2. Academic Validation
  3. An organ-conformal, kirigami-structured bioelectronic patch for precise intracellular delivery

An organ-conformal, kirigami-structured bioelectronic patch for precise intracellular delivery

  • Cell. 2026 Feb 19;189(4):1086-1107.e32. doi: 10.1016/j.cell.2025.12.021.
Yuqiong Wang 1,  Lamei Du 2,  Han Wu 3,  Hu Li 4,  Jiaqi Liu 5,  Yongyan Hu 6,  Xinran Jiang 3,  Dedong Yin 7,  Yongcun Hao 8,  Ao Xiao 3,  Yawen Yang 4,  Jingkun Zhou 4,  Long Lin 3,  Feng Chen 9,  Denglin Ye 4,  Yuhui He 10,  Zhixiong Zhao 3,  Baoyu Liu 3,  Kuanming Yao 4,  Xiaohong Wang 11,  Xi Chen 12,  Yihang Tong 3,  Fuqi Yao 3,  Kuan Yang 3,  Hong Sun 3,  Yanzhe Fu 3,  Siqi Wang 13,  Zhaocun Huang 3,  Xinyi Chen 14,  Hao Guo 15,  Shenshen Kong 6,  Shaohua Yang 16,  Wenjing Song 17,  Faheem Ershad 18,  Yang Wang 19,  Li Zhang 20,  Qiuting Zhang 16,  Hao Wu 21,  Ning Li 22,  Wei Rao 11,  Jiebo Li 23,  Li Yang 24,  Xing Chen 25,  Wei Mu 19,  Xinge Yu 26,  Yubo Fan 27,  Cunjiang Yu 28,  Ye Xu 29,  Lingqian Chang 30
Affiliations

Affiliations

  • 1 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Qingdao Research Institute, Beihang University, Qingdao 266100, China; Department of Biomedical Engineering, City University of Hong Kong, Hong Kong 999077, China.
  • 2 School of Mechanical Engineering and Automation, Beihang University, Beijing 102206, China; Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin 300131, China.
  • 3 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
  • 4 Department of Biomedical Engineering, City University of Hong Kong, Hong Kong 999077, China.
  • 5 State Key Laboratory of Molecular Oncology, Department of Breast Surgical Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 6 Laboratory Animal Center, Peking University First Hospital, Beijing 100034, China.
  • 7 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; NHC Key Laboratory of Reproductive Health Engineering Technology Research (NRIFP), National Research Institute for Family Planning, Beijing, 100081, China.
  • 8 MOE Key Laboratory of Micro and Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China.
  • 9 College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China.
  • 10 Department of Urology, China-Japan Friendship Hospital, Beijing 100029, China.
  • 11 State Key Laboratory of Cryogenic Science and Technology and Beijing Key Laboratory of Cryo-biomedical Engineering, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
  • 12 Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
  • 13 Department of General Surgery and Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing 100029, China.
  • 14 Department of Dermatology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 15 Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China.
  • 16 School of Mechanical Engineering and Automation, Beihang University, Beijing 102206, China.
  • 17 Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
  • 18 Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Electrical and Computer Engineering, University of Houston, Houston, TX 77204, USA.
  • 19 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Qingdao Research Institute, Beihang University, Qingdao 266100, China; Key Laboratory of Big Data-Based Precision Medicine, Ministry of Industry and Information Technology, School of Engineering Medicine, Beihang University, Beijing 100191, China.
  • 20 Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong 999077, China.
  • 21 Zhejiang Key Laboratory of Soft Matter Biomedical Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
  • 22 Department of Gynecologic Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 23 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beihang University, Beijing 100191, China.
  • 24 Renal Division, Peking University Institute of Nephrology, Beijing Key Laboratory of Precision Medicine and New drug/Equipment Development for Severe Kidney Disease, Peking University First Hospital, Beijing 100034, China.
  • 25 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Key Laboratory of Big Data-Based Precision Medicine, Ministry of Industry and Information Technology, School of Engineering Medicine, Beihang University, Beijing 100191, China; Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beihang University, Beijing 100191, China.
  • 26 Department of Biomedical Engineering, City University of Hong Kong, Hong Kong 999077, China; Institute of Digital Medicine, City University of Hong Kong, Hong Kong 999077, China. Electronic address: [email protected].
  • 27 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beihang University, Beijing 100191, China. Electronic address: [email protected].
  • 28 Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Materials Science and Engineering, Department of Bioengineering, Department of Mechanical Science and Engineering, Beckman Institute for Advanced Science and Technology, Materials Research Laboratory, Nick Holonyak Micro and Nanotechnology Laboratory, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: [email protected].
  • 29 School of Mechanical Engineering and Automation, Beihang University, Beijing 102206, China; Hangzhou International Innovation Institute, Beihang University, Hangzhou 311115, China. Electronic address: [email protected].
  • 30 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Qingdao Research Institute, Beihang University, Qingdao 266100, China; Key Laboratory of Big Data-Based Precision Medicine, Ministry of Industry and Information Technology, School of Engineering Medicine, Beihang University, Beijing 100191, China; Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beihang University, Beijing 100191, China. Electronic address: [email protected].
PMID: 41605209 DOI: 10.1016/j.cell.2025.12.021
Abstract

Efficient and precise delivery of therapeutics toward target loci of organs is crucial for effective disease therapy. However, conventional devices face remarkable challenges to achieve clinically desirable conformality, spatial controllability, and efficiency, especially to organs with complex anatomies, due to a lack of appropriate mechanical and/or material properties. Here, we report a bioelectronic patch for organ-conformal, kirigami-structured electro-transfection (POCKET) that features high conformality enabled by parametric customization, achieving a theoretically maximum effective coverage area over the target organ. The four-layered POCKET forms a unique nanopore-cell juxtaposition configuration at the tissue-device interface, which induces precise, uniform electro-perforation while expediting intracellular transport of payloads. The high delivery efficiency and precise spatial controllability have been systematically validated with various organs. POCKET-mediated therapeutic delivery achieved organ protection from accumulated DNA damage or ischemia-reperfusion injury, restoring organ functionalities. This work presents a customizable technique with translational value for precise therapy in challenging target organs.

Keywords

bioelectronic pach; conformality; electro-transfection; electroporation; intracellular delivery; ischemia-reperfusion injury; kirigami; ovary gene therapy.

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