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Grants Funded

ASPS/PSF leadership is committed to continuing to provide high levels of investigator-initiated research support to ensure that plastic surgeons have the needed research resources to be pioneers and innovators in advancing the practice of medicine.

Research Abstracts

Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area or PSF funding mechanism.

Reprogramming Muscle Cells to Motor Neurons to Enhance Recovery Post-Nerve Injury

Principal Investigator
Hamid Malekzadeh MD

Year
2025

Institution
The Ohio State University Wexner Medical Center

Funding Mechanism
Research Fellowship

Focus Area
Tissue Engineering, Technology Based

Abstract
Project Summary

Functional recovery after peripheral nerve injuries (PNIs) is often not complete. Nerve regeneration slowly (~1 mm/day), delaying muscle reinnervation by several months. Furthermore, nerve repair is often postponed due to the need for vascular and orthopedic stabilization, debridement, and infection prevention. This lack of neural input leads to neuromuscular junction (NMJ) degeneration
and irreversible muscle atrophy. The current standard is repair with an autograft, which has limitations including donor site sensory loss, limited graft availability, and increased operative time. These challenges underscore the need for innovative interventions to improve muscle reinnervation and functional recovery.

This study aims to investigate whether reprogramming muscle-resident cells into motor-like neurons can prevent muscle atrophy and NMJ degeneration until nerve supply is restored. We hypothesize that generating iMNs in denervated muscle will accelerate muscle reinnervation and improve motor function following nerve repair. We propose using Tissue Nano-Transfection (TNT), a nonviral technique, to directly reprogram muscle cells into induced motor neurons (iMNs) in denervated muscle. TNT offers a powerful method with the potential to change PNI care, especially for patients presenting months after injury. This study will use direct nerve repair and nerve graft models in mice to test this hypothesis.

By addressing the challenges of prolonged denervation, this research could transform PNI treatment, by extending the window of reinnervation of muscle after PNI , particularly for patients with delayed nerve repair. Our long-term goal is to develop a minimally invasive therapy for treatment of PNIs that enhance muscle reinnervation and motor function by leveraging direct cellular
reprogramming techniques, ultimately improving outcomes for patients with chronic or complex nerve injuries.

Impact Statement

Peripheral nerve injuries frequently lead to life-altering disabilities due to poor motor recovery, even after surgical repair. This study pioneers the use of tissue nano-transfection technology to reprogram muscle cells into motor neurons directly within denervated muscle. By preserving muscle electrophysiologic integrity and enhancing reinnervation, this approach could significantly improve functional outcomes for patients. The findings from this research have the potential to transform peripheral nerve injury management by introducing a novel therapeutic strategy that bridges basic science and clinical application.

Biography
Hamid Malekzadeh, MD, is a Plastic Surgery Research Fellow at The Ohio State University in the Nerve Regeneration Lab. He graduated with honors from medical school in Tehran, Iran. Dr. Malekzadeh’s research has focused on using gene therapy approaches to improve peripheral nerve regeneration by enhancing vascularity, promoting neural regeneration, and inducing immunoprotection in cellular allografts. He previously completed a research fellowship at the University of Pittsburgh, where he studied adipose stem cell aging, radiation-induced skin fibrosis, and ex vivo machine perfusion systems. Dr. Malekzadeh has authored over 20 abstracts and 15 peer-reviewed articles, some of which have been recognized as best presentations in scientific conferences. His work bridges peripheral nerve surgery with tissue engineering, and he is passionate about investigating novel therapeutic strategies for peripheral nerve regeneration. In the future, Dr. Malekzadeh plans to pursue a residency in the field of plastic surgery and ultimately a career as a surgeon-scientist in academic plastic surgery. His goal is to integrate clinical practice with laboratory research to advance the field of nerve regeneration, improve patient care, and contribute to the development of innovative treatments for peripheral nerve injuries.