Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, PR China.
Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, PR China.
Acta Biomater. 2020 Jan 1;101:26-42. doi: 10.1016/j.actbio.2019.10.038. Epub 2019 Oct 28.
Four-dimensional (4D) bioprinting, in which the concept of time is integrated with three-dimensional (3D) bioprinting as the fourth dimension, has currently emerged as the next-generation solution of tissue engineering as it presents the possibility of constructing complex, functional structures. 4D bioprinting can be used to fabricate dynamic 3D-patterned biological architectures that will change their shapes under various stimuli by employing stimuli-responsive materials. The functional transformation and maturation of printed cell-laden constructs over time are also regarded as 4D bioprinting, providing unprecedented potential for bone tissue engineering. The shape memory properties of printed structures cater to the need for personalized bone defect repair and the functional maturation procedures promote the osteogenic differentiation of stem cells. In this review, we introduce the application of different stimuli-responsive biomaterials in tissue engineering and a series of 4D bioprinting strategies based on functional transformation of printed structures. Furthermore, we discuss the application of 4D bioprinting in bone tissue engineering, as well as the current challenges and future perspectives. STATEMENTS OF SIGNIFICANCE: In this review, we have demonstrated the 4D bioprinting technologies, which integrate the concept of time within the traditional 3D bioprinting technology as the fourth dimension and facilitate the fabrications of complex, functional biological architectures. These 4D bioprinting structures could go through shape or functional transformation over time via using different stimuli-responsive biomaterials and a series of 4D bioprinting strategies. Moreover, by summarizing potential applications of 4D bioprinting in the field of bone tissue engineering, these emerging technologies could fulfill unaddressed medical requirements. The further discussions about future challenges and perspectives will give us more inspirations about widespread applications of this emerging technology for tissue engineering in biomedical field.
四维（4D）生物打印，即将时间概念融入三维（3D）生物打印作为第四维，目前已成为组织工程的下一代解决方案，因为它提供了构建复杂、功能结构的可能性。4D 生物打印可用于制造动态 3D 图案生物结构，通过使用对刺激有响应的材料，这些结构在受到各种刺激时会改变形状。随着时间的推移，打印细胞载体结构的功能转换和成熟也被视为 4D 生物打印，为骨组织工程提供了前所未有的潜力。打印结构的形状记忆特性满足了个性化骨缺损修复的需求，功能成熟程序促进了干细胞的成骨分化。在这篇综述中，我们介绍了不同刺激响应生物材料在组织工程中的应用以及一系列基于打印结构功能转换的 4D 生物打印策略。此外，我们还讨论了 4D 生物打印在骨组织工程中的应用，以及当前的挑战和未来的展望。
在这篇综述中，我们展示了 4D 生物打印技术，该技术将时间概念融入传统的 3D 生物打印技术中作为第四维，并促进了复杂、功能生物结构的制造。通过使用不同的刺激响应生物材料和一系列 4D 生物打印策略，这些 4D 生物打印结构可以随着时间的推移经历形状或功能的转换。此外，通过总结 4D 生物打印在骨组织工程领域的潜在应用，这些新兴技术可以满足未满足的医疗需求。关于未来挑战和前景的进一步讨论将为我们提供更多关于该新兴技术在生物医学领域组织工程中的广泛应用的启示。
