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Current therapies address hormonal imbalance but not underlying tissue damage. Strategies involving macrophage modulation and oxidative stress reduction represent a promising target for restoring homeostasis in the irradiated thyroid. Electrospun polycaprolactone (PCL) scaffolds incorporating 0.5%\u20133% adenosine are developed to provide localized modulation of oxidative and inflammatory responses. Adenosine incorporation does not alter scaffold morphology or stability. In vitro studies demonstrate that 1% adenosine scaffolds enhance thyrocyte proliferation, epithelial cohesion, and expression of antioxidant enzymes glutathione peroxidase (\n                    <jats:italic>GPX1<\/jats:italic>\n                    ) and catalase (\n                    <jats:italic>CAT<\/jats:italic>\n                    ), while reducing markers of senescence and apoptosis (\n                    <jats:italic>RGN<\/jats:italic>\n                    ,\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    ,\n                    <jats:italic>CASP3<\/jats:italic>\n                    ). In parallel, adenosine scaffolds regulate THP\u20101\u2010derived macrophage behaviour, promoting a pro\u2010reparative CD206+\/CD163+ phenotype and reducing CD86,\n                    <jats:italic>CD80<\/jats:italic>\n                    , and\n                    <jats:italic>TNF<\/jats:italic>\n                    \u03b1 expression associated with inflammatory activation. This study identifies fibrosis and oxidative stress as contributors to RIHT and demonstrates the feasibility of adenosine\u2010blended scaffolds as a platform for targeting these mechanisms. Macrophage heterogeneity was characterized in the thyroid pre\u2010 and post\u2010irradiation for an immune\u2010guided design. The resulting scaffolds provide a targeted strategy to modulate key contributors to RIHT pathology, laying the groundwork for future in vivo validation.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202501857","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:26:51Z","timestamp":1770186411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Post\u2010Irradiation Thyroid Dysfunction: Electrospun Scaffolds As A Dual\u2010Action Approach for Antioxidant and Immune Modulation"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-4414","authenticated-orcid":false,"given":"Maria","family":"Heim","sequence":"first","affiliation":[{"name":"Institute for Bioengineering, School of Engineering University of Edinburgh Edinburgh UK"},{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3922-627X","authenticated-orcid":false,"given":"Ella\u2010Louise","family":"Handley","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering, School of Engineering University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Grant","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2127-5041","authenticated-orcid":false,"given":"Lizi M.","family":"Hegarty","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair University of Edinburgh Edinburgh UK"},{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-3368","authenticated-orcid":false,"given":"Elaine","family":"Emmerson","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-2853","authenticated-orcid":false,"given":"Anthony","family":"Callanan","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering, School of Engineering University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.48587"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10235503"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab048.1698"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.997288"},{"key":"e_1_2_9_6_1","unstructured":"\u201cCancer Survival Statistics for All Cancers Combined | Cancer Research UK.\u201d [Online]. 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