Bioprinting of a functional vascularized mouse thyroid gland construct

Area of Science:

• Regenerative Medicine
• Bioprinting
• Tissue Engineering

Background:

• Bioprinting utilizes self-assembling tissue spheroids for fabricating 3D tissue and organ constructs.
• The thyroid gland, an endocrine organ, is a suitable model for testing bioprinting technologies.
• Existing bioprinting methods require further advancements for creating functional vascularized organs.

Purpose of the Study:

• To report the bioprinting of a functional, vascularized mouse thyroid gland construct using embryonic tissue spheroids.
• To demonstrate the self-assembly principle for generating thyroid tissue with integrated vascularization.
• To validate the functionality of the bioprinted thyroid construct through in vivo grafting.

Main Methods:

• Generated thyroid spheroids (TS) and allantoic spheroids (AS) as sources of thyrocytes and endothelial cells (EC), respectively.
• Utilized a 3D bioprinter to arrange TS and AS within a collagen hydrogel, guided by mathematical modeling of spheroid fusion.
• Cultured the bioprinted constructs, assessing spheroid fusion, EC invasion, follicle formation, and vascularization.

Main Results:

• Closely printed spheroids fused into a single construct, with AS-derived EC invading and vascularizing TS.
• Thyroid spheroids progressively formed follicles, and a capillary network developed around them, mimicking in utero development.
• Bioprinted constructs normalized thyroxine levels and body temperature when grafted into hypothyroid mice, confirming functionality.

Conclusions:

• Bioprinting using self-assembling tissue spheroids is a viable strategy for creating functional, vascularized thyroid gland constructs.
• This proof-of-concept study advances bioprinting technology by leveraging spheroid self-assembly properties for organ fabrication.
• The developed bioprinting method holds promise for future applications in regenerative medicine and organ transplantation.