{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:01:17Z","timestamp":1790618477628,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advanced Biology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Silk hydrogels have attracted increasing interest as biocompatible substrates for neural cell culture and regenerative research. Recent research has shown that activation of exchange protein directly activated by cAMP 2 (Epac2) promotes neurite outgrowth in several neuronal models. Here, we investigated the effects of\n                    <jats:italic>Bombyx mori<\/jats:italic>\n                    silk hydrogel, alone or in combination with S\u2010220, a non\u2010hydrolysable cAMP analogue that selectively activates Epac2, on neurite outgrowth. Epac2 activation significantly and dose\u2010dependently enhanced both the total and longest neurite length. Neurons cultured on silk hydrogel alone exhibited neurite outgrowth comparable to control neurons, indicating good biocompatibility of the hydrogel. Addition of S\u2010220 to the culture medium with silk hydrogel modestly improved neurite morphology; however, incorporation of S\u2010220 directly into the hydrogel did not enhance neurite outgrowth but instead reduced neurite length. A subsequently established three\u2010dimensional cortical neuron culture model using silk hydrogel supported neurite extension and increased branching complexity beyond that observed with two\u2010dimensional cultures, despite a shorter overall neurite length. Collectively, these findings support silk hydrogel as a permissive biomaterial substrate for in vitro cortical neuron culture. The system provides a useful platform for investigating neurite outgrowth, neuron\u2010biomaterial interactions and the delivery of bioactive compounds in two\u2010 and three\u2010dimensional neural cultures.\n                  <\/jats:p>","DOI":"10.1002\/adbi.70157","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:07:21Z","timestamp":1788872841000},"source":"Crossref","is-referenced-by-count":0,"title":["The Impact of S\u2010220\u2013Loaded Silk Hydrogels on In Vitro Neurite Outgrowth in 2 and 3 Dimensions"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-000X","authenticated-orcid":false,"given":"Hongming","family":"Ma","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences School of Medicine Medical Sciences &amp; Nutrition University of Aberdeen Aberdeen Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1955-1975","authenticated-orcid":false,"given":"F. Philipp","family":"Seib","sequence":"additional","affiliation":[{"name":"Pharmaceutical Technology &amp; Biopharmaceutics Institute of Pharmacy Friedrich Schiller University Jena  Jena Germany"},{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde Glasgow Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3611-5654","authenticated-orcid":false,"given":"Wenlong","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences School of Medicine Medical Sciences &amp; Nutrition University of Aberdeen Aberdeen Scotland 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