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Abstract Bioprinting is an additive manufacturing technique that combines living cells, biomaterials, and biological molecules to develop biologically functional constructs. Three-dimensional (3D) bioprinting is commonly used as anin vitromodeling system and is a more accurate representation ofin vivoconditions in comparison to two-dimensional cell culture. Although 3D bioprinting has been utilized in various tissue engineering and clinical applications, it only takes into consideration the initial state of the printed scaffold or object. Four-dimensional (4D) bioprinting has emerged in recent years to incorporate the additional dimension of time within the printed 3D scaffolds. During the 4D bioprinting process, an external stimulus is exposed to the printed construct, which ultimately changes its shape or functionality. By studying how the structures and the embedded cells respond to various stimuli, researchers can gain a deeper understanding of the functionality of native tissues. This review paper will focus on the biomaterial breakthroughs in the newly advancing field of 4D bioprinting and their applications in tissue engineering and regeneration. In addition, the use of smart biomaterials and 4D printing mechanisms for tissue engineering applications is discussed to demonstrate potential insights for novel 4D bioprinting applications. To address the current challenges with this technology, we will conclude with future perspectives involving the incorporation of biological scaffolds and self-assembling nanomaterials in bioprinted tissue constructs.
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This content will become publicly available on August 7, 2026
3D bioprinting in tissue engineering: current state-of-the-art and challenges towards system standardization and clinical translation
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.
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- PAR ID:
- 10630314
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Biofabrication
- Volume:
- 17
- Issue:
- 4
- ISSN:
- 1758-5082
- Page Range / eLocation ID:
- 042003
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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