Zhang Daiyao, Huerta-López Carla, Heilshorn Sarah C
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
Curr Opin Biomed Eng. 2025 Sep;35. doi: 10.1016/j.cobme.2025.100607. Epub 2025 Jun 5.
The development of organoid cultures has propelled the fields of cell biology, tissue engineering, and regenerative medicine forward. These cultures better mimic tissue structure and function compared to 2D cell culture; however, organoids are limited in size and do not inherently allow precise control over tissue architecture and cell heterogeneity. Hand-wrought organoid biofabrication approaches enable the production of larger and more complex tissues, but they still lack reproducible control of spatiotemporal tissue patterns. In contrast, bioprinting is a collection of machine-wrought technologies that are emerging as powerful tools in tissue engineering and disease modeling, but have not yet been widely applied to organoids. When combined with advances in biomaterials science, bioprinting offers the possibility to control spatiotemporal cellular and microenvironmental features. The interactions between biomaterial inks, support baths, and embedded cells provide the opportunity to guide the maturation and functionality of engineered tissues. This review describes how recent advances in organoid technology, bioprinting, and biomaterials science can be integrated to achieve spatiotemporal patterning of four aspects of the microenvironment: matrix structure and mechanics, matrix ligands and morphogens, co-culture of multiple cell types, and incorporation of vasculature. These insights underscore the potential for organoid bioprinting to advance the fabrication of tissue mimics for applications in drug screening, disease modeling, and regenerative medicine.
类器官培养技术的发展推动了细胞生物学、组织工程和再生医学领域的进步。与二维细胞培养相比，这些培养物能更好地模拟组织结构和功能；然而，类器官在尺寸上存在限制，并且无法内在地实现对组织结构和细胞异质性的精确控制。手工制作类器官的生物制造方法能够生产更大、更复杂的组织，但它们仍然缺乏对时空组织模式的可重复控制。相比之下，生物打印是一系列机器制造技术，正在成为组织工程和疾病建模中的强大工具，但尚未广泛应用于类器官。当与生物材料科学的进展相结合时，生物打印提供了控制时空细胞和微环境特征的可能性。生物材料墨水、支撑浴和嵌入细胞之间的相互作用为引导工程组织的成熟和功能提供了机会。本综述描述了如何将类器官技术、生物打印和生物材料科学的最新进展整合起来，以实现微环境四个方面的时空模式化：基质结构和力学、基质配体和形态发生素、多种细胞类型的共培养以及血管系统的整合。这些见解强调了类器官生物打印在推进用于药物筛选、疾病建模和再生医学的组织模拟物制造方面的潜力。
