Estrogen-Loaded Scaffolds Modulate Thyrocyte Proliferation and Redox Homeostasis Without Oncogenic Risk

Loss of functional thyrocytes following thyroid injury or radiotherapy remains a clinical chal- lenge, motivating the development of biomaterial-based strategies to support thyroid cell survival and regeneration. 17β-Estradiol (E2) has been shown to promote thyrocyte pro- liferation. However, systemic or bolus delivery can induce cytotoxicity and raises concerns regarding oncogenic risk. Here, electrospun polycaprolactone (PCL) scaffolds incorporating concentrations of E2 were developed as a localized hormone delivery platform for thyroid epithelial cells. E2 incorporation altered scaffold mechanical properties in a concentration-dependent man- ner while preserving fibre morphology, crystallinity, and thermal stability. Scaffold-mediated delivery supported sustained thyrocyte viability and proliferation compared with bolus E2 exposure. Intermediate E2 concentrations produced the most favourable biological response. Morphological analysis revealed extensive cell spreading and organised cytoskeletal structures without features indicative of apoptosis. As expected, E2-loaded scaffolds did not exhibit direct radical scavenging activity, but promoted upregulation of endogenous antioxidant en- zymes, indicating indirect modulation of cellular redox homeostasis. Importantly, expression of thyroid-specific functional markers was largely maintained, and no oncogenic BRAF mutations were detected under any condition. These findings demonstrate that controlled E2 delivery via electrospun scaffolds supports thyrocyte proliferation and redox balance while preserving function, highlighting their potential as tissue engineering therapeutics for thyroid radiation injury.