PXL01 alters macrophage response with no effect on axonal outgrowth or Schwann cell response after nerve repair in rats

<b>Background:</b> Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 – a lactoferrin-derived peptide – after repair of the sciatic nerve in healthy Wistar rats. <b>Materials &amp; methods:</b> PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. <b>Results:</b> Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. <b>Conclusion:</b> PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages. Local application of PXL01 decreases inflammation in the injured and immediate repaired nerve without changing the polarization of the macrophages. Local application of PXL01 does not improve or have any negative effect on nerve regeneration. Local application of PXL01 does not alter Schwann cell activity or neuroprotective effect of HSP27 in the injured and repaired nerve or in the sensory neurons. Hyaluronate, the PXL01 vehicle, does not alter nerve regeneration and has no effect on inflammation. CD206, known as antimannose receptor antibody, also stains the paranodal region in the contralateral-uninjured nerve. Results imply that PXL01 treatment can be used to treat scarred and tethered nerves, one of the defined neuromas after surgery, without a negative effect on the regeneration processes.