{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:12:24Z","timestamp":1788300744332,"version":"build-2803163510"},"posted":{"date-parts":[[2026,6,4]]},"group-title":"Bioengineering","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21-EB032112"],"award-info":[{"award-number":["R21-EB032112"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wu Tsai Human Performance Alliance"},{"name":"Joe and Clara Tsai Foundation"},{"id":[{"id":"https:\/\/ror.org\/03ht4bd53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Injury to the central nervous system (CNS) causes inflammation, cell death, and glial scar formation that inhibits tissue repair. Injectable hydrogels modified with extracellular matrix (ECM)-derived peptides can provide biochemical cues to promote neural tissue repair and serve as a vehicle to deliver therapeutics across the blood-spinal\/blood-brain barrier in a minimally invasive manner. We developed an injectable hydrazone crosslinked hyaluronic acid-alginate (HA-Alg) hydrogel for neural tissue repair. We fabricated hydrogels with a range of polymer concentrations and evaluated their physicochemical properties to identify formulations that mimic the stiffness and viscoelastic properties of the CNS tissue environment. Hyaluronic acid was further modified with ECM-derived, cell-adhesive peptides (RGD and IKVAV) to enhance neuronal adhesion and viability. To evaluate the therapeutic potential of our hydrogel platform, we embedded mouse embryonic stem cell aggregates and differentiated them toward mature V2a interneurons. These interneurons are critical for relaying motor signals and represent a promising therapeutic cell population for treating spinal cord injuries. We demonstrated successful enrichment for V2a interneurons in HA-Alg hydrogels containing ECM-derived peptides. Interestingly, both our newly described HA-Alg and established crosslinked HA-HA hydrogels containing IKVAV peptides demonstrated significantly increased neurite length in interneuron enriched cultures compared to hydrogels without peptides. This study demonstrates that the addition of ECM-derived peptides is essential to support the neuronal adhesion and viability required for functional CNS tissue repair.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"729352v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Statement of Significance<\/jats:title>\n                  <jats:p>Development of injectable, peptide-modified hyaluronic acid alginate hydrogels to support neuronal maturation for central nervous system tissue repair.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.01.729352","type":"posted-content","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:10:13Z","timestamp":1780611013000},"source":"Crossref","is-referenced-by-count":1,"title":["Hyaluronic Acid-Alginate Hydrazone Crosslinked Hydrogels Support the Generation and Maturation of V2a Interneurons"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3398-0506","authenticated-orcid":false,"given":"Alycia N.","family":"Galindo","sequence":"first","affiliation":[{"name":"Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison E.","family":"McLaren","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Rice University, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa K.","family":"Chi","sequence":"additional","affiliation":[{"name":"Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR"},{"name":"Department of Bioengineering, Rice University, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9972-6540","authenticated-orcid":false,"given":"Jenna D.","family":"Khachatourian","sequence":"additional","affiliation":[{"name":"Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR"},{"name":"Department of Human Physiology, University of Oregon, Eugene, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Butts","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Rice University, Houston, TX"},{"name":"Neuroengineering Initiative, Rice University, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-4575","authenticated-orcid":false,"given":"Marian H.","family":"Hettiaratchi","sequence":"additional","affiliation":[{"name":"Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR"},{"name":"Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR"},{"name":"Institute of Molecular Biology, University of Oregon, Eugene, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060801001811000_2026.06.01.729352v1.1","unstructured":"Thau, L. ; Reddy, V. ; Singh, P. 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