bims-orenst 2022-01-23 papers

Issue of 2022–01–23
five papers selected by
Joram Mooiweer, University of Groningen

Nat Rev Rheumatol. 2022 Jan 20.

Joint-on-chip platforms: entering a new era of in vitro models for arthritis.

Carlo Alberto Paggi, Liliana Moreira Teixeira, Séverine Le Gac, Marcel Karperien.

Arthritis affects millions of people worldwide. With only a few disease-modifying drugs available for treatment of rheumatoid arthritis and none for osteoarthritis, a clear need exists for new treatment options. Current disease models used for drug screening and development suffer from several disadvantages and, most importantly, do not accurately emulate all facets of human joint diseases. A humanized joint-on-chip (JoC) model or platform could revolutionize research and drug development in rheumatic diseases. A JoC model is a multi-organ-on-chip platform that incorporates a range of engineered features to emulate essential aspects and functions of the human joint and faithfully recapitulates the joint's physiological responses. In this Review, we propose an architecture for such a JoC platform, discuss the status of the engineering of individual joint tissues and the efforts to combine them in a functional JoC model and identify unresolved issues and challenges in constructing an accurate, physiologically relevant system. The goal is to ultimately obtain a reliable and ready-to-use humanized model of the joint for studying the pathophysiology of rheumatic diseases and screening drugs for treatment of these conditions.

DOI: https://doi.org/10.1038/s41584-021-00736-6

Biofabrication. 2022 Jan 21.

Thin and stretchable extracellular matrix (ECM) membrane reinforced by nanofiber scaffolds for developing in vitro barrier models.

Jaeseung Youn, Hyeonjun Hong, Woojung Shin, Dohui Kim, Hyun Jung Kim, Dong Sung Kim.

An extracellular matrix (ECM) membrane made up of ECM hydrogels has great potentials to develop a physiologically relevant organ-on-a-chip because of its biochemical and biophysical similarity to in vivo basement membranes (BMs). However, the limited mechanical stability of the ECM hydrogels makes it difficult to utilize the ECM membrane in long-term and dynamic cell/tissue cultures. This study proposes an ultra-thin but robust and transparent ECM membrane reinforced with silk fibroin (SF)/polycaprolactone (PCL) nanofibers, which is achieved by in situ self-assembly throughout a freestanding SF/PCL nanofiber scaffold. The SF/PCL nanofiber-reinforced ECM (NaRE) membrane shows biophysical characteristics reminiscent of native BMs, including small thickness (< 5 μm), high permeability (< 9 × 10-5 cm s-1), and nanofibrillar architecture (~10 to 100 nm). With the BM-like characteristics, the nanofiber reinforcement ensured that the NaRE membrane stably supported the construction of various types of in vitro barrier models, from epithelial or endothelial barrier models to complex co-culture models, even over two weeks of cell culture periods. Furthermore, the stretchability of the NaRE membrane allowed emulating the native organ-like cyclic stretching motions (10 to 15%) and was demonstrated to manipulate the cell and tissue-level functions of the in vitro barrier model.

Keywords: Basement membrane; ECM membrane; Electrospun nanofiber; Extracellular matrix hydrogel; Organ-on-a-chip

DOI: https://doi.org/10.1088/1758-5090/ac4dd7

Bioengineering (Basel). 2022 Jan 11. pii: 28. [Epub ahead of print]9(1):

Organ on Chip Technology to Model Cancer Growth and Metastasis.

Giorgia Imparato, Francesco Urciuolo, Paolo Antonio Netti.

Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally reproduce certain key aspects of the tumor microenvironment (TME), such as biochemical gradients and niche factors, dynamic cell-cell and cell-matrix interactions, and complex tissue structures composed of tumor and stromal cells. Here, we review the state of the art in COC models with a focus on the microphysiological systems that host multicellular 3D tissue engineering models and can help elucidate the complex biology of TME and cancer growth and progression. Finally, some examples of microengineered tumor models integrated with multi-organ microdevices to study disease progression in different tissues will be presented.

Keywords: 3D tissue; cancer on chip; metastasis; organ on chip; tumor microenvironment

DOI: https://doi.org/10.3390/bioengineering9010028

Ann Biomed Eng. 2022 Jan 17.

Heart-on-Chip for Combined Cellular Dynamics Measurements and Computational Modeling Towards Clinical Applications.

Jiyoon Park, Ziqian Wu, Paul R Steiner, Bo Zhu, John X J Zhang.

Organ-on-chip or micro-engineered three-dimensional cellular or tissue models are increasingly implemented in the study of cardiovascular pathophysiology as alternatives to traditional in vitro cell culture. Drug induced cardiotoxicity is a key issue in drug development pipelines, but the current in vitro and in vivo studies suffer from inter-species differences, high costs, and lack of reliability and accuracy in predicting cardiotoxicity. Microfluidic heart-on-chip devices can impose a paradigm shift to the current tools. They can not only recapitulate cardiac tissue level functionality and the communication between cells and extracellular matrices but also allow higher throughput studies conducive to drug screening especially with their added functionalities or sensors that extract disease-specific phenotypic, genotypic, and electrophysiological information in real-time. Such electrical and mechanical components can tailor the electrophysiology and mechanobiology of the experiment to better mimic the in vivo condition as well. Recent advancements and challenges are reviewed in the fabrication, functionalization and sensor assisted mechanical and electrophysiological measurements, numerical and computational modeling of cardiomyocytes' behavior, and the clinical applications in drug screening and disease modeling. This review concludes with the current challenges and perspectives on the future of such organ-on-chip platforms.

Keywords: Cardiovascular disease modeling; Computational modeling; Drug screening; Heart-on-chip; Microfluidics

DOI: https://doi.org/10.1007/s10439-022-02902-7

Bioengineering (Basel). 2022 Jan 13. pii: 32. [Epub ahead of print]9(1):

A Bioprinted Heart-on-a-Chip with Human Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Evaluation.

Alan Faulkner-Jones, Victor Zamora, Maria P Hortigon-Vinagre, Wenxing Wang, Marcus Ardron, Godfrey L Smith, Wenmiao Shu.

In this work, we show that valve-based bioprinting induces no measurable detrimental effects on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The aim of the current study was three-fold: first, to assess the response of hiPSC-CMs to several hydrogel formulations by measuring electrophysiological function; second, to customise a new microvalve-based cell printing mechanism in order to deliver hiPSC-CMs suspensions, and third, to compare the traditional manual pipetting cell-culture method and cardiomyocytes dispensed with the bioprinter. To achieve the first and third objectives, iCell2 (Cellular Dynamics International) hiPSC-CMs were used. The effects of well-known drugs were tested on iCell2 cultured by manual pipetting and bioprinting. Despite the results showing that hydrogels and their cross-linkers significantly reduced the electrophysiological performance of the cells compared with those cultured on fibronectin, the bio-ink droplets containing a liquid suspension of live cardiomyocytes proved to be an alternative to standard manual handling and could reduce the number of cells required for drug testing, with no significant differences in drug-sensitivity between both approaches. These results provide a basis for the development of a novel bioprinter with nanolitre resolution to decrease the required number of cells and to automate the cell plating process.

Keywords: bio-ink; cell-printing; drug screening; hiPSC-CMs; hydrogels; in vitro testing; organs-on-a-chips

DOI: https://doi.org/10.3390/bioengineering9010032