3D bioprinting in tissue engineering: current state-of-the-art and challenges towards system standardization and clinical translation.

Journal: Biofabrication
Published Date: Jun 13, 2025

Abstract

Over the past decade, 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 regarding in vitro culturing 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 through 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 like bioprinting in microgravity and the integration of artificial intelligence. The study concludes with the discussions 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. .

Authors

  • Tarun Agarwal
    The George Washington University, Department of Mechanical and Aerospace Engineering, Washington, District of Columbia, 20052-0086, UNITED STATES.
  • Valentina Onesto
    CNR NANOTEC, CNR Nanotec via Monteroni Campus Ecotekne, Lecce, Apulia, 73100, ITALY.
  • Dishary Banerjee
    University of California San Diego, Department of Cardiovascular Research, School of Medicine, La Jolla, California, 92093, UNITED STATES.
  • Shengbo Guo
    The George Washington University, Department of Mechanical and Aerospace Engineering, Washington, District of Columbia, 20052-0086, UNITED STATES.
  • Alessandro Polini
    CNR NANOTEC, CNR NANOTEC, via Monteroni Campus Ecotekne, Lecce, Apulia, 73100, ITALY.
  • Caleb D Vogt
    Medical Scientist Training Program, University of Minnesota Twin Cities, MMC 293 B681 Mayo, 420 Delaware Street SE, Minneapolis, MN 55455, Minneapolis, Minnesota, 55455, UNITED STATES.
  • Abhishek Viswanath
    Institute of Physical Chemistry PAS, Polish Academy of Sciences, Warszawa, 01-224, POLAND.
  • Timothy Esworthy
    Mechanical and aerospace engineering, The George Washington University, 800 22nd Street NW, Washington, District of Columbia, 20052-0086, UNITED STATES.
  • Haitao Cui
    Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing, Sichuan, 400044, CHINA.
  • Aaron O'Donnell
    The Pennsylvania State University, Department of Biomedical Engineering, University Park, 16802-1503, UNITED STATES.
  • Kiran Yellappa Vajanthri
    Chaitanya Bharathi Institute of Technology, Department of Biotechnology, Hyderabad, Telangana, 500075, INDIA.
  • Lorenzo Moroni
    Complex Tissue Regeneration, Maastricht University, Universiteitsingel, 40, Maastricht, 6200 MD, NETHERLANDS.
  • Ibrahim T Ozbolat
    The Pennsylvania State University, Engineering Science and Mechanics Department, University Park, Pennsylvania, 16802-1503, UNITED STATES.
  • Angela Panoskaltsis-Mortari
    Pediatrics, University of Minnesota Medical School Twin Cities, MMC 366, 420 Delaware St. SE, Minneapolis, Minnesota, 55455, UNITED STATES.
  • Lijie Grace Zhang
    The George Washington University, Department of Mechanical and Aerospace Engineering, Washington, District of Columbia, 20052-0086, UNITED STATES.
  • Marco Costantini
    Institute of Physical Chemistry PAS, Polish Academy of Sciences, Warszawa, 01-224, POLAND.
  • Tapas Kumar Maiti
    Indian Institute of Technology Kharagpur, Department of Biotechnology, Kharagpur, 721302, INDIA.

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