"Combination of Polyethylene Glycol-Tempol axonal fusion and 3D Bioprinted PCL/GelMA Membrane for Sciatic Nerve Repair in Rats"

• Grant number: 24/09568-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Lynn Ana Flavia Salamanca Guillen
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Peripheral nerve transection is a common clinical problem that affects millions of patients each year and requires surgical repair usually carried out by end-to-end neurorrhaphy. However, neuropathic pain, paralysis, and muscle weakness may persist for several months or even become permanent. After neurotmesis, Wallerian degeneration (WD) takes place in the distal stump, and axonal regeneration is slow and partial resulting in limited sensorimotor recovery, causing muscle atrophy. A groundbreaking approach, is the axon fusion after injury, using polyethylene glycol (PEG) as a fusogen, that can connect damaged axonal endings, and an antioxidant, methylene blue (MB), avoiding WD, resulting in prompt electrophysiological recovery. Studies have demonstrated that incorporating the antioxidant MB into the PEG fusion protocol enhances both axonal regeneration and behavioral recovery. Similarly, 4-hydroxy-tempo (Tempol), a cyclic nitroxide with potent antioxidant properties, has shown neuroprotective effects in peripheral nerve injuries and beneficial outcomes in animal models of spinal cord injury. Three-dimensional (3D) bioprinting has emerged as a significant advancement in neural engineering. Polycaprolactone (PCL), a synthetic polymer, is widely utilized for nerve conduits due to its excellent mechanical properties, including durability and structural support. However, its biological functionality is limited when compared to hydrogels such as gelatin methacrylate (GelMA), which have been shown to enhance motor function recovery and promote neuronal differentiation. Consequently, the development of a hybrid 3D-printed PCL/GelMA material for nerve repair represents an innovative and minimally explored strategy, offering the potential to combine mechanical strength with superior bioactivity. Following peripheral nerve injury (PNI), growth factors (GFs), such as fibroblast growth factor 2 (FGF-2), play a critical role in facilitating nerve regeneration. This study aims to evaluate the effectiveness of Tempol compared to MB when combined with the PEG fusion protocol. Additionally, it seeks to determine whether integrating a PCL/GelMA nerve construct with FGF-2 into the fusion protocol can provide the mechanical stability and biological properties necessary to enhance nerve regeneration and improve motor function in rats.