2. Academic Validation
  3. Microenvironment-adaptive nanomedicine MXene promotes flap survival by inhibiting ROS cascade and endothelial pyroptosis

Microenvironment-adaptive nanomedicine MXene promotes flap survival by inhibiting ROS cascade and endothelial pyroptosis

  • J Nanobiotechnology. 2025 Apr 7;23(1):282. doi: 10.1186/s12951-025-03343-9.
Ningning Yang # 1 2 3,  Rongrong Hua # 4,  Yingying Lai # 2 5,  Peijun Zhu # 1,  Jian Ding 6 2 5,  Xianhui Ma 2 5,  Gaoxiang Yu 2 5,  Yiheng Xia 7,  Chao Liang 7,  Weiyang Gao 2 5,  Zhouguang Wang 8 9,  Hongyu Zhang 10 11,  Liangliang Yang 12 13 14,  Kailiang Zhou 15 16 17,  Lu Ge 18 19 20
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 2 Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, 325027, Zhejiang, China.
  • 3 State Key Laboratory of Macromolecular Drugs and Large-Scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
  • 4 School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 5 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
  • 6 Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China.
  • 7 Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China.
  • 8 School of Pharmaceutical Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. wzhouguang@gmail.com.
  • 9 State Key Laboratory of Macromolecular Drugs and Large-Scale Preparation, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. wzhouguang@gmail.com.
  • 10 School of Pharmaceutical Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. st_hyz@126.com.
  • 11 Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China. st_hyz@126.com.
  • 12 Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China. liangliangyangLLL@126.com.
  • 13 School of Pharmaceutical Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. liangliangyangLLL@126.com.
  • 14 Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China. liangliangyangLLL@126.com.
  • 15 Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, 325027, Zhejiang, China. zhoukailiang@wmu.edu.cn.
  • 16 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. zhoukailiang@wmu.edu.cn.
  • 17 Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China. zhoukailiang@wmu.edu.cn.
  • 18 Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China. gelu100466@126.com.
  • 19 School of Pharmaceutical Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. gelu100466@126.com.
  • 20 Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China. gelu100466@126.com.
  • # Contributed equally.
PMID: 40197477 DOI: 10.1186/s12951-025-03343-9
Abstract

In the field of large-area trauma FLAP transplantation, preventing avascular necrosis remains a critical challenge. Key mechanisms for improving FLAP viability include angiogenesis promotion, oxidative stress inhibition, and cell death prevention. Recently, two-dimensional ultrathin Ti3C2TX (MXene) nanosheets have gained attention for their potential contributions to these processes, though MXene's physiological impact on FLAP survival had not been previously investigated. This study is the first to confirm MXene's biological effects on the ischaemic microenvironment post-skin FLAP transplantation. Findings indicated that MXene significantly decreased the necrotic area in ischaemic flaps (37.96% ± 2.00%), with reductions of 30.40% ± 1.86% at 1 mg/mL and 20.19% ± 2.11% at 2 mg/mL in a concentration-dependent manner. Mechanistically, MXene facilitated in situ angiogenesis, mitigated oxidative stress, suppressed pro-inflammatory Pyroptosis, and activated the PI3K-Akt pathway, particularly influencing vascular endothelial cells. Comparative transcriptome analysis of skin tissues with and without MXene treatment provided additional evidence, highlighting mechanisms such as pro-inflammatory Pyroptosis, ROS metabolic processes, endothelial cell proliferation regulation, and PI3K-Akt signaling pathway activation. Overall, MXene demonstrated biological activity, effectively promoting ischaemic flaps survival and presenting a novel strategy for addressing ischaemic necrosis in skin flaps.

Keywords

Angiogenesis; Ischaemic flap; MXene; Oxidative stress; Pyroptosis.

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