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Engineered neural tissues provide a promising avenue to improve peripheral nerve repair strategies, potentially allowing the precise seeding of cells and materials that support regenerative processes. Current optimization of cell-seeding strategies relies on testing the impact of relevant parameters in vivo, requiring considerable time and resources. We propose an alternative approach to the design of cellular hydrogels based on a mathematical cell\u2013solute model, informed via in vitro experiment, to identify promising cell-seeding strategies in silico at a limited cost. These designs are manufactured using 3D-printed moulds and validated in vivo. We evaluate the regenerative potential of these designs by focusing on the impact of different cell-seeding strategies on vascular endothelial growth factor secretion and gradient generation, both crucial elements of regenerative angiogenesis in early nerve repair. In this way, we provide a first proof-of-concept of a digital twin for nerve tissue engineering, which uses in silico, in vitro and in vivo repair models.<\/jats:p>","DOI":"10.1098\/rsif.2025.0879","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:20:21Z","timestamp":1782260421000},"source":"Crossref","is-referenced-by-count":0,"title":["Bridging the gap: towards a digital twin to optimize therapeutic cell-seeding strategies in nerve tissue engineering"],"prefix":"10.1098","volume":"23","author":[{"given":"Owein","family":"Guillemot-Legris","sequence":"first","affiliation":[{"name":"Centre for Nerve Engineering, University College London 1 , London, UK"},{"name":"Department of Pharmacology, University College London 2 , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1403-1978","authenticated-orcid":false,"given":"Maxime","family":"Berg","sequence":"additional","affiliation":[{"name":"Centre for Nerve Engineering, University College London 1 , London, UK"},{"name":"Department of Mechanical Engineering, University College London 3 , London, UK"},{"name":"Institut de Pharmacologie et Biologie Structurale\u00a0(IPBS), Universit\u00e9 de Toulouse, CNRS 4 , Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-5400","authenticated-orcid":false,"given":"Poppy\u00a0O.","family":"Smith","sequence":"additional","affiliation":[{"name":"Centre for Nerve Engineering, University College London 1 , London, UK"},{"name":"Department of Pharmacology, University College London 2 , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8117-3074","authenticated-orcid":false,"given":"James\u00a0B.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Centre for Nerve Engineering, University College London 1 , London, UK"},{"name":"Department of Pharmacology, University College London 2 , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-6228","authenticated-orcid":false,"given":"Rebecca\u00a0J.","family":"Shipley","sequence":"additional","affiliation":[{"name":"Centre for Nerve Engineering, University College London 1 , London, UK"},{"name":"Department of Mechanical Engineering, University College London 3 , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"2026082409513908200_RSIF20250879C1","doi-asserted-by":"crossref","first-page":"dev201164","DOI":"10.1242\/dev.201164","article-title":"The peripheral nervous system","volume":"150","author":"Murtazina","year":"2023","journal-title":"Development"},{"key":"2026082409513908200_RSIF20250879C2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.bjps.2023.02.017","article-title":"The incidence and management of peripheral nerve injury in England (2005\u20132020)","volume":"80","author":"Murphy","year":"2023","journal-title":"J. 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