Investigating the role of muscle fibers in the early stage of nerve regeneration within a Muscle-in-Vein graft

ABSTRACT: Background: Every year, many people experience a reduced quality of life due to peripheral nerve damage, resulting in significant healthcare costs, with painful neuroma formation as a common drawback following improper nerve regeneration. The Muscle-in-Vein (MIV) technique, consisting of a vein enriched with skeletal muscle fibres, offers a promising approach to nerve repair, in which the vein serves as a conduit, while muscle fibres avoid vein collapse and provide essential growth factors. The MIV-technique advantages include natural axon guidance through muscle fibre basal laminae, enhanced Schwann cell migration, reduced scar formation and a lower incidence of neuroma formation compared to synthetic conduits. This research aims to explore the role of muscle fibres in the early stages of nerve regeneration - an essential yet understudied phase - within the MIV graft in a rat median nerve injury and repair model. Methods: The study was performed in vivo inducing an 8 mm gap in the rat median nerve, subsequently repaired through the Muscle-in-vein technique. Regenerating nerves were harvested at 3-, 7-, 14-, and 21-days post-injury for comprehensive molecular and morphological analyses, with particular emphasis on the vascularization process, identified as an emerging key factor in nerve regeneration. Results: Immunofluorescence data reveal complete macrophage colonization and a well-structured vascularization throughout the entire graft 7 days post-injury. RNA sequencing analysis on early time points further confirms the pathways involved in vasculature development among the most enriched ones and provides insights into the behaviour of specific angiogenesis- associated genes. A deep evaluation of differentially expressed genes suggests that endothelial cell differentiation occurs in the early stages, as confirmed by the expression profiles of subtype-specific endothelial cell markers. Conclusions: Our data supports the hypothesis of a partial anastomosis between the vessels of the nerve stumps and those of the muscle guided by macrophages. This insight enhances our understanding of the MIV technique and provides valuable guidance for improving tissue engineering approaches for developing more effective treatments for peripheral nerve injuries.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE298178 | GEO | 2026/03/30

REPOSITORIES: GEO