Click-hydrogel delivered aggregation-induced emissive nanovesicles for simultaneous remodeling and antibiosis of deep burn wounds

Abstract

As a high-risk trauma, deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections. In this study, we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties, delivered via a click-chemistry hydrogel. An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl) pyridin-1-ium bromide (THB) with excellent photodynamic properties was first prepared, and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles (THB@ANVs). The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria (up to 100% killing rate), and also beneficial effects on tissue remodeling, including promoting cell migration, cell proliferation, and regulating immunity. In addition, we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds. This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment. In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth, regulating inflammation, promoting early angiogenesis, and collagen deposition. This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.

Keywords

aggregation-induced emission / burn wounds / nanovesicles

References

[1] V. Pavoni, L. Gianesello, L. Paparella, L. T. Buoninsegni, E. Barboni, Scand. J. Trauma Resusc. Emerg. Med. 2010, 18, 24.

[2] Y. Yoshino, M. Ohtsuka, M. Kawaguchi, K. Sakai, A. Hashimoto, M. Hayashi, N. Madokoro, Y. Asano, M. Abe, T. Ishii, T. Isei, T. Ito, Y. Inoue, S. Imafuku, R. Irisawa, M. Ohtsuka, F. Ogawa, T. Kadono, T. Kawakami, R. Kukino, T. Kono, M. Kodera, M. Takahara, M. Tanioka, T. Nakanishi, Y. Nakamura, M. Hasegawa, M. Fujimoto, H. Fujiwara, T. Maekawa, K. Matsuo, O. Yamasaki, A. Le Pavoux, T. Tachibana, H. Ihn, J. Dermatol. 2016, 43, 989.

[3] C. E. Salyer, C. Bomholt, N. Beckmann, C. B. Bergmann, C. A. Plattner, C. C. Caldwell, Surg. Infect. 2021, 22, 113.

[4] M. P. Rowan, L. C. Cancio, E. A. Elster, D. M. Burmeister, L. F. Rose, S. Natesan, R. K. Chan, R. J. Christy, K. K. Chung, Crit. Care 2015, 19, 243.

[5] L. Li, Z. Y. He, X. W. Wei, Y. Q. Wei, Regen. Biomater. 2016, 3, 99.

[6] P. Everts, K. Onishi, P. Jayaram, J. F. Lana, K. Mautner, Int. J. Mol. Sci. 2020, 21, 7794.

[7] Z. Li, P. Maitz, Burns Trauma 2018, 6, 13.

[8] E. Coffin, A. Grangier, G. Perrod, M. Piffoux, I. Marangon, I. Boucenna, A. Berger, L. M’Harzi, J. Assouline, T. Lecomte, A. Chipont, C. Guérin, F. Gazeau, C. Wilhelm, C. Cellier, O. Clément, A. K. A. Silva, G. Rahmi, Nanoscale 2021, 13, 14866.

[9] A. Shpichka, D. Butnaru, E. A. Bezrukov, R. B. Sukhanov, A. Atala, V. Burdukovskii, Y. Zhang, P. Timashev, Stem Cell Res. Ther. 2019, 10, 94.

[10] R. Yang, F. Liu, J. Wang, X. Chen, J. Xie, K. Xiong, Stem Cell Res. Ther. 2019, 10, 229.

[11] X. Sun, W. Song, L. Teng, Y. Huang, J. Liu, Y. Peng, X. Lu, J. Yuan, X. Zhao, Q. Zhao, Y. Xu, J. Shen, X. Peng, L. Ren, Bioact. Mater. 2022, 25, 640.

[12] S. Rani, A. E. Ryan, M. D. Griffin, T. Ritter, Mol. Ther. 2015, 23, 812.

[13] P. Hu, Q. Yang, Q. Wang, C. Shi, D. Wang, U. Armato, I. D. Pra, A. Chiarini, Burns Trauma 2019, 7, 38.

[14] C. Liu, Y. Wang, L. Li, D. He, J. Chi, Q. Li, Y. Wu, Y. Zhao, S. Zhang, L. Wang, Z. Fan, Y. Liao. J. Control. Release 2022, 349, 679.

[15] P. Guo, S. Busatto, J. Huang, G. Morad, M. A. Moses, Adv. Funct. Mater. 2021, 31, 2008326.

[16] H. Wu, X. Jiang, Y. Li, Y. Zhou, T. Zhang, P. Zhi, J. Gao, Adv. Funct. Mater. 2020, 30, 2006169.

[17] C. Hu, T. Lei, Y. Wang, J. Cao, X. Yang, L. Qin, R. Liu, Y. Zhou, F. Tong, C. S. Umeshappa, H. Gao, Biomaterials 2020, 255, 120159.

[18] Y. Wen, Q. Fu, A. Soliwoda, S. Zhang, M. Zheng, W. Mao, Y. Wan, J. Extracell. Vesicles 2022, 1, 100004.

[19] J. Li, H. Zhou, C. Liu, S. Zhang, R. Du, Y. Deng, X. Zou, Aggregate 2023, e359.

[20] B. Li, W. Wang, L. Zhao, D. Yan, X. Li, Q. Gao, J. Zheng, S. Zhou, S. Lai, Y. Feng, J. Zhang, H. Jiang, C. Long, W. Gan, X. Chen, D. Wang, B. Z. Tang, Y. Liao, ACS Nano 2023, 17, 4601.

[21] E. B. Souto, A. F. Ribeiro, M. I. Ferreira, M. C. Teixeira, A. A. M. Shimojo, J. L. Soriano, B. C. Naveros, A. Durazzo, M. Lucarini, S. B. Souto, A. Santini, Int. J. Mol. Sci. 2020, 21, 393.

[22] G. Taubes, Science 2008, 321, 356.

[23] J. Zhang, F. Zhou, Z. He, Y. Pan, S. Zhou, C. Yan, L. Luo, Y. Gao, ACS Appl. Mater. Interface 2022, 14, 30533.

[24] J. Zheng, X. Long, H. Chen, Z. Ji, B. Shu, R. Yue, Y. Liao, S. Ma, K. Qiao, Y. Liu, Y. Liao, Front. Mol. Biosci. 2022, 9, 845179.

[25] J. Sun, H. Li, X. Gu, B. Z. Tang, Adv. Healthc. Mater. 2021, 10, e2101177.

[26] D. Zhu, Y. Duo, M. Suo, Y. Zhao, L. Xia, Z. Zheng, Y. Li, B. Z. Tang, Angew. Chem. Int. Ed. Engl 2020, 59, 13836.

[27] K. Nuutila, E. Eriksson, Adv. Wound Care 2021, 10, 685.

[28] C. Han, D. Jeong, B. Kim, W. Jo, H. Kang, S. Cho, K. H. Kim, J. Park, ACS Biomater. Sci. Eng. 2019, 5, 1534.

[29] Y. Yao, A. Zhang, C. Yuan, X. Chen, Y. Liu, Biomater. Sci. 2021, 9, 4523.

[30] H. Zhang, M. Song, C. Hu, Z. Zhang, S. Zhang, Y. Zhang, Y. Yang, P. Zhou, L. Zheng, L. Li, M. Mao, Y. S. Zhang, P. Ji, X. Zhang, Aggregate 2023, e332.

[31] C. Owh, V. Ow, Q. Lin, J. H. M. Wong, D. Ho, X. J. Loh, K. Xue, Biomater. Adv. 2022, 141, 213100.

[32] E. Coffin, A. Grangier, G. Perrod, M. Piffoux, I. Marangon, I. Boucenna, A. Berger, L. M’Harzi, J. Assouline, T. Lecomte, A. Chipont, C. Guerin, F. Gazeau, C. Wilhelm, C. Cellier, O. Clement, A. K. A. Silva, G. Rahmi, Nanoscale 2021, 13, 14866.

[33] J. Huang, X. Jiang, ACS Appl. Mater. Inter. 2018, 10, 361.

[34] C. Théry, S. Amigorena, G. Raposo, A. Clayton, Curr. Protoc. Cell Biol. 2006, Chapter 3:Unit 3.22, 1.

[35] M. Kang, C. Zhou, S. Wu, B. Yu, Z. Zhang, N. Song, M. M. S. Lee, W. Xu, F. J. Xu, D. Wang, L. Wang, B. Z. Tang, J. Am. Chem. Soc. 2019, 141, 16781.

[36] D. Wang, H. Su, R. T. K. Kwok, X. Hu, H. Zou, Q. Luo, M. M. S. Lee, W. Xu, J. W. Y. Lam, B. Z. Tang, Chem. Sci. 2018, 9, 3685.

[37] J. Sun, Y. Bai, E. Y. Yu, G. Ding, H. Zhang, M. Duan, P. Huang, M. Zhang, H. Jin, R. T. Kwok, Y. Li, G. G. Shan, B. Z. Tang, H. Wang, Biomaterials 2022, 291, 121898.

[38] M. S. Kim, M. J. Haney, Y. Zhao, V. Mahajan, I. Deygen, N. L. Klyachko, E. Inskoe, A. Piroyan, M. Sokolsky, O. Okolie, S. D. Hingtgen, A. V. Kabanov, E. V. Batrakova, Nanomedicine 2016, 12, 655.

[39] Y. Xiong, Y. Xu, F. Zhou, Y. Hu, J. Zhao, Z. Liu, Q. Zhai, S. Qi, Z. Zhang, L. Chen, Bioeng. Transl. Med. 2023, 8, e10373.

[40] H. Zhao, Q. Shang, Z. Pan, Y. Bai, Z. Li, H. Zhang, Q. Zhang, C. Guo, L. Zhang, Q. Wang, J. Diabetes 2018, 67, 235.

[41] X. Bai, J. Li, L. Li, M. Liu, Y. Liu, M. Cao, K. Tao, S. Xie, D. Hu, Front. Immunol. 2020, 11, 1391.

[42] C. Li, S. Wei, Q. Xu, Y. Sun, X. Ning, Z. Wang, Stem Cell Rev. Rep. 2022, 18, 952.

[43] Y. An, S. Lin, X. Tan, S. Zhu, F. Nie, Y. Zhen, L. Gu, C. Zhang, B. Wang, W. Wei, D. Li, J. Wu, Cell Prolif. 2021, 54, e12993.

[44] B. He, J. Zhang, J. Wang, Y. Wu, A. Qin, B. Z. Tang, Macromolecules 2020, 53, 5248.

[45] X. Chen, T. Bai, R. Hu, B. Song, L. Lu, J. Ling, A. Qin, B. Z. Tang, Macromolecules 2020, 53, 2516.

[46] M. He, L. Shi, G. Wang, Z. Cheng, L. Han, X. Zhang, C. Wang, J. Wang, P. Zhou, G. Wang, Int. J. Biol. Macromol. 2020, 155, 1245.

[47] W. Denissen, G. Rivero, R. Nicolaÿ, L. Leibler, J. M. Winne, F. E. D. Prez, Adv. Funct. Mater. 2015, 25, 2451.

[48] Z. Shariatinia, Int. J. Biol. Macromol. 2018, 120, 1406.

[49] S. Mascharak, H. E desJardins-Park, M. F. Davitt, M. Griffin, M. R. Borrelli, A. L. Moore, K. Chen, B. Duoto, M. Chinta, D. S. Foster, A. H. Shen, M. Januszyk, S. H. Kwon, G. Wernig, D. C. Wan, H. P. Lorenz, G. C. Gurtner, M. T. Longaker, Science 2021, 372, eaba2374.

RIGHTS & PERMISSIONS

2023 The Authors. Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.