{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:28:04Z","timestamp":1786375684989,"version":"build-2736575974"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Surg."],"abstract":"<jats:p>\n                    Peripheral nerve injury (PNI) and spinal cord injury (SCI) impose a major burden of traumatic neurological disability worldwide. Autologous nerve grafting, the current gold standard, achieves meaningful recovery in only 81.6% of repairs (2023 meta-analysis,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091,559), while hollow nerve graft conduits achieve only 62.2% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&amp;lt;\u20090.05), with performance declining sharply beyond 20\u201330\u2005mm gaps. Passive scaffolds cannot counter the inhibitory post-injury microenvironment of reactive gliosis, chondroitin sulfate proteoglycan (CSPG) deposition, oxidative stress, and myelin-associated inhibitors, which actively collapse regenerating axon growth cones. This review traces the conceptual and developmental logic of a family of bioactive hydrogels, \u201cneurogels\u201d, designed as active modulators of the regenerative microenvironment rather than passive bridges. We organize the review around the scientific problem: the biological barriers that passive scaffolds cannot address; the design rationale for a hyaluronic acid (HA)-based neurogel bearing a biomimetic laminin-derived peptide (LDP-916), an antioxidant, and an antigliotic immunomodulator; the formulation evolution from the original Guiding Regenerative Gel (GRG; HA\u2009+\u2009LDP-916\u2009+\u2009recombinant superoxide dismutase 1, SOD1) to the current Antigliotic Guiding Regenerative Gel (AGRG; HA\u2009+\u2009LDP-916\u2009+\u2009DL-\u03b1-tocopherol\u2009+\u2009glatiramer acetate); and the preclinical evidence base. An\n                    <jats:italic>in vitro<\/jats:italic>\n                    <jats:sup>35<\/jats:sup>\n                    S-glycosaminoglycan candidate-selection screen in activated astrocytes identified several antigliotic agents; translational barriers of the top-ranked biologics (bacterial origin and thermolability of chondroitinase ABC; blood-brain barrier impermeability of anti-NogoA antibody) motivated selection of glatiramer acetate, the active copolymer of Copaxone (a clinically validated multiple sclerosis drug), and replacement of SOD1 by DL-\u03b1-tocopherol for manufacturing and stability reasons. AGRG increased neurite length by approximately 78%\n                    <jats:italic>in vitro<\/jats:italic>\n                    relative to control, showed electrophysiological performance comparable to or exceeding autograft in a 25\u2005mm chronic rabbit PNI model at 40 weeks, and promoted myelinated axon regrowth in acute and chronic rat SCI. A recently completed 15\u2005mm rat sciatic critical-gap study comparing AGRG to autograft provides supportive internal data; because this dataset has not yet completed independent peer review, its findings are described in general terms and are not used as a basis for definitive efficacy claims. Regulatory-enabling studies are being pursued by Maxonis Ltd. in preparation for an FDA pre-IND interaction.\n                  <\/jats:p>","DOI":"10.3389\/fsurg.2026.1902070","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:33:21Z","timestamp":1786372401000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antigliotic guiding regenerative gel: a bioactive hydrogel platform for peripheral nerve and spinal cord repair"],"prefix":"10.3389","volume":"13","author":[{"given":"Shimon","family":"Rochkind","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Tel-Aviv University","place":["Tel-Aviv, Israel"]},{"name":"Microsurgical Center for Peripheral Nerve Reconstruction, Assuta Medical Center","place":["Tel-Aviv, Israel"]},{"name":"Maxonis Ltd","place":["Ness Ziona, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Almog","sequence":"additional","affiliation":[{"name":"Maxonis Ltd","place":["Ness Ziona, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Goldlust","sequence":"additional","affiliation":[{"name":"Maxonis Ltd","place":["Ness Ziona, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"609638","DOI":"10.3389\/fsurg.2020.609638","article-title":"Reviving matrix for nerve reconstruction in rabbit model of chronic peripheral nerve injury with massive loss defect","volume":"7","author":"Rochkind","year":"2021","journal-title":"Front Surg"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1080\/01616412.2022.2112380","article-title":"Reviving matrix for nerve reconstruction in rat model of acute and 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