Phase-Specific Evaluation of Sciatic Nerve Regeneration in Preclinical Studies - A Review of Functional Assessment, Emerging Therapies, and Translational Value

Sep 30, 2026

Peripheral nerve injuries, especially those affecting the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and limited translation of preclinical advances into effective therapies. This review consolidates evidence on phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. Functional readouts are mapped to underlying biological events, highlighting complementary assessment tools such as the Sciatic Functional Index, Beam Walk, Rotarod, nerve conduction studies, and nociceptive assays. Emerging interventions are analyzed with emphasis on matching mechanisms to the dynamic repair microenvironment, while publication trend analysis underscores a persistent translational gap. A targeted computational analysis of alpha-lipoic acid is also presented to illustrate molecular-level characterization that complements mechanistic insights.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Abstract

Introduction

Peripheral nervous system overview and injury impact

Mechanisms and consequences of peripheral nerve injuries

Historical classification framework (Seddon) and lesion types

Review Phase-Specific Evaluation of Sciatic Nerve Regeneration in Preclinical Studies: A Review of Functional Assessment, Emerging Therapies, and Translational Value Denisa Mădălina Viezuină 1,†, Irina (Mus, a) Burlacu 1,†, Andrei Gres, iă 2,3,*, Irina-Mihaela Matache 4, *, Elena-Anca Târtea 5, Mădălina Iuliana Mus, at 3,6, Manuel-Ovidiu Amzoiu 7, Bogdan Cătălin 2,3, Veronica Sfredel 2 and Smaranda Ioana Mitran 2,3 Academic Editor: KiminobuSugaya Received: 12 December 2025 Revised: 27 December 2025 Accepted: 28 December 2025 Published: 31 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 U.M.F. Doctoral School Craiova, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; [irinamusa23@yahoo.com](irinamusa23@yahoo.com) (I.B.) 2 Department of Physiology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania; [bogdan.catalin@umfcv.ro](bogdan.catalin@umfcv.ro) (B.C.); veronica.sfredel@umfcv.ro (V.S.); [smaranda.mitran@umfcv.ro](smaranda.mitran@umfcv.ro) (S.I.M.) 3 Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; [madalina.musat@umfcv.ro](madalina.musat@umfcv.ro) 4 Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania 5 Department of Neurology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; [anca.tartea@umfcv.ro](anca.tartea@umfcv.ro) 6 Department of Scientific Research Methodology, University of Medicine and Pharmacy of Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania 7 Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania; [manuel.amzoiu@umfcv.ro](manuel.amzoiu@umfcv.ro) * Correspondence: [andrei.gresita@umfcv.ro](andrei.gresita@umfcv.ro) (A.G.); [irina.m.matache@gmail.com](irina.m.matache@gmail.com) (I.-M.M.)† These authors contributed equally to this work. Abstract 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 advancementsin 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-β, and a growth-factor receptor—performed

FAQs

Why is phase-specific evaluation important for sciatic nerve regeneration studies?

Different phases of regeneration involve distinct biological events, so functional readouts need to be aligned with the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative processes to yield interpretable outcomes.

Which assessment tools are highlighted for evaluating sciatic nerve recovery?

The review emphasizes the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays, noting that they provide complementary information on motor, sensory, and neuromuscular recovery.

What therapeutic strategies are discussed as emerging approaches?

Emerging strategies include intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules.

Sep 30, 2026

Uploaded by eBook King