{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:36:16Z","timestamp":1792467376313,"version":"4.5.0"},"reference-count":224,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-\u03b2, and a growth-factor receptor\u2014performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration.<\/jats:p>","DOI":"10.3390\/ijms27010419","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Phase-Specific Evaluation of Sciatic Nerve Regeneration in Preclinical Studies: A Review of Functional Assessment, Emerging Therapies, and Translational Value"],"prefix":"10.3390","volume":"27","author":[{"given":"Denisa M\u0103d\u0103lina","family":"Viezuin\u0103","sequence":"first","affiliation":[{"name":"U.M.F. Doctoral School Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina (Mu\u0219a)","family":"Burlacu","sequence":"additional","affiliation":[{"name":"U.M.F. Doctoral School Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Gre\u0219i\u021b\u0103","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania"},{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-4791","authenticated-orcid":false,"given":"Irina-Mihaela","family":"Matache","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena-Anca","family":"T\u00e2rtea","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u0103d\u0103lina Iuliana","family":"Mu\u0219at","sequence":"additional","affiliation":[{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Department of Scientific Research Methodology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel-Ovidiu","family":"Amzoiu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8722","authenticated-orcid":false,"given":"Bogdan","family":"C\u0103t\u0103lin","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania"},{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Sfredel","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smaranda Ioana","family":"Mitran","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania"},{"name":"Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12048","DOI":"10.1002\/bmm2.12048","article-title":"Neuromodulation of the Peripheral Nervous System: Bioelectronic Technology and Prospective Developments","volume":"2","author":"Song","year":"2024","journal-title":"BMEMat"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev-cellbio-120320-032429","article-title":"Neurobiology, Stem Cell Biology, and Immunology: An Emerging Triad for Understanding Tissue Homeostasis and Repair","volume":"38","author":"Hsu","year":"2022","journal-title":"Annu. 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