3D Vascular Analysis of Regenerative Peripheral Nerve Interfaces Shows Neovasculature in Muscle Core by Day 5 Post Surgery

ABSTRACT Introduction/Aims Regenerative peripheral nerve interfaces (RPNIs) are skeletal muscle autografts that can be used as “bio‐amplifiers” of nerve signals in bionic systems. An RPNI may die if its tissue does not revascularize properly; it is not known exactly how neovascular patterns are established in grafts immediately following surgery. Our research goal was to elucidate this process in 3D to provide insight for improving implantable interface design for RPNIs. Methods Rats received unilateral RPNI surgery using the soleus muscle, and 5 or 10 days post surgery, they received ultrasound imaging of both hindlimbs before sacrifice. Tissue was harvested for micro‐CT imaging of vessels and histology. Results Total tissue volume of the RPNIs was significantly reduced relative to contralateral naïve soleus muscles from Day 5 to Day 10, indicating gradual atrophy ( p < 0.01). RPNI groups on both days had core vascular fractions around 12% compared to ~17% in naïve control muscles. There was an unexplained change in the distribution of vessels from the distal end of the RPNI to the proximal end, with the vascular density increasing from Day 5 to Day 10 in the proximal end ( p = 0.02), but not in the distal end. Discussion We expected the vascular fraction within the RPNIs' core would increase from Day 5 to Day 10 post surgery; but that was not observed via micro‐CT. The change in vessel density from end to end of the RPNIs over time might be influenced by the attachment site of the muscle to the transected nerve.