{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:44:22Z","timestamp":1787802262461,"version":"build-2784847793"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine","award":["W81XWH-15-1-0026"],"award-info":[{"award-number":["W81XWH-15-1-0026"]}]},{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine","award":["W81XWH-14-1-0421"],"award-info":[{"award-number":["W81XWH-14-1-0421"]}]},{"name":"Department of Defense Office of Congressionally Directed Medical Research Program","award":["W81XWH-15-1-0026"],"award-info":[{"award-number":["W81XWH-15-1-0026"]}]},{"name":"Department of Defense Office of Congressionally Directed Medical Research Program","award":["W81XWH-14-1-0421"],"award-info":[{"award-number":["W81XWH-14-1-0421"]}]},{"name":"Department of Defense (U.S. Army Medical Research and Materiel Command)","award":["W81XWH-15-1-0026"],"award-info":[{"award-number":["W81XWH-15-1-0026"]}]},{"name":"Department of Defense (U.S. Army Medical Research and Materiel Command)","award":["W81XWH-14-1-0421"],"award-info":[{"award-number":["W81XWH-14-1-0421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ \u2265 2.0 ng\/mL); whereas the drug concentrations within the ION and muscle were much higher, demonstrating the local delivery of FK506 to treat PNI. An immunohistological assessment of ION showed increased myelin expression for animals assigned to neurorrhaphy with PEUU-FK506 treatment compared to untreated or systemic-FK506-treated animals, suggesting that improved PNI outcomes using PEUU-FK506 is mediated by the modulation of Schwann cell activity.<\/jats:p>","DOI":"10.3390\/ijms25020847","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T07:50:48Z","timestamp":1704873048000},"page":"847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nerve Wrap for Local Delivery of FK506\/Tacrolimus Accelerates Nerve Regeneration"],"prefix":"10.3390","volume":"25","author":[{"given":"Bo","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-4201","authenticated-orcid":false,"given":"Firuz","family":"Feturi","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-6107","authenticated-orcid":false,"given":"An-Jey A.","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"},{"name":"Department of Surgery, Division of Plastic Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolandi","family":"Van der Merwe","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Diego, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayvon","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil J.","family":"Khatter","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan B.","family":"Katzel","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-3290","authenticated-orcid":false,"given":"Raman","family":"Venkataramanan","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario G.","family":"Solari","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Wagner","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-8898","authenticated-orcid":false,"given":"Michael B.","family":"Steketee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Diego, CA 90095, USA"},{"name":"McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Simons","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kia M.","family":"Washington","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Pittsburgh School of Medicine, Veterans Administration Healthcare System, Pittsburgh, PA 15213, USA"},{"name":"Department of Surgery, Division of Plastic Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/PHM.0b013e31815e6370","article-title":"The incidence of peripheral nerve injury in extremity trauma","volume":"87","author":"Taylor","year":"2008","journal-title":"Am. 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