Imaging-guided bioresorbable acoustic hydrogel microrobots.

Journal: Science robotics
PMID: 39661698

Abstract

Micro- and nanorobots excel in navigating the intricate and often inaccessible areas of the human body, offering immense potential for applications such as disease diagnosis, precision drug delivery, detoxification, and minimally invasive surgery. Despite their promise, practical deployment faces hurdles, including achieving stable propulsion in complex in vivo biological environments, real-time imaging and localization through deep tissue, and precise remote control for targeted therapy and ensuring high therapeutic efficacy. To overcome these obstacles, we introduce a hydrogel-based, imaging-guided, bioresorbable acoustic microrobot (BAM) designed to navigate the human body with high stability. Constructed using two-photon polymerization, a BAM comprises magnetic nanoparticles and therapeutic agents integrated into its hydrogel matrix for precision control and drug delivery. The microrobot features an optimized surface chemistry with a hydrophobic inner layer to substantially enhance microbubble retention in biofluids with multiday functionality and a hydrophilic outer layer to minimize aggregation and promote timely degradation. The dual-opening bubble-trapping cavity design enables a BAM to maintain consistent and efficient acoustic propulsion across a range of biological fluids. Under focused ultrasound stimulation, the entrapped microbubbles oscillate and enhance the contrast for real-time ultrasound imaging, facilitating precise tracking and control of BAM movement through wireless magnetic navigation. Moreover, the hydrolysis-driven biodegradability of BAMs ensures its safe dissolution after treatment, posing no risk of long-term residual harm. Thorough in vitro and in vivo experimental evidence demonstrates the promising capabilities of BAMs in biomedical applications. This approach shows promise for advancing minimally invasive medical interventions and targeted therapeutic delivery.

Authors

  • Hong Han
  • Xiaotian Ma
    School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Weiting Deng
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Junhang Zhang
    Hangzhou Seventh People's Hospital, Affiliated Mental Health Center, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • Songsong Tang
    Department of NanoEngineering and Chemical Engineering Program, University of California San Diego, La Jolla, CA 92093, USA.
  • On Shun Pak
    Department of Mechanical Engineering, Santa Clara University, Santa Clara, CA, 95053, USA. opak@scu.edu.
  • Lailai Zhu
    Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore.
  • Ernesto Criado-Hidalgo
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Chen Gong
    School of Journalism, Fudan University, Shanghai, China.
  • Emil Karshalev
    Department of NanoEngineering , University of California, San Diego , La Jolla , California 92093 , United States.
  • Jounghyun Yoo
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Ming You
  • Ann Liu
    1Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore.
  • Canran Wang
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Hao K Shen
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Payal N Patel
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Claire L Hays
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Peter J Gunnarson
    Graduate Aerospace Laboratories, California Institute of Technology, Pasadena, CA, USA.
  • Lei Li
    Department of Thoracic Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
  • Yang Zhang
    Innovative Institute of Chinese Medicine and Pharmacy, Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • John O Dabiri
    Department of Civil and Environmental Engineering, School of Engineering, Stanford University, Stanford, CA 94305, USA.
  • Lihong V Wang
    Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA. lvw@caltech.edu.
  • Mikhail G Shapiro
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Di Wu
    University of Melbourne, Melbourne, VIC 3010 Australia.
  • Qifa Zhou
    Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
  • Julia R Greer
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
  • Wei Gao
    Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.

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