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Micromachines
Special Issues
3D Tissue Engineering Techniques and Their Applications
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3D Tissue Engineering Techniques and Their Applications

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B2: Biofabrication and Tissue Engineering".

Deadline for manuscript submissions: closed (31 January 2026) | Viewed by 4141

Special Issue Editor

Dr. Ninghao Zhu

E-Mail Website
Guest Editor
Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS 66506, USA
Interests: tissue engineering; live cell biosensing; organ-on-a-chip; cancer metastasis; drug delivery

Special Issue Information

Dear Colleagues,

We are pleased to launch a Micromachines Special Issue, titled “3D Tissue Engineering Techniques and Their Applications”. This Special Issue aims to highlight emerging scientific and engineering innovations of 3D tissue engineering and their transformative potential in bioscience and biomedical fields.

Recent advances in functional biomaterials, stem cells, and organoid cultures have enabled the development of physiologically relevant tissue-engineered human models in health and diseases. Integrated with novel technologies, such as molecular biosensors and nanomedicines, these tissue-engineered devices offer platforms for real-time molecular monitoring and modeling of live human physiological systems with unprecedented accuracy, resolution, and throughput. These technologies are playing a crucial role in facilitating disease diagnostics, molecular mechanisms, drug delivery, and screening, paving the way for the discovery of innovative therapeutic targets and treatment strategies for human diseases.

We invite interdisciplinary and original research and review articles on diverse topics, including, but not limited to, the following: novel designs of organ-on-chip; organoid culture systems; stem cell culture; biomaterials for 3D scaffolds and drug delivery systems; integrated biosensors; and real-time diagnostic tools and their applications in early disease diagnostics, disease pathway discovery, and drug screening. We specifically encourage contributions regarding human disease modeling and personalized medicines.

By contributing to this Special Issue, you will help create a comprehensive resource for scientists, engineers, and clinicians to combat human diseases with cutting-edge 3D tissue engineering technologies.

We look forward to your contributions.

Dr. Ninghao Zhu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tissue engineering
  • organ-on-chip
  • biosensor
  • biofabrication
  • disease modeling
  • drug delivery
  • drug screening
  • diagnostics
  • biomaterials
  • stem cell culture
  • organoid culture
  • bioMEMS

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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17 pages, 2342 KB  
Article
Integrated Experimental–Computational Framework for Drug Transport Quantification in 3D Microtissues™
by Ramisa Fariha, Jad Hamze, Oluwanifemi David Okoh, Emma Rothkopf and Anubhav Tripathi
Micromachines 2026, 17(3), 332; https://doi.org/10.3390/mi17030332 - 9 Mar 2026
Viewed by 539
Abstract
While traditional 2D in vitro models have been widely used for drug screening, 3D tissue culture systems are gaining traction due to their superior ability to replicate in vivo tumor microenvironments. In this study, we utilize Microtissues™, a validated, scaffold-free, high-throughput 3D [...] Read more.
While traditional 2D in vitro models have been widely used for drug screening, 3D tissue culture systems are gaining traction due to their superior ability to replicate in vivo tumor microenvironments. In this study, we utilize Microtissues™, a validated, scaffold-free, high-throughput 3D tissue culture platform, as the basis for a microscale tissue-engineered model to study drug absorption and transport dynamics. Despite their physiological relevance, such 3D constructs pose analytical challenges, particularly in quantifying trace drug levels within the microenvironment. We developed and validated an integrated experimental workflow combining optimized liquid–liquid extraction and protein precipitation with LC-MS/MS analysis to accurately quantify paclitaxel absorption in Microtissues™ molds using small sample volumes. The assay achieved a validated lower limit of quantification of 0.03 μM, with robust linearity across analytical runs (R2 ≥ 0.90; best-run performance > 0.99) and precision (CV ≤ 10%) across both MRMs. This microengineered in vitro system allows for precise characterization of drug–tissue interactions in MCF7 breast cancer Microtissues™, enabling in vitro-to-in vivo extrapolation (IVIVE) relevant to therapeutic optimization. The platform’s scalability and modularity support its application in precision medicine, where patient-derived microtissues can guide individualized treatment decisions. Full article
(This article belongs to the Special Issue 3D Tissue Engineering Techniques and Their Applications)
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21 pages, 4978 KB  
Article
Hyaluronan-Based Glioblastoma Tumor Constructs Maintain Patient Tumor Drug Responses and Genomic Parity
by Hemamylammal Sivakumar, Steven D. Forsythe, Adrian W. Laxton, Stephen B. Tatter, Lance D. Miller, Roy E. Strowd and Aleksander Skardal
Micromachines 2026, 17(3), 276; https://doi.org/10.3390/mi17030276 - 24 Feb 2026
Viewed by 591
Abstract
Glioblastoma (GBM) is an extremely aggressive and incurable primary tumor of the brain. GBM is characterized by interpatient and intratumoral heterogeneity, making this cancer particularly resistant to therapy and likely to recur. Mapping the complex dynamics that underpin the development and evolution of [...] Read more.
Glioblastoma (GBM) is an extremely aggressive and incurable primary tumor of the brain. GBM is characterized by interpatient and intratumoral heterogeneity, making this cancer particularly resistant to therapy and likely to recur. Mapping the complex dynamics that underpin the development and evolution of gliomas with human-based in vitro models is difficult. This study aimed to generate 3D glioma patient-derived tumor constructs (PTCs) using a clinically relevant, Matrigel-free, hyaluronic acid system, evaluate their suitability in drug screening assays, and determine the stability of their genetic profiles compared to originating tumors. In this study, we utilized a synthetically modified hyaluronic acid and gelatin hydrogel system to generate tumor constructs containing cells from clinical glioma biospecimens. PTCs were characterized phenotypically, after which they were deployed in chemotherapy drug screens using temozolomide (TMZ) and a P53 activator compound. Drug responses of these 3D cultures were compared with 2D cultures, as well as PTCs that were generated after passaging in 2D. RNA sequencing was used to evaluate genetic parity between PTCs or 2D cultures with originating tumor tissues, using The Cancer Genome Atlas (TCGA) GBM subpopulations for subcategorizing. PTCs were created successfully from five World Health Organization (WHO) grade 4, two grade 3, and two grade 2 gliomas. PTCs were maintained with high viability. Chemotherapy drug screens demonstrated that expected TMZ responses were observed for Isocitrate dehydrogenase (IDH) mutant diffuse gliomas while drug response was variable for IDH wildtype GBM PTCs. PTCs demonstrated stable drug response over time, while 2D passaging resulted in significant shifts in drug sensitivity. RNA sequencing revealed maintenance of subpopulation signatures for PTCs which clustered with their originating patient tumor tissue. In contrast, 2D cultures largely clustered together regardless of the patient. Our PTC approach utilizes a defined hydrogel biomaterial system that maintains the genotypic and drug response characteristics of patient tumors making this an ideal ex vivo model for translational applications. Full article
(This article belongs to the Special Issue 3D Tissue Engineering Techniques and Their Applications)
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Review

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20 pages, 4013 KB  
Review
Bioengineering 3D Pancreatic Cancer Models with Fibrotic Stroma for In Vitro Cancer Modeling
by Xingrun Lan, Keke Chen and Xiaoyun Wei
Micromachines 2025, 16(10), 1140; https://doi.org/10.3390/mi16101140 - 2 Oct 2025
Viewed by 2666
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to late diagnosis, high malignancy, and profound resistance to therapy. Traditional two-dimensional (2D) cell cultures fail to recapitulate the complex tumor microenvironment (TME), especially the fibrotic stroma, which is crucial for the progression of PDAC [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to late diagnosis, high malignancy, and profound resistance to therapy. Traditional two-dimensional (2D) cell cultures fail to recapitulate the complex tumor microenvironment (TME), especially the fibrotic stroma, which is crucial for the progression of PDAC and drug response. In vitro three-dimensional (3D) models, which provide more physiologically relevant features such as tight cell–cell and cell-extracellular matrix (ECM) interactions, as well as 3D architecture, have been regarded as highly promising models in PDAC research. This review summarizes some representative in vitro PDAC models, including 3D spheroids, tumor-on-a-chip, bioprinted constructs, and patient-derived organoids (PDOs), particularly focused on the advances in bioengineering strategies for the integration of the key stomal components for microenvironment recapitulation and their applications. Additionally, we discuss the current challenges facing 3D models and propose potential strategies for constructing in vitro models that more accurately simulate the pathophysiology of the fibrotic stroma, aiming for their application in clinical settings. Full article
(This article belongs to the Special Issue 3D Tissue Engineering Techniques and Their Applications)
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