Poly(L-selenomethionine) Hydrogel Reprograming Microenvironments for Full-Thickness Diabetic Chronic Wound Repair

Abstract

Full-thickness repair of chronic wounds poses significant clinical challenges. Although antioxidant and anti-inflammatory effects accelerate the healing of chronic wounds, achieving complete skin regeneration with appendages remains challenging in clinical practice. Herein, a unique selenium-containing thermo-sensitive hydrogel, poly(ethylene glycol)-block-poly(L-selenomethionine) (EG₄₅SeMet₂₅), is designed to reprogram the wound microenvironments and promote skin appendage regeneration in diabetic chronic wounds. EG₄₅SeMet₂₅ forms an injectable sol at room temperature and undergoes a sol-gel transition at body temperature, enabling complete filling of irregular wound defects. Moreover, EG₄₅SeMet₂₅ enhances cell proliferation and effectively scavenges intracellular reactive oxygen species (ROS), thereby exerting cytoprotective effects. Meanwhile, it modulates macrophage polarization to establish a pro-regenerative immune microenvironment. EG₄₅SeMet₂₅ significantly promotes the healing of full-thickness skin wounds in diabetic mice. After 14 d, the remaining unhealed wound area decreases to 2.53% of that in the Control group, accompanied by accelerated angiogenesis and a significant increase in skin appendage formation. In summary, EG₄₅SeMet₂₅ is a promising antioxidant organic selenium hydrogel that not only interrupts the “ROS-inflammation” cycle but also enables functional full-thickness skin repair, offering a unique strategy for treating chronic wounds.

Keywords

Selenium-containing hydrogel / Reactive oxygen species scavenging / Microenvironment reprogramming / Skin appendage regeneration / Diabetic chronic wound

References

[1] Jiang Y, Huang S, Fu X, Liu H, Ran X, Lu S, Hu D, Li Q, Zhang H, Li Y, Wang R, Xie T, Cheng B, Wang L, Liu Y, Ye X, Han C, Chen H. Wound Repair Regen., 2011, 19: 181

[2] Zhang F, Zhang H, Wang S, Gao M, Du K, Chen X, Lu Y, Hu Q, Du A, Du S, Wang J, Shi K, Chen Z, Li Z, Li Z, Xiao J. Nat. Commun., 2025, 16: 3738

[3] Uberoi A, McCready-Vangi A, Grice E A. Nat. Rev. Microbiol., 2024, 22: 507

[4] Adel N, Stankovic N. Plast. Aesthet. Res., 2025, 12: 22

[5] Zhou Q, Zhuang Y, Deng X, Jiang W, Wang X, Yuan C, Lin K. Adv. Mater., 2026, 38: e12719

[6] Falanga V, Isseroff R R, Soulika A M, Romanelli M, Margolis D, Kapp S, Granick M, Harding K. Nat. Rev. Dis. Primers, 2022, 8: 50

[7] Hong Y, Boiti A, Vallone D, Foulkes N S. Antioxidants, 2024, 13: 312

[8] Rodrigues M, Kosaric N, Bonham C A, Gurtner G C. Physiol. Rev., 2019, 99: 665

[9] Hunt M, Torres M, Bachar-Wikstrom E, Wikstrom J D. Commun. Biol., 2024, 7: 1534

[10] Duong T K N, Truong T T, Phan T N L, Nguyen T X, Doan V H M, Vo T T, Choi J, Pal U, Dhar P, Lee B, Oh J, Mondal S. Aggregate, 2025, 6: e70047

[11] Tang Z, Xia Q, Li J, Chen J, Wu X, Li J, Liu J, Liu W, Rong K, Meng X. Biomed. Technol., 2025, 12: 100120

[12] Cong R, Deng C, Li P, Tang Y, Hou J, Zhao J, Wang Q, Chen Y, Tu J, Jiang X, Jiang L. Nat. Commun., 2025, 16: 5797

[13] Zhang H, Liang Q, Ji Y, Chen Q, Jiang W, Zhang D, Wu Y, Yu L, Chen W, Liu R. Bioact. Mater., 2025, 53: 386

[14] Zhang T, Meng Z, Yu H, Ding P, Kai T. Adv. Sci., 2025, 12: 2500696

[15] Xie M, Sun Y, Ding J. Biomater. Sci., 2026, 14: 2575

[16] Wei Y, You W, Li H, Chen J, Tang Z, Luo Y, Xiao W, Yang Q, Feng M, Li L, Wang M. Mater. Today Bio., 2025, 33: 102046

[17] Liu W. Sci. China Technol. Sci., 2025, 68: 2200200

[18] Berthiaume Fox K A, Galvin E R, Kness-Knezinskis E, Hostler A C, Chen K, Gurtner G C. NPJ Biomed. Innov., 2026, 3: 1

[19] Cao H, Duan L, Zhang Y, Cao J, Zhang K. Signal Transduct. Target. Ther., 2021, 6: 426

[20] Weng T, Wu P, Zhang W, Zheng Y, Li Q, Jin R, Chen H, You C, Guo S, Han C, Wang X. J. Transl. Med., 2020, 18: 53

[21] Wang S, Lu H. Polym. Sci. Technol., 2025, 1: 76

[22] Xu Y, Chen J, Ding J, Sun J, Song W, Tang Z, Xiao C, Chen X. Polym. Sci. Technol., 2025, 1: 171

[23] Zhao J, Hu Y, Liu C, Yan C, Liu Z, Chen Z, Nie Z, Xu X, Cui M, Zhao P, Bian L. Adv. Mater., 2026, 38: e72776

[24] Luo Q, Sun J, Li Z, Liu B, Ding J. Chin. Chem. Lett., 2025, 36: 110433

[25] Wang J, Chen M, Zhang Z, Ma L, Chen T. Coord. Chem. Rev., 2023, 493: 215278

[26] Wu L, Yang X, Jia H, Xiao L, Gao C, Hu Z, Wang J, Guo Y, Wang X, Liu T, Cao R, Zhao R C. Adv. Mater., 2024, 36: 2411229

[27] Yampolsky M, Bachelet I, Fuchs Y. Nat. Protoc., 2024, 19: 184

[28] Peña O A, Martin P. Nat. Rev. Mol. Cell Biol., 2024, 25: 599

[29] Huang K, Mi B, Xiong Y, Fu Z, Zhou W, Liu W, Liu G, Dai G. Burns & Trauma, 2025, 13: tkae052

[30] Kim T K, Kim Y J, Min B H, Kim S J. Appl. Microsc., 2014, 44: 15

[31] Zhang X., Yu H., Zhu K., Xiao Y., Gong Y., Che D., Chen W., You G., Yan X., Wang Q., Fan K., Zhou H., Chen G., Nat. Commun., 2026, https://doi.org/10.1038/s41467-026-73672-2.

RIGHTS & PERMISSIONS

Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH