{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:06:10Z","timestamp":1787504770674,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of South Africa","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"NRF South African Research Chairs Initiative","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"University Research Committee of the University of the Witwatersrand","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Optimal levels of functional recovery in peripheral nerve injuries remain elusive due to the architectural complexity of the neuronal environment. Commercial nerve repair conduits lack essential guidance cues for the regenerating axons. In this study, the regenerative potential of a biosimulated nerve repair system providing three types of regenerative cues was evaluated in a 10 mm sciatic nerve-gap model over 4 weeks. A thermo-ionically crosslinked gellan-xanthan hydrogel conduit loaded with electrospun PHBV-magnesium oleate-N-acetyl-cysteine (PHBV-MgOl-NAC) nanofibers was assessed for mechanical properties, nerve growth factor (NGF) release kinetics and PC12 viability. In vivo functional recovery was based on walking track analysis, gastrocnemius muscle mass and histological analysis. As an intraluminal filler, PHBV-MgOl-NAC nanofibers improved matrix resilience, deformation and fracture of the hydrogel conduit. NGF release was sustained over 4 weeks, governed by Fickian diffusion and Case-II relaxational release for the hollow conduit and the nanofiber-loaded conduit, respectively. The intraluminal fibers supported PC12 proliferation by 49% compared to the control, preserved up to 43% muscle mass and gradually improved functional recovery. The combined elements of physical guidance (nanofibrous scaffolding), chemical cues (N-acetyl-cysteine and magnesium oleate) and therapeutic cues (NGF and diclofenac sodium) offers a promising strategy for the regeneration of severed peripheral nerves.<\/jats:p>","DOI":"10.3390\/ijms222111555","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"11555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Gellan-Xanthan Hydrogel Conduits with Intraluminal Electrospun Nanofibers as Physical, Chemical and Therapeutic Cues for Peripheral Nerve Repair"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-155X","authenticated-orcid":false,"given":"Poornima","family":"Ramburrun","sequence":"first","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-4350","authenticated-orcid":false,"given":"Pradeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Ndobe","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-1529","authenticated-orcid":false,"given":"Yahya E.","family":"Choonara","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8402","DOI":"10.1016\/j.biomaterials.2010.07.052","article-title":"Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats","volume":"31","author":"Madduri","year":"2010","journal-title":"Biomaterials"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1179\/016164104225013798","article-title":"Peripheral nerve regeneration through guidance tubes","volume":"26","author":"Belkas","year":"2013","journal-title":"Neurol. 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