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Subretinal implantation of human retinal progenitor cells (hRPCs) has shown great promise in models of retinal degeneration for restoration of vision but is limited by extremely low (&lt; 2%) integration into the retina. Successful integration of implanted cells requires their migration from the site of implantation into the degenerating retina. Little is known about what cues promote RPC migration in the context of the postimplantation microenvironment, such as cues presented by a biomaterial carrier. We utilized a high\u2010throughput assay to study the migration of hRPCs in three\u2010dimensional hydrogel matrices of varying chemical composition and stiffness and, with exposure to different soluble factors, to identify cues important for hRPC migration and associated cell signaling events driving migration. Collagen type I, collagen type I methacrylate, and hyaluronic acid glycidyl methacrylate gels were developed with variable stiffness. The impact of key growth factors in neural development, regeneration, and cell migration such as epidermal growth factor (EGF), fibroblast growth factor (FGF), stromal cell\u2013derived factor (SDF), and hepatocyte growth factor (HGF) was studied using hRPCs in 2\u2009mg\/mL collagen type I gels. Migration of the hRPCs varied significantly in gels of different composition and stiffness, with higher levels of mean migration distance after 48\u2009h in nonphoto crosslinked collagen\u2010based gels with higher concentrations of gel components and associated compressive moduli. In addition, the presence of SDF and HGF in collagen gels increased hRPC migration compared to media alone. Key signaling nodes correlating with hRPC migration were identified in Akt and MAPK signaltransduction pathways using bead\u2010based multiplex ELISA and partial least\u2010squares regression (PLSR) modeling. These results motivate the further exploration of material stiffness and co\u2010delivery of soluble factors as important design parameters in cell delivery vehicles to promote transplanted hRPC migration and successful integration into degenerating retina.<\/jats:p>","DOI":"10.1155\/term\/9963972","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:58:24Z","timestamp":1761703104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human Retinal Progenitor Cell (hRPC) Migration in Three\u2010Dimensional (3D) Environments of Varying Stiffness and Composition"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2167-525X","authenticated-orcid":false,"given":"Peng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5251-2559","authenticated-orcid":false,"given":"Joydip","family":"Kundu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Blanton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahboobeh","family":"Rezaeeyazdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6988-4260","authenticated-orcid":false,"given":"Madeleine J.","family":"Oudin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7638-8898","authenticated-orcid":false,"given":"Miles A.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-1840","authenticated-orcid":false,"given":"Aaron S.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7704-5608","authenticated-orcid":false,"given":"Sidi A.","family":"Bencherif","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-7058","authenticated-orcid":false,"given":"Petr Y.","family":"Baranov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3002-7098","authenticated-orcid":false,"given":"Rebecca L.","family":"Carrier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_11_1_2","volume-title":"Stiffness and Growth Factor Influence on Retinal Progenitor Cell Migration Northeastern University","author":"Blanton D. 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