Activation of the TrkA/Ras-MAPK/ERK Signaling Pathway via Carbon Quantum Dot Mimetics for Enhanced Peripheral Nerve Regeneration

Abstract

Peripheral nerve injuries (PNIs) present a significant clinical challenge, often resulting in impaired motor and sensory function. While the peripheral nervous system possesses regenerative capacity, severe injuries necessitate intervention to promote effective recovery. This study investigated the efficacy of novel PCL/Tragacanth scaffolds functionalized with amino acid-modified carbon quantum dots (CQDs) for peripheral nerve regeneration. The CQD was designed to mimic the action of nerve growth factor (NGF) by binding to TrkA receptors and activating the downstream Ras-MAPK/ERK signaling pathway, crucial for neuronal survival and differentiation. In vitro studies using PC12 cells demonstrated that the scaffolds incorporating amino acid-modified CQD significantly enhanced cell viability, neurite outgrowth, and expression of genes associated with neuronal differentiation (c-Jun, ERK1/2). Furthermore, in vivo evaluation in a rat sciatic nerve injury model revealed that these scaffolds promoted axonal regeneration, myelination, and improved motor function recovery, as assessed by the sciatic functional index (SFI). The enhanced regenerative capacity observed with the amino acid-modified CQD-functionalized scaffolds is attributed to their ability to provide sustained activation of the TrkA/Ras-MAPK/ERK signaling pathway, mimicking the beneficial effects of NGF. These findings highlight the potential of this novel biomaterial for developing effective therapeutic strategies for peripheral nerve repair.