Adaptive conductive electrotherapeutic scaffolds for enhanced peripheral nerve regeneration and stimulation

Shriya S Srinivasan; Lisa Gfrerer; Paramesh Karandikar; Avik Som; Amro Alshareef; Sabrina Liu; Haley Higginbotham; Keiko Ishida; Alison Hayward; Sanjeeva P Kalva; Robert Langer; Giovanni Traverso

doi:10.1016/j.medj.2023.05.007

Adaptive conductive electrotherapeutic scaffolds for enhanced peripheral nerve regeneration and stimulation

Med. 2023 Aug 11;4(8):541-553.e5. doi: 10.1016/j.medj.2023.05.007. Epub 2023 Jun 19.

Authors

Affiliations

¹ Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Society of Fellows, Harvard University, Boston, MA 02115, USA. Electronic address: shriyas@mit.edu.
² David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
³ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁵ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁸ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁹ Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁰ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: cgt20@mit.edu.

PMID: 37339635
DOI: 10.1016/j.medj.2023.05.007

Abstract

Background: While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal.

Methods: We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches.

Findings: In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05).

Conclusion: Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models.

Funding: This work was supported by K. Lisa Yang Center for Bionics at MIT.

Keywords: Foundational research; electrical stimulation; lead migration; muscular atrophy; nerve regeneration; nerve repair; nerve stimulation; peripheral nerve; rehabilitation; removable electrodes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Nerve Regeneration / physiology
Sciatic Nerve
Swine
Transcutaneous Electric Nerve Stimulation*
Ultrasonography