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Abstract Over the past decade, three-dimensional (3D) bioprinting has made significant progress, transforming into a key innovation in tissue engineering. Despite the early strides, critical challenges remain in 3D bioprinting that must be addressed to accelerate clinical translation. In particular, there is still a long way to go before functionally-mature, clinically-relevant tissue equivalents are developed. Current limitations range from the sub-optimal bioink properties and degree of biomimicry of bioprintable architectures, to the lack of stem/progenitor cells for massive cell expansion, and fundamental knowledge regardingin vitroculturing conditions. In addition to these problems, the absence of guidelines and well-regulated international standards is creating uncertainty among the biofabrication community stakeholders regarding the reliable and scalable production processes. This review aims at exploring the latest developments in 3D bioprinting approaches, including various additive manufacturing techniques and their applications. A thorough discussion of common bioprinting techniques and recent progresses are compiled along with notable recent studies. Later we discuss the current challenges in clinical application of 3D bioprinting and the major bottlenecks in the commercialization of 3D bioprinted tissue equivalents, including the longevity of bioprinted organs, meeting biomechanical requirements, and the often underrated ethical and legal aspects. Amidst the progress of regulatory efforts for regenerative medicine, we also present an overview of the current regulatory concerns which should be taken into account to translate bioprinted tissues into clinical practice. At last, this review emphasizes future directions in 3D bioprinting that includes the transformative ideas such as bioprinting in microgravity and the integration of artificial intelligence. The study concludes with a discussion on the need for collaborative efforts in resolving the technical and regulatory constraints to improve the quality, reliability, and reproducibility of bioprinted tissue equivalents to ultimately accomplish their successful clinical implementation.more » « lessFree, publicly-accessible full text available August 7, 2026
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Three‐dimensional (3D) printing is an emerging technique that has shown promising success in engineering human tissues in recent years. Further development of vat‐photopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components. Similarly, the development of microfluidic chip systems is an emerging research sector with promising medical applications. This work demonstrates the coupling of a digital light processing (DLP) printing procedure with a microfluidic chip system to produce size‐tunable, 3D‐printable porosities with narrow pore size distributions within a gelatin methacryloyl (GelMA) hydrogel matrix. It is found that the generation of size‐tunable gas bubbles trapped within an aqueous GelMA hydrogel‐precursor can be controlled with high precision. Furthermore, the porosities are printed in two‐dimensional (2D) as well as in 3D using the DLP printer. In addition, the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts, where high cell viabilities as well as cell proliferation, spreading, and migration are confirmed. It is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine, among others.more » « less
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Nature's material systems during evolution have developed the ability to respond and adapt to environmental stimuli through the generation of complex structures capable of varying their functions across direction, distances and time. 3D printing technologies can recapitulate structural motifs present in natural materials, and efforts are currently being made on the technological side to improve printing resolution, shape fidelity, and printing speed. However, an intrinsic limitation of this technology is that printed objects are static and thus inadequate to dynamically reshape when subjected to external stimuli. In recent years, this issue has been addressed with the design and precise deployment of smart materials that can undergo a programmed morphing in response to a stimulus. The term 4D printing was coined to indicate the combined use of additive manufacturing, smart materials, and careful design of appropriate geometries. In this review, we report the recent progress in the design and development of smart materials that are actuated by different stimuli and their exploitation within additive manufacturing to produce biomimetic structures with important repercussions in different but interrelated biomedical areas.more » « less
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