Advances in Thyroid Gland Regeneration: The Integrated Approach of Cell Biology and Bioengineering

Abstract

The thyroid gland is an endocrine organ responsible for production of triiodothyronine and thyroxine, essential hormones that regulate human metabolism. A wide range of conditions can impair its function, leading to potential life-threatening consequences such as myxedema coma. The standard treatment for hypothyroidism is lifelong levothyroxine supplementation, which, despite being a significant therapeutic breakthrough, has notable limitations and does not fully restore quality of life for many patients. Biomimetic thyroid gland has emerged as a promising alternative treatment strategy for patients with hypothyroidism. Most research to date has focused on generating thyroid organoids from primary thyroid cells or stem cells. However, there is growing interest in other approaches, including the use of biomaterials, bioreactors, and 3D bioprinting as potential alternatives or supplementary technologies to the organoids. While in vitro and preclinical studies have shown encouraging results, clinical application of biomimetic thyroid gland requires further studies in several key areas, including long-term functional validation, studies on large animal models, immunological compatibility and scaffold biodegradation, and absence of standardized good manufacturing practice (GMP)-compliant production protocols.

Impact Statement

Endocrine gland regeneration remains a significant challenge in tissue engineering due to their morphological and physiological complexity. Although hormonal replacement therapy with levothyroxine has been a major breakthrough in managing hypothyroidism, there is still a pressing need for developing a biomimetic thyroid gland. This comprehensive review examines the rapidly advancing area of thyroid gland regeneration, highlighting the most recent and most impactful developments in both cell biology and bioengineering disciplines. By emphasizing the complementary roles of cellular and bioengineering approaches to thyroid regeneration, the review offers an encouraging outlook for the development potential of functional, physiologically regulated biomimetic thyroid gland.