Evidence map›Paper›PMID 42526827›Full record

ReviewActa biomaterialia2026

Engineering heterogeneous tissues and organs via multi-material bioprinting: Advances, challenges, and opportunities.

Mohan Wu, Miji Yeo, Irem Deniz Derman, Jiacheng Zhang, Zuoxu Hou, Hongxun Sang, Ibrahim T Ozbolat, Yang Wu

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Acta biomaterialia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Mohan WuSchool of Biomedical Engineering, Harbin Institute of Technology, Shenzhen 518055, China; School of Robotics and Advanced Manufacture, Harbin Institute of Technology, Shenzhen 518055, China.
Miji YeoThe Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA; Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA; Department of Biomedical Science, CHA University, Seongnam 13488, Republic of Korea.
Irem Deniz DermanThe Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA; Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA.
Jiacheng ZhangSchool of Biomedical Engineering, Harbin Institute of Technology, Shenzhen 518055, China; School of Robotics and Advanced Manufacture, Harbin Institute of Technology, Shenzhen 518055, China.
Zuoxu HouDepartment of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
Hongxun SangDepartment of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
Ibrahim T OzbolatThe Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA; Engineering Science and Mechanics Department, Penn State University, University Park, PA 16802, USA; Biotechnology Research and Application Center, Cukurova University, Adana 01130, Turkey; Department of Biomedical Engineering, Penn State University, University Park, PA 16802, USA; Materials Research Institute, Penn State University, University Park, PA 16802, USA; Department of Neurosurgery, Penn State College of Medicine, Hershey 17033, PA, USA; Penn State Cancer Institute, Penn State University, Hershey 17033, PA, USA. Electronic address: ito1@psu.edu.
Yang WuSchool of Biomedical Engineering, Harbin Institute of Technology, Shenzhen 518055, China; School of Robotics and Advanced Manufacture, Harbin Institute of Technology, Shenzhen 518055, China. Electronic address: wuyang2019@hit.edu.cn.

Funding

Leveraging Microsurgery and Bioprinting for Rapidly Oriented Vascularized Tissue EngineeringR01DE035200 · NIDCR · PENNSYLVANIA STATE UNIVERSITY, THE · PI Ibrahim Ozbolat, DINO J RAVNIC · 2025 to 2026
$1.3M
Developing in situ transcriptomics of a bioprinted follicular skin modelR21AR082668 · NIAMS · JACKSON LABORATORY · PI OH, JULIA, OZBOLAT, IBRAHIM · 2023 to 2023
$439k
NIAMS NIH HHS R21 AR082668NIDCR NIH HHS R01 DE035200
6 · The paper itself

Abstract

Native tissues and organs exhibit intrinsic heterogeneity in their structural, compositional, and functional properties, which poses significant challenges towards the development of effective functional substitutes. Multi-material three-dimensional (3D) bioprinting has emerged as a promising strategy to address these challenges by enabling enhanced spatial control over the deposition of biomaterials, signaling factors, and diverse cell types. This capability facilitates the fabrication of heterogeneous tissue constructs that aim to approach the complexity of native tissues, although achieving sub-micron biomimicry remains restricted by current hardware limitations. Recent advances, such as the development of multi-nozzle systems, multi-ink platforms, and the incorporation of heterogeneous cell aggregates, have substantially enhanced the capacity to reproduce tissue heterogeneity with greater precision and scalability. This review provides a comprehensive overview of the fundamental concepts and classifications of multi-material bioprinting. Four representative heterogeneous tissues/organs-osteochondral tissue, trachea, liver, and heart-were selected for in-depth discussion, given their rising clinical significance and escalating bioprinting challenges imposed by their structural and physiological complexity. Furthermore, bioprinting of these tissues/organs covers critical concerns including stiffness, interface connection, biological function, and vascularization. In addition, this Review critically examines the current challenges in the field and offers a forward-looking perspective on emerging trends and potential breakthroughs in technologies in the context of multi-material bioprinting. STATEMENT OF SIGNIFICANCE: This review elaborates on multi-material bioprinting strategies for fabricating heterogeneous tissues and organs. It proposes a classification and definition of heterogeneity at multiple levels, including structural, compositional, and functional aspects, in both native tissues and 3D bioprinting approaches. Moreover, various 3D bioprinting modalities are discussed, encompassing both nozzle-based and nozzle-free techniques, together with their applications in representative heterogeneous organs. This work offers critical insights by addressing current limitations and future opportunities. Together, this review comprehensively categorizes heterogeneous tissue fabrication strategies across diverse multi-material bioprinting approaches, providing a holistic framework for advancing the design and fabrication of next-generation heterogeneous tissues and organs.

Indexed as

Biocompatible MaterialsBioprintingPrinting, Three-DimensionalTissue EngineeringTissue ScaffoldsAnimalsHumansBiocompatible MaterialsBioprintingHeterogeneous tissues/organsMulti-materialScalability

Identifiers

PMID42526827
PMCPMC13596077

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.