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.