Differential Effects of Calcium Alginate and Carboxymethylcellulose Wound Dressing Extracts on Human Sensory Neuron Regeneration and Secretome.

The peripheral nervous system is critical for wound healing, with sensory nerves releasing neuropeptides that drive tissue repair. Sensory nerve damage impairs healing and contributes to chronic wounds, as observed in diabetic neuropathy. However, the impact of advanced wound dressings on peripheral nerves remains unexplored. Identifying dressings that favour nerve regeneration would aid in managing complex wounds. This study explores the in vitro effects of three wound dressings on sensory neurons: a pure calcium alginate dressing (Alginate), a mixed calcium alginate combined with carboxymethylcellulose dressing and a pure carboxymethylcellulose (CMC) dressing. Sensory neurons from neural progenitors were exposed to dressing extracts for 5 days. Cell viability, neurite regeneration after axotomy and neurite outgrowth from neurospheres were assessed. Neurite extension was evaluated in compartmentalised chips where extracts were restricted to the neurite compartment. Only Alginate was non-cytotoxic across tested concentrations. In the axotomy model, Alginate and CMC preserved neurite regeneration, whereas the mixed dressing impaired regeneration. In neurospheres, Alginate significantly enhanced neurite outgrowth, while CMC had no effect and the mixed dressing inhibited outgrowth. Additionally, Alginate upregulated the secretion of neurotrophic and pro-repair factors, including brain-derived neurotrophic factor and vascular endothelial growth factor, whereas CMC and the mixed dressing mostly down-regulated key factors. Finally, in compartmentalised culture, Alginate tended to enhance neurite extension, while CMC preserved it and the mixed dressing led to regression. These findings suggest that pure calcium alginate dressing supports nerve repair, essential for healing neuropathic wounds and may explain its good clinical performance in complex wounds.