Remolding Waste Liquid From the Zeolite Synthesis Process Into Wrinkled Dressings for Diabetic Wound Therapeutics With Immunomodulation

Abstract

Chronic wounds resulting from diabetes are among the most common complications in diabetic patients. Attributable to poor local blood circulation and an increased risk of infection, these wounds heal slowly and are difficult to treat, posing a significant global health challenge. Herein, we achieved the green valorization of waste liquid from the natural clay-derived zeolite synthesis process and utilized it to fabricate metal-loaded aluminosilicate dressings with pronounced wrinkled structures (wrinkled Cu–AS, Ga–AS, and Ce–AS) through simple procedures. Wrinkled Cu–AS and Ce–AS exhibited strong antibacterial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans, with wrinkled Ce–AS demonstrating notable antibiotic-like effects against C. albicans. Moreover, wrinkled Ce–AS enhanced hemostatic capability, promoted blood cell aggregation and activation, downregulated inflammatory markers (IL-6/TNFα), stimulated angiogenesis (VEGF), and shifted macrophage polarization toward the M2 phenotype, thereby facilitating rapid wound healing. Sprague–Dawley rats tolerated intraperitoneal administration well, with no observable toxicity as well as satisfactory hemolysis and cell compatibility. Notably, in the context of growing demand for natural clay utilization and zeolite production, this work presents a unique green approach for the efficient reuse of zeolite synthesis waste liquid, offering both environmental sustainability and commercial viability. This expands the repertoire of biomedical materials available for treating chronic diabetic wounds.

Keywords

antimicrobial / diabetic wound healing / kaolinite / M2 macrophage / wrinkled dressing

References

[1] IDF Diabetes Atlas, Diabetes Around the World in 2021. https://diabetesatlas.org/ (accessed March 2025).

[2] C. K. Sen, Adv. Wound Care (New Rochelle) 2021, 10, 281.

[3] W. Ennis, Assessing the Impact of Coronavirus on Wound Care Patients and Practice. https://www.healogics.com/providers/resources/assessing-the-impact-of-coronavirus-on-wound-care-patients-and-practice (accessed March 2025).

[4] K. L. Baquerizo Nole, E. Yim, F. Van Driessche, J. M. Davidson, M. Martins-Green, C. K. Sen, M. Tomic-Canic, R. S. Kirsner, Wound Repair Regen. 2014, 22, 295.

[5] S. Borys, J. Hohendorff, C. Frankfurter, B. Kiec-Wilk, M. T. Malecki, Eur. J. Clin. Investig. 2019, 49, e13067.

[6] J. Feng, Y. Zheng, W. Ma, A. Ihsan, H. Hao, G. Cheng, X. Wang, Pharmacol. Ther. 2023, 252, 108550.

[7] A. May, Z. Kopecki, B. Carney, A. Cowin, ANZ J. Surg. 2022, 92, 379.

[8] M. Ip, S. L. Lui, V. K. M. Poon, I. Lung, A. Burd, J. Med. Microbiol. 2006, 55, 59.

[9] M. Hasanzadeh Kafshgari, W. H. Goldmann, Nanomicro Lett. 2020, 12, 22.

[10] S. Feng, X. Peng, Y. Deng, Y. Luo, S. Shi, X. Wei, X. Pu, X. Yu, ACS Appl. Mater. Interfaces 2024, 16, 59862.

[11] X. Zhai, H. Hu, M. Hu, S. Ji, T. Lei, X. Wang, Z. Zhu, W. Dong, C. Teng, W. Wei, Carbohydr. Polym. 2024, 334, 122064.

[12] L. Qi, Y. Huang, D. Sun, Z. Liu, Y. Jiang, J. Liu, J. Wang, L. Liu, G. Feng, Y. Li, L. Zhang, Small 2024, 20, e2305100.

[13] Y. Li, J. Chen, Q. Xia, J. Shang, Y. He, Z. Li, Y. Chen, F. Gao, X. Yu, Z. Yuan, P. Yin, J. Nanobiotechnol. 2024, 22, 630.

[14] B. Guo, R. Dong, Y. Liang, M. Li, Nat. Rev. Chem. 2021, 5, 773.

[15] K. D. Morrison, S. N. Williams, L. B. Williams, Econ. Geol. 2017, 112, 1551.

[16] L. B. Williams, Clay Clay Miner. 2019, 67, 7.

[17] H. Yao, X. You, Y. Ye, X. Gong, X. Zhang, Y. Wang, X. Zhou, Y. Li, Y. Liu, A. D. Chowdhury, T. Liu, ACS Nano 2024, 18, 30388.

[18] G. Biddeci, G. Spinelli, P. Colomba, F. Di Blasi, Int. J. Mol. Sci. 2022, 23, 11518.

[19] I. Wedmore, J. G. McManus, A. E. Pusateri, J. B. Holcomb, J. Trauma 2006, 60, 655.

[20] R. Cassano, P. Perri, E. Scarcello, P. Piro, R. Sole, F. Curcio, S. Trombino, Polymers 2024, 16, 1770.

[21] X. You, X. Zhang, Y. Ye, H. Zhou, S. Jiang, X. Zhou, A. D. Chowdhury, Dalton Trans. 2023, 52, 14390.

[22] L. Shang, Y. Yan, Z. Li, H. Liu, S. Ge, B. Ma, Adv. Sci. 2024, 11, e2306528.

[23] C. Wang, Y. Lu, P. Chu, T. He, L. Liu, C. Zhang, Sep. Purif. Technol. 2025, 355, 129798.

[24] Y. He, S. Tang, S. Yin, S. Li, J. Clean. Prod. 2021, 306, 127248.

[25] P. Wang, A. Lv, J. Hu, J. a. Xu, G. Lu, Ind. Eng. Chem. Res. 2011, 50, 12741.

[26] K. Shen, W. Qian, N. Wang, J. Zhang, F. Wei, J. Mater. Chem. A 2013, 1, 3272.

[27] Y. Wang, J. Zhang, X. Meng, S. Han, Q. Zhu, N. Sheng, L. Wang, F. Xiao, Microporous Mesoporous Mater. 2019, 286, 105.

[28] Q. Wu, X. Meng, X. Gao, F. Xiao, Acc. Chem. Res. 2018, 51, 1396.

[29] W. Li, E. S. Thian, M. Wang, Z. Wang, L. Ren, Adv. Sci. 2021, 8, e2100368.

[30] A. J. Schwanke, D. R. Silveira, B. M. Saorin Puton, R. L. Cansian, K. Bernardo-Gusmão, J. Clean. Prod. 2022, 338, 130659.

[31] M. I. Binay, S. K. Kirdeciler, B. Akata, Appl. Clay Sci. 2019, 182, 105251.

[32] L. B. Williams, D. W. Metge, D. D. Eberl, R. W. Harvey, A. G. Turner, P. Prapaipong, A. T. Poret-Peterson, Environ. Sci. Technol. 2011, 45, 3768.

[33] Y. Dai, J. Zhang, S. Zhang, L. Li, C. Qu, J. Chen, L. Lu, J. Control. Release 2024, 376, 382.

[34] Z. Hu, J. Shan, X. Jin, W. Sun, L. Cheng, X.-L. Chen, X. Wang, ACS Nano 2024, 18, 24327.

[35] A. H. Phakatkar, V. Yurkiv, P. Ghildiyal, Y. Wang, A. Amiri, L. V. Sorokina, M. R. Zachariah, T. Shokuhfar, R. Shahbazian-Yassar, ACS Nano 2023, 17, 5880.

[36] D. Piñera-Avellaneda, J. Buxadera-Palomero, R. C. Delint, M. J. Dalby, K. V. Burgess, M.-P. Ginebra, E. Rupérez, J. M. Manero, Acta Biomater. 2024, 180, 154.

[37] F. Jiang, Y. Duan, Q. Li, X. Li, Y. Li, Y. Wang, S. Liu, M. Liu, C. Zhang, X. Pan, Carbohydr. Polym. 2024, 334, 122045.

[38] L. Chen, K. Yang, C. Wang, D. Han, J. Wen, Chem. Eng. J. 2024, 495, 153314.

[39] Y. Xue, F. Yang, L. Wu, D. Xia, Y. Liu, Adv. Healthc. Mater. 2024, 13, 2302858.

[40] Y. Qi, K. Qian, J. Chen, Y. E, Y. Shi, H. Li, L. Zhao, J. Nanobiotechnol. 2021, 19, 414.

[41] M. Zhang, X. Zhai, T. Ma, Y. Huang, C. Yan, Y. Du, Chem. Eng. J. 2021, 423, 130301.

[42] N. E. Gordina, V. Y. Prokof'ev, Y. N. Kul'pina, N. V. Petuhova, S. I. Gazahova, O. E. Hmylova, Ultrason. Sonochem. 2016, 33, 210.

[43] T. Hanawa, Sci. Technol. Adv. Mater. 2022, 23, 457.

[44] Q. Wang, Y. Zhao, Z. Shi, X. Sun, T. Bu, C. Zhang, Z. Mao, X. Li, L. Wang, Chem. Eng. J. 2021, 420, 129955.

[45] I. Mitra, S. Bose, W. S. Dernell, N. Dasgupta, C. Eckstrand, J. Herrick, M. J. Yaszemski, S. B. Goodman, A. Bandyopadhyay, Mater. Today 2021, 45, 20.

[46] N. Jiang, Z. Guo, D. Sun, Y. Li, Y. Yang, C. Chen, L. Zhang, S. Zhu, ACS Nano 2018, 12, 7883.

[47] P. Hu, H. Yang, Appl. Clay Sci. 2013, 74, 58.

[48] Z. Khaled, A. Mohsen, A. Soltan, M. Kohail, Ain Shams Eng. J. 2023, 14, 102142.

[49] S. Li, S. Dong, W. Xu, S. Tu, L. Yan, C. Zhao, J. Ding, X. Chen, Adv. Sci. 2018, 5, 1700527.

[50] Y. Shan, F. Cao, X. Zhao, J. Luo, H. Mei, L. Zhang, Y. Huang, Y. Yang, L. Yan, Y. Huang, Y. Han, B. Guo, Biomaterials 2025, 315, 122936.

[51] P. Wang, E. Gao, T. Wang, Y. Feng, Y. Xu, L. Su, W. Gao, Z. Ci, M. R. Younis, J. Chang, C. Yang, L. Duan, J. Nanobiotechnol. 2024, 22, 652.

[52] Y. Yang, Z. Zhong, J. Li, H. Du, Q. Li, X. Zheng, R. Qi, S. Zhang, P. Ren, Z. Li, Appl. Energy 2023, 351, 121829.

[53] Y. Yang, Z. Zhong, J. Li, H. Du, Q. Li, X. Zheng, R. Qi, S. Zhang, Z. Li, Fuel 2023, 332, 126094.

[54] W. Yuan, J. Kuang, M. Yu, Z. Huang, Z. Zou, L. Zhu, J. Hazard. Mater. 2021, 405, 124261.

[55] N. Belmokhtar, H. El Ayadi, M. Ammari, L. Ben Allal, Appl. Clay Sci. 2018,

[56] K. L. Konan, C. Peyratout, J.-P. Bonnet, A. Smith, A. Jacquet, P. Magnoux, P. Ayrault, J. Colloid Interface Sci. 2007, 307, 101.

[57] R. J. P. Lyon, W. M. Tuddenham, Nature 1960, 185, 835.

[58] S. Chandrasekhar, S. Ramaswamy, Appl. Clay Sci. 2022, 21, 133.

[59] K. Liu, T. Shoinkhorova, X. You, X. Gong, X. Zhang, S.-H. Chung, J. Ruiz-Martínez, J. Gascon, A. D. Chowdhury, Dalton Trans. 2024, 53, 11344.

[60] J. Cui, T. Yang, T. Xu, J. Lin, K. Liu, P. Liu, Chin. J. Struct. Chem. 2024, 44, 100438.

[61] B. De Gusseme, G. Du Laing, T. Hennebel, P. Renard, D. Chidambaram, J. P. Fitts, E. Bruneel, I. Van Driessche, K. Verbeken, N. Boon, W. Verstraete, Environ. Sci. Technol. 2010, 44, 6350.

[62] A. A. Alanazi, W. I. A. Saber, M. A. AlDamen, K. M. Elattar, Int. J. Biol. Macromol. 2024, 280, 135862.

[63] G. Kuz'micheva, A. Trigub, A. Rogachev, A. Dorokhov, E. Domoroshchina, Molecules 2024, 29, 4023.

[64] Y. Zhang, M. Luo, X. Shi, A. Li, W. Zhou, Y. Yin, H. Wang, W.-L. Wong, X. Feng, Q. He, Sci. Adv. 2024, 10, eadp4872.

[65] Q. Zhou, K. Li, K. Wang, W. Hong, J. Chen, J. Chai, L. Yu, Z. Si, P. Li, Sci. Adv. 2024, 10, eadp6604.

[66] X. Ji, J. Zhou, Z. Zhou, Z. Liu, L. Yan, Y. Li, H. Guo, W. Su, H. Wang, D. Ni, Bioact. Mater. 2024, 42, 112.

[67] Y. Peng, Y. Guo, X. Ge, Y. Gong, Y. Wang, Z. Ou, G. Luo, R. Zhan, Y. Zhang, J. Nanobiotechnol. 2024, 22, 126.

[68] R. Jayasuriya, K. Ganesan, K. M. Ramkumar, Int. J. Mol. Sci. 2024, 25, 11197.

[69] Z. Li, L. Chen, S. Yang, J. Han, Y. Zheng, Z. Chen, X. Shi, J. Yang, Acta Biomater. 2024, 190, 205.

[70] Z. Wu, W. Wu, C. Zhang, W. Zhang, Y. Li, T. Ding, Z. Fang, J. Jing, X. He, F. Huang, Carbohydr. Polym. 2025, 347, 122740.

[71] C. Lin, Y. Hu, Z. Lin, L. Du, Y. Hu, L. Ouyang, X. Xie, P. Cheng, J. Liao, L. Lu, R. Zeng, P. Xia, Z. Hou, G. Liu, H. Hu, Bioact. Mater. 2025, 43, 240.

[72] C. Jiang, Q. Shi, J. Yang, H. Ren, L. Zhang, S. Chen, J. Si, Y. Liu, D. Sha, B. Xu, J. Ni, J. Adv. Res. 2024, 63, 159.

[73] L. Huang, T. Li, W. Geng, X. Xie, P. Wang, Y. Deng, Y. Gao, D. Bai, T. Tang, C. Cheng, Small 2024, 21, e2407046.

[74] S. He, Z. Li, L. Wang, N. Yao, H. Wen, H. Yuan, J. Zhang, Z. Li, C. Shen, Bioact. Mater. 2024, 35, 17.

RIGHTS & PERMISSIONS

2025 The Author(s). Energy & Environmental Materials published by John Wiley & Sons Australia, Ltd on behalf of Zhengzhou University.