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Abstract
Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.
Bioresorbable electronic stimulators can deliver electrical stimulation in rodents to enhance functional muscle recovery after nerve injury. Here, the authors present a bioresorbable dynamic covalent polymer that enables reliable, long-lived operation of soft, stretchable devices of this type.
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1 Northwestern University, Center for Bio-Integrated Electronics, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Materials Science and Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
2 University of California, Los Angeles, Department of Bioengineering, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Division of Plastic and Reconstructive Surgery, Department of Surgery, Tainan, Taiwan (GRID:grid.412040.3) (ISNI:0000 0004 0639 0054); National Cheng Kung University, International Research Center for Wound Repair and Regeneration, Tainan, Taiwan (GRID:grid.64523.36) (ISNI:0000 0004 0532 3255)
3 Northwestern University, Center for Bio-Integrated Electronics, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Korea University, School of Biomedical Engineering, Seoul, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678); Korea University, Interdisciplinary Program in Precision Public Health, Seoul, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678)
4 Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Mechanical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
5 Northwestern University, Department of Mechanical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
6 University of California, Los Angeles, Department of Bioengineering, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California, Los Angeles, Department of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
7 University of Technology, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian, Dalian, China (GRID:grid.19006.3e); Dalian University of Technology, Department of Engineering Mechanics, Dalian, China (GRID:grid.30055.33) (ISNI:0000 0000 9247 7930); Dalian University of Technology, International Research Center for Computational Mechanics, Dalian, China (GRID:grid.30055.33) (ISNI:0000 0000 9247 7930)
8 Northwestern University, Center for Bio-Integrated Electronics, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
9 Zhejiang University, State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X)
10 Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Biomedical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
11 Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Materials Science and Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
12 Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
13 Northwestern University, Department of Mechanical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Shanghai Jiao Tong University, State Key Laboratory of Mechanical System and Vibration, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
14 Northwestern University, Center for Developmental Therapeutics, Chemistry Life Processes Institute, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
15 Washington University School of Medicine, Department of Neurological Surgery, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002)
16 Northwestern University, Department of Biomedical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
17 Northwestern University, Center for Advanced Molecular Imaging, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
18 University of California, Los Angeles, Department of Bioengineering, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
19 Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Sungkyunkwan University (SKKU), School of Advanced Materials Science and Engineering, Suwon, Republic of Korea (GRID:grid.264381.a) (ISNI:0000 0001 2181 989X)
20 Northwestern University, Department of Biomedical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Center for Advanced Regenerative Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Surgery, Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
21 Northwestern University, Center for Bio-Integrated Electronics, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Materials Science and Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Mechanical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Civil and Environmental Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
22 Regenerative Neurorehabilitation Laboratory, Biologics, Shirley Ryan AbilityLab, Chicago, USA (GRID:grid.280535.9) (ISNI:0000 0004 0388 0584); Northwestern University, Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, The Ken & Ruth Davee Department of Neurology, Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)
23 Northwestern University, Center for Bio-Integrated Electronics, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Querrey Simpson Institute for Biotechnology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Materials Science and Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Mechanical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Biomedical Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Northwestern University, Department of Neurological Surgery, Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)