Tissue Engineering
Master’s in Biomedical Engineering
Thyroid Tissue Engineering
Authors:
Group 7
Instituto Superior Técnico
Tissue Engineering
Contents
1. Abstract 1
1.1. Problem Definition 1
1.2. Background and Vision 1
1.3. Motivations 1
1.4. Challenges 2
2. References 2
Instituto Superior Técnico
Tissue Engineering
1. Abstract
1.1. Problem Definition
The thyroid is an endocrine gland responsible for producing thyroid hormones (T3 and T4) and
maintaining iodine balance in the body (Armstrong, Asuka, & Fingeret, 2023). These hormones are
vital for processes like organ development, growth, and energy metabolism (Romitti & Costagliola,
2023). Diseases affecting the thyroid, such as congenital hypothyroidism, cancer, traumas, etc., can
impair hormone synthesis (Weng et al., 2021).
Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, accounting for 80-85% of
cases (Coca-Pelaz et al., 2020).
The primary treatment for PTC is surgery, which may involve partial or total thyroidectomy. If cancer
has spread to lymph nodes, they may also be removed. Additional treatments like radioiodine therapy
or radiation may be used to target remaining cancer cells. A common outcome of these therapies is
permanent hypothyroidism (Cleveland Clinic, 2024 describes papillary thyroid cancer (PTC)). This
condition is characterized by a reduction in the synthesis and secretion of thyroid hormones,
significantly impacting intellectual development and physical growth (Zhang et al., 2024).
1.2. Background and Vision
Tissue engineering emerges as a potential solution to this problem, combining cells and biomaterials
to construct bioengineered thyroid tissue (Zhang et al., 2024).
This study focuses on the development and characterization of a novel injectable 3D hydrogel derived
from the thyroid extracellular matrix (TEM) for thyroid tissue engineering. TEM hydrogels were
prepared through the decellularization of rat thyroid tissue, followed by extensive physicochemical and
mechanical property evaluations. The aim was to assess whether TEM hydrogels exhibit properties
similar to those of natural thyroid tissue, including high biocompatibility and a complex 3D
ultrastructure.
The behavior of thyroid hormone-secreting cells cultured in TEM hydrogels was compared to those
cultured in traditional type I collagen hydrogels, in terms of their viability, hormone secretion, and
gene expression. Finally, the goal was to test whether there would be significant retention of growth
factors and extracellular matrix proteins within the TEM hydrogels.
This research contributes to a new possibility for thyroid tissue engineering, offering a promising
alternative for the treatment of hypothyroidism (Zhang et al., 2024).
1.3. Motivations
Current treatments, including hormone replacement therapy and thyroid transplantation, have
limitations due to issues such as hormone dosage control and immune rejection. Thus it is important to
invest in and explore new therapies with different approaches that can address these problems (Zhang
et al., 2024).
With the advancement of science and the need to explore more efficient therapies, extracellular matrix
(ECM) hydrogels have garnered attention in the field of tissue engineering in recent years (Zhang et al.,
2024). Furthermore, ECM materials are rich in cytokines and growth factors that induce and regulate
cell growth, proliferation, and differentiation, providing a favorable microenvironment for cell
adhesion, proliferation, and differentiation (Keane, Swinehart, & Badylak, 2015).
Another main motivation is that PTC accounts for the majority of thyroid cancer cases, often leading to
hypothyroidism, highlighting an increased need to develop a therapy that addresses this need.
1.4. Challenges
Although tissue engineering techniques, particularly those utilizing biomaterials derived from the
ECM, show great potential for the treatment of hypothyroidism, significant challenges remain to be
addressed. Some issues are preserving ECM functionality, optimizing nutrient diffusion, improving
mechanical properties, and overcoming barriers imposed by the tumor microenvironment are critical
factors. Furthermore, ensuring the scalability, reproducibility, and functional integration of the
developed materials is essential for clinical success (Zhang et al., 2024).
1
Instituto Superior Técnico
Tissue Engineering
2. References
1 . Armstrong, M., Asuka, E., & Fingeret, A. (2023, March 13). Physiology, thyroid function. StatPearls.
2. Coca-Pelaz, A., Shah, J. P., Hernandez-Prera, J. C., Ghossein, R. A., Rodrigo, J. P., Hartl, D. M., Olsen, K. D.,
Shaha, A. R., Zafereo, M., Suarez, C., Nixon, I. J., Randolph, G. W., Mäkitie, A. A., Kowalski, L. P., Poorten, V.
V., Sanabria, A., Guntinas-Lichius, O., Simo, R., Zbären, P., . . . Ferlito, A. (2020). Papillary thyroid
cancer—Aggressive variants and impact on management: A narrative review. Advances in Therapy,
37(7), 3112-3128.
3. Keane, T. J., Swinehart, I. T., & Badylak, S. F. (2015). Methods of tissue decellularization used for
preparation of biologic scaffolds and in vivo relevance. Methods, 84, 25–34.
4. Papillary thyroid cancer (PTC). (2024, October 21). Cleveland Clinic.
5. Romitti, M., & Costagliola, S. (2023). Progress toward and challenges remaining for thyroid tissue
regeneration. Endocrinology, 164(10), Article bqad136.
6. Weng, J., Chen, B., Xie, M., Wan, X., Wang, P., Zhou, X., Zhou, Z., Mei, J., Wang, L., Huang, D., Wang, Z.,
Wang, Z., & Chen, C. (2021). Rabbit thyroid extracellular matrix as a 3D bioscaffold for thyroid
bioengineering: A preliminary in vitro study. BioMedical Engineering OnLine, 20(1), 81.
7. Zhang, L., Long, H., Zhang, P., Liu, B., Li, S., Sun, R., Diao, T., & Li, F. (2024). Development and
characterization of a novel injectable thyroid extracellular matrix hydrogel for enhanced thyroid tissue
engineering applications. Frontiers in Bioengineering and Biotechnology, 12, 1481295.
