A Combinatorial Strategy for Peripheral Nerve Repair Utilizing 3D-Printed Collagen Nerve Guidance Conduits and Photobiomodulation Therapy: A Pilot Study in a Rat Sciatic Nerve Transection Model

BACKGROUND: Nerve guidance conduits (NGCs) are a clinically approved option for peripheral nerve repair but remain ineffective compared with autograft "gold standard" treatment options. A combinatorial approach to conduit-based peripheral nerve repair could improve repair outcomes. Photobiomodulation therapy (PBMT) has shown potential to enhance axonal regeneration, but its efficacy in combination with NGCs requires further evaluation. OBJECTIVE: This pilot study investigated the therapeutic potential of a novel 3D-printed, collagen-based NGC combined with PBMT for peripheral nerve regeneration in a 10 mm rat sciatic nerve injury model. MATERIALS AND METHODS: A total of 36 male, 3-month-old, Sprague-Dawley rats were used in a pre-clinical rat model of peripheral neurotmesis and randomly assigned to one of three groups (N = 12 each): Autograft (control), NGC-PBMT (experimental), and NGC + PBMT (experimental). All groups were further subdivided (N = 6) by recovery period (3 or 6 weeks). Collagen-based NGCs were fabricated via DLP 3D printing and implanted into rats with 10 mm sciatic nerve transections. PBMT treatment was applied transcutaneously every other day at 980 nm for 30 s at 1 W. Gross examination, immunohistochemistry, and immunofluorescence were used to assess biocompatibility, vascularization, and nerve regeneration at 3- and 6-weeks post-surgery. RESULTS: Gross examination revealed no sign of inflammation or immune rejection, with significant neovascularization observed throughout the NGCs. Immunostaining demonstrated nerve regeneration in all groups, with progressive axonal growth from week 3 to 6 in the NGC-PBMT group. However, neither experimental group achieved regeneration comparable to the autograft control. PBMT did not yield significant improvement in regenerative outcomes under the tested parameters. CONCLUSIONS: Altogether, this study provides encouraging preliminary evidence that these novel, 3D-printed NGCs are biocompatible and promote early nerve regeneration after peripheral neurotmesis. While PBMT did not enhance outcomes in this study, further work is needed to optimize light delivery parameters and improve conduit design for enhanced neuroregeneration.