A. Albashari, Y. He, Y. Zhang, J. Ali, F. Lin, Z. Zheng, K. Zhang, Y. Cao, C. Xu, L. Luo, J. Wang, Q. Ye, ACS Omega 5 (26) (2020) 16064-16075.
[53] W. Man, S. Yang, Z. Cao, J. Lu, X. Kong, X. Sun, L. Zhao, Y. Guo, S. Yao, G. Wang, X. Wang, Biomaterials 276 (2021) 120971.
[54] Y. Sun, C. Yang, X. Zhu, J.J. Wang, X.Y. Liu, X.P. Yang, X.W. An, J. Liang, H.J. Dong, W. Jiang, C. Chen, Z.G. Wang, H.T. Sun, Y. Tu, S. Zhang, F. Chen, X.H. Li, J. Biomed. Mater. Res. A 107 (9) (2019) 1898-1908.