Injectable deferoxamine-loaded microsphere hydrogels for inhibition of ferroptosis and promotion of third-degree burn wound healing

Langjie Chai; Jianglong Huang; Min Wang; Yihui Huang; Zhuo Huang; Ruiyu Zhang; Lu He; Haijie Wang; Danyang Chen; Yifeng Lei; Liang Guo

doi:10.1016/j.mtbio.2025.101806

Injectable deferoxamine-loaded microsphere hydrogels for inhibition of ferroptosis and promotion of third-degree burn wound healing

Mater Today Bio. 2025 Apr 26:32:101806. doi: 10.1016/j.mtbio.2025.101806. eCollection 2025 Jun.

Authors

Langjie Chai¹, Jianglong Huang^{1

2}, Min Wang¹, Yihui Huang¹, Zhuo Huang³, Ruiyu Zhang⁴, Lu He¹, Haijie Wang¹, Danyang Chen¹, Yifeng Lei^{5

6}, Liang Guo¹

Affiliations

¹ Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
² Department of Plastic Surgery, Wuhan Traditional Chinese Medicine Hospital, Wuhan, 430050, China.
³ Laboratory for Vascular Translational Science, INSERM U1148 & Université Paris Cité, 75018, Paris, France.
⁴ Department of Pediatrics, Children's Digital Health and Data Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
⁵ School of Power and Mechanical Engineering & The Institute of Technological Science, Wuhan University, Wuhan, 430072, China.
⁶ Wuhan University Shenzhen Research Institute, Shenzhen, 518057, China.

Abstract

In chronic third-degree burn wounds, high levels of inflammatory factors such as IL-1β lead to ferroptosis in surrounding cells, thereby delaying the healing process of the burn wounds. To promote the healing of such wounds, an injectable DFO@GM-H hydrogel was developed. This hydrogel was prepared by loading deferoxamine (DFO) into gelatin microspheres (GMs), and further crosslinking in a mild reaction. The resulting DFO@GM-H hydrogels demonstrated effective self-healing and injectability, rendering them well-suited for application in irregular burn wounds. DFO@GM-H hydrogels not only maintained a moist healing environment for the burn wound healing, but also exhibited the ability to slowly release DFO, therefore overcoming the limitation of the short half-life of DFO in vivo. With sustained release and enhanced stability of DFO from the injectable hydrogels, DFO@GM-H hydrogels demonstrated excellent biocompatibility, effectively promoted cell proliferation, migration and angiogenesis, showed antibacterial activity, and effectively inhibited cellular ferroptosis both in vitro and in vivo. Consequently, DFO@GM-H hydrogels accelerated the healing of burn wounds in rats via ferroptosis inhibition and enhanced cellular response. Therefore, DFO@GM-H hydrogel is anticipated to emerge as a novel bioactive dressing for the management of burn wounds.

Keywords: Bioactive hydrogel; Burn wounds; Ferroptosis; Gelatin microspheres; Wound healing.