Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective cases. In repurposing studies, we found that daily systemic administration of the FDA-approved drug 4aminopyridine (4-AP) enhanced functional recovery after acute peripheral nerve injury. This study was aimed at constructing a novel local delivery system of 4-AP using thermogelling polymers. We optimized a thermosensitive (4-AP)−poly(lactide-co-glycolide)−b-poly(ethylene glycol)−b-poly(lactide-co-glycolide) (PLGA−PEG−PLGA) block copolymer formulation. (4-AP)− PLGA−PEG exhibited controlled release of 4-AP both in vitro and in vivo for approximately 3 weeks, with clinically relevant safe serum levels in animals. Rheological investigation showed that (4-AP)−PLGA−PEG underwent a solution to gel transition at 32 °C, a physiologically relevant temperature, allowing us to administer it to an injured limb while subsequently forming an in situ gel. A single local administration of (4-AP)−PLGA−PEG remarkably enhanced motor and sensory functional recovery on post-sciatic nerve crush injury days 1, 3, 7, 14, and 21. Moreover, immunohistochemical studies of injured nerves treated with (4-AP)-PLGA-PEG demonstrated an increased expression of neurofilament heavy chain (NF-H) and myelin protein zero (MPZ) proteins, two major markers of nerve regeneration. These findings demonstrate that (4-AP)−PLGA−PEG may be a promising long-acting local therapeutic agent in TPNI, for which no pharmacologic treatment exists.

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Background The representation of sociodemographic data within randomized-controlled trials (RCT) regarding foot and ankle surgery is undefined. The purpose of this study was to determine the incidence of sociodemographic data being reported in contemporary foot and ankle RCTs. Methods Randomized-controlled trials within the PubMed database from 2016 to 2021 were searched and the full text of 40 articles was reviewed to identify sociodemographic variables reported in the manuscript. Data regarding race, ethnicity, insurance status, income, work status, and education were collected. Results Race was reported in the results in 4 studies (10.0%), ethnicity in 1 (2.5%), insurance status in 0 (0%), income in 1 (2.5%), work status in 3 (7.5%) and education in 2 (5.0%). In any section other than the results, race was reported in 6 studies (15.0%), ethnicity in 1 (2.5%), insurance status in 3 (7.5%), income in 6 (15.0%), work status in 6 (15.0%), and education in 3 (7.5%). There was no difference in sociodemographic data by journal (P = .212), year of publication (P = .216), or outcome study (P = .604). Conclusion The overall rate of sociodemographic data reported in foot and ankle RCTs is low. There was no difference in the reporting of sociodemographic data between journal, year of publication, or outcome study. Level of Evidence: Level II

Background Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. Methods In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. Results EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. Conclusion This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.