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Bioengineering
Special Issues
Biofabrication of Biologically Realistic Constructs: Needs, Challenges, and Opportunities
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Biofabrication of Biologically Realistic Constructs: Needs, Challenges, and Opportunities

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Nanobiotechnology and Biofabrication".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 3111

Editor

Dr. Nicanor Ilie Moldovan

E-Mail Website
Guest Editor
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Interests: 3D bioprinting; biofabrication; tissue engineering; vascular biomedicine

Special Issue Information

Dear Colleagues,

This Special Issue of Bioengineering, titled "Biofabrication of Biologically Realistic Constructs: Needs, Challenges, and Opportunities", aims to showcase an emerging paradigm shift in tissue engineering from technology-driven developments to biology-driven implementations that prioritize structural and functional fidelity. This Special Issue addresses a current challenge in the field: the disconnect between engineering capabilities and the structure–function paradigm that governs biological systems. We will highlight innovative methods, biomaterials, and technologies—including single-cell manipulation, bioprinting, and advanced imaging—that strive to enable faithful reproduction of biological complexity. Contributors are invited to cover topics such as construct shape fidelity, hierarchical vascularization with lymphatic-like drainage and mural cell integration, strategies for tissue innervation, and microscopic considerations including cellular heterogeneity or organoid-based assembly, etc. The scope of this call for submissions also encompasses applications in regenerative medicine, disease modeling, hybrid bio-inorganic constructs, as well as development of physiologically relevant culture systems for drug and toxicology testing, particularly in response to the need to reduce animal experimentation. By bringing together research articles, reviews, and perspectives, this Special Issue seeks not only to raise awareness, but also to establish benchmarks for biological realism in biofabrication, thus accelerating the transition to clinically relevant, biologically faithful tissue constructs for both in vivo and in vitro applications.

Dr. Nicanor Ilie Moldovan
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. Bioengineering 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 2700 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

  • biofabrication
  • biological realism
  • bioprinting
  • cell–biomaterial interaction
  • tissue engineering
  • hybrid constructs
  • clinical translation
  • in vitro models

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Published Papers (2 papers)

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25 pages, 9799 KB  
Article
Design and Validation of a Multi-Modal Bioreactor System: Assessing the Effects of Perfusion and Cyclic Tensile Stimulation on Mechanical and Biological Properties of 3D-Printed Missing-Rib Auxetic Scaffolds
by Tavila Sharmin, Sakhawat Hossan and Rohan A. Shirwaiker
Bioengineering 2026, 13(2), 140; https://doi.org/10.3390/bioengineering13020140 - 26 Jan 2026
Cited by 2 | Viewed by 1787
Abstract
Bioreactors used for the maturation of cell-seeded tissue-engineered scaffolds should essentially mimic the dynamic in vivo environments experienced by the native tissues they intend to substitute. In addition to perfusion of growth medium to facilitate continuous mass transfer, application of appropriate mechanical stimulation [...] Read more.
Bioreactors used for the maturation of cell-seeded tissue-engineered scaffolds should essentially mimic the dynamic in vivo environments experienced by the native tissues they intend to substitute. In addition to perfusion of growth medium to facilitate continuous mass transfer, application of appropriate mechanical stimulation is important to enhance cellular responses in scaffolds for tissues such as tendons, skin, and cardiac muscle that experience dynamic loading. This study focuses on the development of a multi-modal custom bioreactor capable of applying cyclic tensile stimulation and perfusion within physiologically relevant ranges while minimizing shear stress detrimental to cells seeded on scaffolds. To validate the bioreactor design and operation, we assessed the effects of tensile stimulation (0.1 Hz, 2000 cycles/day) and perfusion (media flow rate = 0.15 mL/min) over 21 days on the biofunctional performance of 3D-bioplotted polycaprolactone (PCL) auxetic scaffolds with a representative design (missing-rib pattern) characterized by negative Poisson’s ratio similar to the aforementioned soft tissues. The scaffold had a tensile yield strain of 9.14%, yield strength of 0.25 MPa, elastic modulus of 2.85 MPa, and ultimate tensile strength (UTS) of 1.32 MPa. The application of perfusion and tensile stimulation (0–5% cyclic strain) for 21 days did not adversely affect the yield strength and elastic modulus of the scaffold but affected its UTS (22.5% decrease) compared to the control cultured without perfusion or stimulation. Notably, it resulted in significantly improved fibroblast cellular responses (DNA = 29 µg/g sample and collagen = 371.78 µg/g sample) compared to the control (7.52 µg/g sample and 163.51 µg/g sample, respectively). These results validate the bioreactor system operation and the ability of multi-modal stimulation to control biofunctional responses of auxetic scaffolds, which will serve as the basis for future studies that will optimize auxetic scaffold design and dynamic culture parameters for NPR tissue-specific applications. Full article
(This article belongs to the Special Issue Biofabrication of Biologically Realistic Constructs: Needs, Challenges, and Opportunities)
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11 pages, 245 KB  
Opinion
Prospects and Limitations of Bioprinting in Studying Human Cells’ Responses to Extreme Environments
by Taieba Tuba Rahman, Zhijian Pei, Hongmin Qin and Hamid R. Parsaei
Bioengineering 2026, 13(4), 458; https://doi.org/10.3390/bioengineering13040458 - 14 Apr 2026
Viewed by 624
Abstract
Understanding human’s responses to extreme environments holds significant importance for space exploration, deep-sea research, and environmental adaptation. Traditionally, human subjects were used to study humans’ responses to extreme environments. The main limitations of this approach include the inability to independently investigate specific cellular [...] Read more.
Understanding human’s responses to extreme environments holds significant importance for space exploration, deep-sea research, and environmental adaptation. Traditionally, human subjects were used to study humans’ responses to extreme environments. The main limitations of this approach include the inability to independently investigate specific cellular mechanisms, ethical and safety constraints, limited experimental controllability, and inter-individual variability that complicates mechanistic interpretation. Another approach is to study humans’ responses at the cellular level using 2D culture. This approach often exhibits limited reproducibility due to its inability to recapitulate physiologically relevant microenvironments. Bioprinting can enable studies on human’s responses at the cellular level and within 3D environments. One way is to study human cells’ responses to localized and transient extreme environments created during printing. Another way is to expose 3D printed samples (embedded with human cells) to extreme environments. However, the literature does not contain comprehensive review papers to discuss the prospects and limitations of bioprinting for investigating human cells’ responses to extreme environments. This review paper aims to fill this gap in the literature. It begins with a brief description of the effects of extreme environments on human health and summarizes reported studies on cells’ responses to extreme environments. Afterward, it discusses the prospects and limitations of the two ways of using bioprinting to investigate cells’ responses to extreme environments. Finally, it concludes with identifying knowledge gaps and proposing research directions in the application of bioprinting to study human cells’ responses to extreme environments. Full article
(This article belongs to the Special Issue Biofabrication of Biologically Realistic Constructs: Needs, Challenges, and Opportunities)
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