A Novel Approach to Peripheral Nerve Regeneration: Local FK-506 Delivery Using a Reservoir Flap Model

Peripheral nerve injuries can lead to lasting functional impairments, impacting movement and quality of life. FK-506, a widely used immunosuppressant, has demonstrated potential in promoting nerve regeneration in addition to its immunosuppressive effects. This study investigates the use of a local reservoir flap to deliver FK-506 directly to the nerve injury site, aiming to enhance nerve regeneration while minimizing systemic immunosuppression.

Sciatic nerve injuries were surgically induced in 24 rats, which were divided into control, 0.5 mg/kg FK-506 (Exp 1), and 2.0 mg/kg FK-506 (Exp 2) groups. A superficial inferior epigastric artery flap served as a reservoir for FK-506, allowing direct delivery to the injury site. FK-506 was administered intermittently over a 4-week period. Outcomes included the Sciatic Functional Index (SFI), muscle recovery (width and weight), nerve morphology, expression of neurogenic markers such as GDNF, immune cell counts, and body weight.

Exp 1 (0.5 mg/kg) demonstrated significant improvements in SFI, GDNF expression, and muscle width compared to the control and high-dose groups. These findings suggest that FK-506 administration via a reservoir flap, particularly at a lower dose, supports effective nerve regeneration. Additionally, FK-506 treatment did not result in significant changes in immune cell profiles or body weight, indicating minimal systemic effects.

Localized FK-506 administration via a reservoir flap effectively enhances peripheral nerve regeneration and minimizes systemic immunosuppression, making it a promising approach for clinical application in treating peripheral nerve injuries.