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Here it is aimed to investigate whether tuning the physicochemical properties of implantable biomimetic biomaterial scaffolds can enhance the localized delivery and reparative potential of patient\u2010derived induced pluripotent stem cells (iPSC) astrocyte progenitors. It is demonstrated that soft, collagen\u2010IV\/fibronectin\u2010functionalized hyaluronic acid scaffolds, mimicking the physicochemical properties of healthy spinal cord tissue, optimally support the formation of iPSC\u2010derived multicellular spheroids, promoting neural cell survival and function. These soft, collagen\u2010IV\/fibronectin scaffolds enhance angiogenic cytokine release, facilitate vascular network formation, modulate inflammatory responses, and promote neurite outgrowth from growing, mature and injured neurons, while supporting cell infiltration from spinal cord explants. These findings demonstrate that optimized biomimetic scaffold properties provide a supportive environment for iPSC astrocyte progenitors but can also modulate their reparative capacity. These findings highlight the critical role of matrix composition and scaffold stiffness in advancing scaffold\u2010mediated patient\u2010derived stem cell\u2010delivery strategies for spinal cord repair applications.<\/jats:p>","DOI":"10.1002\/adhm.202500830","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T03:39:22Z","timestamp":1747625962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biomimetic Scaffolds Enhance iPSC Astrocyte Progenitor Angiogenic, Immunomodulatory, and Neurotrophic Capacity in a Stiffness and Matrix\u2010Dependent Manner for Spinal Cord Repair Applications"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9792-2746","authenticated-orcid":false,"given":"Cian","family":"O'Connor","sequence":"first","affiliation":[{"name":"Tissue Engineering Research Group Department of Anatomy &amp; Regenerative Medicine Royal College of Surgeons in Ireland (RCSI)  Dublin 2 Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER) RCSI and Trinity College Dublin (TCD)  Dublin 2 Ireland"},{"name":"Trinity Centre for Biomedical Engineering Trinity College Dublin (TCD)  Dublin 2 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Woods","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group Department of Anatomy &amp; 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