Estrogen-loaded scaffolds promote thyrocyte proliferation and endogenous antioxidant expression while preserving functional stability

Loss of functional thyrocytes following thyroid injury or radiotherapy remains a significant clinical challenge, motivating development of biomaterial-based strategies to support thyroid cell survival and function. 17beta-Estradiol (E2) has been shown to promote thyrocyte proliferation and antioxidant responses, although systemic or bolus delivery may induce cytotoxicity and raises concerns regarding long-term pathological effects. Here, electrospun polycaprolactone (PCL) scaffolds incorporating varying concentrations of E2 were developed as a localized hormone delivery platform for thyroid epithelial cells.

E2 incorporation altered scaffold mechanical behaviour, hydrophilicity, and porosity in a concentration-dependent manner while preserving fibre morphology, crystallinity, and thermal stability. Scaffold- mediated E2 delivery supported sustained thyrocyte viability and proliferation compared with bolus E2 exposure, with intermediate E2 concentrations producing the most favourable biological response. Morphological analysis demonstrated extensive cell spreading and organised cytoskeletal structures without features associated with apoptosis. Although E2-loaded scaffolds did not exhibit direct radical scavenging activity, they promoted upregulation of antioxidant-associated genes, indicating indirect modulation of cellular redox homeostasis.

Thyroid-specific functional markers associated with hormone synthesis and maintenance of the differentiated thyroid phenotype were largely preserved across scaffold groups during the 14-day culture period. Furthermore, no detectable \textit{BRAF} V600E or V600K mutations were identified under any condition tested. Collectively, these findings demonstrate that electrospun E2@PCL scaffolds provide a tunable microenvironment capable of supporting thyrocyte survival, proliferation, and functional maintenance, highlighting their potential for thyroid tissue engineering applications targeting radiation-induced thyroid injury.