2. Academic Validation
  3. Tracing Immunological Interaction in Trimethylamine N-Oxide Hydrogel-Derived Zwitterionic Microenvironment During Promoted Diabetic Wound Regeneration

Tracing Immunological Interaction in Trimethylamine N-Oxide Hydrogel-Derived Zwitterionic Microenvironment During Promoted Diabetic Wound Regeneration

  • Adv Mater. 2024 Jun 17:e2402738. doi: 10.1002/adma.202402738.
Zheng Li 1 2,  Longwei Li 3 4,  Muxin Yue 1 2 5,  Qingyu Peng 6,  Xiong Pu 3 4,  Yongsheng Zhou 1 2
Affiliations

Affiliations

  • 1 Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
  • 2 National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, P. R. China.
  • 3 CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, China.
  • 4 School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 5 Institute of Medical Technology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, P. R. China.
  • 6 School of Mechanical and Material Engineering, North China University of Technology, Beijing, 100144, P. R. China.
PMID: 38885961 DOI: 10.1002/adma.202402738
Abstract

The diabetic wound healing is challenging due to the sabotaged delicate balance of immune regulation via an undetermined pathophysiological mechanism, so it is crucial to decipher multicellular signatures underlying diabetic wound healing and seek therapeutic strategies. Here, this work develops a strategy using novel trimethylamine N-oxide (TMAO)-derived zwitterionic hydrogel to promote diabetic wound healing, and explore the multi-cellular ecosystem around zwitterionic hydrogel, mapping out an overview of different cells in the zwitterionic microenvironment by single-cell RNA Sequencing. The diverse cellular heterogeneity is revealed, highlighting the critical role of macrophage and neutrophils in managing diabetic wound healing. It is found that polyzwitterionic hydrogel can upregulate Ccl3+ macrophages and downregulate S100a9+ neutrophils and facilitate their interactions compared with polyanionic and polycationic hydrogels, validating the underlying effect of zwitterionic microenvironment on the activation of adaptive immune system. Moreover, zwitterionic hydrogel inhibits the formation of neutrophil extracellular traps (NETs) and promotes angiogenesis, thus improving diabetic wound healing. These findings expand the horizons of the sophisticated orchestration of immune systems in zwitterion-directed diabetic wound repair and uncover new strategies of novel immunoregulatory biomaterials.

Keywords

diabetic wound repair; immune regulation; neutrophil extracellular traps; single‐cell RNA sequencing; zwitterionic hydrogel.

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