Journal of translational medicine · 2026
Delayed repair of singly transected and segmental-loss peripheral nerve injuries in rat sciatic nerves using optimized PEG-fusion protocols and stored viable peripheral nerve allografts.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Olivarez Alexa N, Yang Cathy Z, Zhou Liwen, Mikesh Michelle, Ghergherehchi Cameron L, Garcia Henry A, Schafer Alexander M, Periyasamy Guhan, Nguyen Phuong Vy, Hao Yiming, Agarwal Arjun, Gokhale Varun, Sood Rhea, Nagarajan Neha, Sanklipur Sushant, Bittner George D
Аннотация
BACKGROUND: Singly transected and segmental-loss peripheral nerve injuries (ST- and SL-PNIs) produce immediate loss of sensorimotor functions. Polyethylene glycol (PEG)-fusion repairs performed immediately following ST- and SL-PNIs improve long-term outcomes in animal models, with SL-PNIs repaired using fresh or 1-to-3 day stored viable peripheral nerve allografts (VPNAs). Here, we propose several optimizations for the existing PEG-fusion protocols to repair ST- and SL-PNIs with a delay of 24-48 h post-injury, using longer stored VPNAs for SL-PNIs, both conditions critical for translating PEG-fusion to the clinic.
METHODS: Optimized PEG-fusion protocols to repair ST- and SL-PNIs of the rat sciatic nerve include the additional steps of topical application of low-dose epinephrine and/or local administration of methylprednisolone. Electrophysiological recordings were used to assess the success of surgeries, and Sciatic Functional Index and end-point nerve morphology were performed to assess long-term recovery. For longer VPNA storage, a static storage protocol was established, and the viability of VPNAs was assessed electrophysiologically prior to transplantation and morphologically.
RESULTS: Together, our optimized PEG-fusion and static storage protocols successfully repair ST- and SL-PNIs with a delay of at least 24 h, with SL-PNIs repaired using VPNAs stored for at least 3 weeks. Topical application of low-dose epinephrine stops intraoperative bleeding and improves behavioral recovery. Local administration of methylprednisolone following PEG-fusion eliminates microvasculitis and further improves behavioral recovery.
CONCLUSIONS: The findings in this study using rats, along with the ongoing PEG-fusion clinical trials, suggest the feasibility of clinically translating delayed PEG-fusion repair for ST- or SL-PNIs in humans, and support further investigation into the storage of VPNAs at tissue banks.
METHODS: Optimized PEG-fusion protocols to repair ST- and SL-PNIs of the rat sciatic nerve include the additional steps of topical application of low-dose epinephrine and/or local administration of methylprednisolone. Electrophysiological recordings were used to assess the success of surgeries, and Sciatic Functional Index and end-point nerve morphology were performed to assess long-term recovery. For longer VPNA storage, a static storage protocol was established, and the viability of VPNAs was assessed electrophysiologically prior to transplantation and morphologically.
RESULTS: Together, our optimized PEG-fusion and static storage protocols successfully repair ST- and SL-PNIs with a delay of at least 24 h, with SL-PNIs repaired using VPNAs stored for at least 3 weeks. Topical application of low-dose epinephrine stops intraoperative bleeding and improves behavioral recovery. Local administration of methylprednisolone following PEG-fusion eliminates microvasculitis and further improves behavioral recovery.
CONCLUSIONS: The findings in this study using rats, along with the ongoing PEG-fusion clinical trials, suggest the feasibility of clinically translating delayed PEG-fusion repair for ST- or SL-PNIs in humans, and support further investigation into the storage of VPNAs at tissue banks.