Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of diagnostic tool for peripheral nerve injuries

 

In situations of traumatic injury (car-crash, sports injury, combat, etc.) there is a potential to damage nerve tissue leading to localized paralysis. These peripheral nerve injuries are difficult to diagnose under routine physical examination. Recently, researchers at Pennsylvania State University used thermogelling PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to create a gel for delivery of 4-aminopyridine as a diagnosis tool of peripheral nerve injuries. This research holds promise to improve the diagnosis of this severe injury. Read more: Gurjar, Anagha A., Kristen M. Manto, Juan A. Estrada, Marc Kaufman, Dongxiao Sun, Hassan Talukder, and John C. Elfar. "4-Aminopyridine: A Single-Dose Diagnostic Agent to Differentiate Axonal Continuity in Nerve Injuries." Military Medicine 186, no. Supplement_1 (2021): 479-485. https://academic.oup.com/milmed/article-abstract/186/Supplement_1/479/6119423

“ABSTRACT: Introduction: Traumatic peripheral nerve injuries (TPNIs) are increasingly prevalent in battlefield trauma, and the functional recovery with TPNIs depends on axonal continuity. Although the physical examination is the main tool for clinical diagnosis with diagnostic work up, there is no diagnostic tool available to differentiate nerve injuries based on axonal continuity. Therefore, treatment often relies on “watchful waiting,” and this leads to muscle weakness and further reduces the chances of functional recovery. 4-aminopyridine (4-AP) is clinically used in multiple sclerosis patients for walking performance improvement. Preliminary results in conscious mice suggested a diagnostic role of 4-AP in distinguishing axonal continuity. In this study, we thought to evaluate the diagnostic potential of 4-AP on the axonal continuity in unawake/sedated animals. Materials and Methods: Rat sciatic nerve crush and transection injuries were used in this study. Briefly, rats were anesthetized with isoflurane and mechanically ventilated with oxygen-balanced vaporized isoflurane. Sciatic nerve and triceps surae muscles were exposed by blunt dissection, and a stimulating electrode was placed under a sciatic nerve proximal to the crush injury. A force transducer measured muscle tension response to electrical stimulation of sciatic nerve. Muscle response was measured before crush, after crush, and 30 minutes after systemic 4-AP (150 µg/kg) or local (4-AP)-poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG) treatment. Results: We found that both crush and transection injuries in sciatic nerve completely abolished muscle response to electrical stimulation. Single dose of systemic 4-AP and local (4-AP)-PLGA-PEG treatment with crush injury significantly restored muscle responses to electrical stimulation after 30 minutes of administration. However, systemic 4-AP treatment had no effect on muscle response after nerve transection. These results clearly demonstrate that 4-AP can restore nerve conduction and produce muscle response within minutes of administration only when there is a nerve continuity, even in the sedated animal. Conclusions: We conclude that 4-AP could be a promising diagnostic agent in differentiating TPNI based on axonal continuity.”