Restoring thyroid function with tissue-engineered products after total thyroidectomy

Abstract

Introduction: Post-thyroidectomy hypothyroidism is a common complication of total thyroid removal, traditionally managed with lifelong hormone replacement therapy. Thyroid models developed through tissue engineering represent innovative approaches to restore endocrine function. This study summarizes recent advances in thyroid tissue engineering and compares the efficacy and practical potential of various methods. Materials and Methods: We conducted a narrative review using articles published between 2009- 2025, focusing on autologous thyroid transplants, stem cell-derived thyrocytes, organoids, hydrogel scaffolds, and decellularized matrices. Preclinical and in vitro outcomes assessed included thyroid hormone production (T3, T4, TSH), follicular architecture, vascularization, and long-term stability. We synthesized the data descriptively to compare functional restoration and practical feasibility. Results: Autologous thyroid cell sheets transplanted into pre-vascularized, retrievable Cell Pouch™ devices restored serum T3 and T4 to 95-100% of baseline in rat models within 4-7 weeks. Histology attested 95% normal follicular architecture and angiogenesis in all grafts, with endocrine function maintained till 20 weeks. Pluripotent stem cells differentiated into thyroid follicular cells expressed NKX2-1 and PAX8 in >90% of cells. These cells secreted T4 at 80- 85% of what native tissue produces in vitro, but in vivo endocrine rescue reached only 30-40% of normal serum T4. Decellularized human thyroid scaffolds and hydrogel matrices increased cell survival by 70-80%, maintained follicular organization in ~85% of constructs, and encouraged blood vessel growth. Thyroid organoids from fetal and adult tissues proved over 90% efficiency in forming follicles and produced hormones reaching 75-80% of normal T4 output. Comparative analysis indicates that autologous transplantation in vascularized devices currently provides the strongest restoration of thyroid function. Meanwhile, stem cell and organoid-based strategies have significant potential for personalized regenerative therapies. Conclusions: Tissue-engineered methods can restore post-thyroidectomy endocrine function, with autologous thyroid cell transplantation in pre-vascularized devices demonstrating good efficiency in preclinical studies. Stem cell-derived thyrocytes, organoids, and hydrogel scaffolds give complementary platforms for functional restoration and future clinical applications. Further exploration is necessary to optimize scalability, vascularization, immune compatibility, and long- term safety for human implementation.