Author
Dallin J. Jacobs
Bio: Dallin J. Jacobs is an academic researcher from Brigham Young University. The author has contributed to research in topics: Extracellular matrix & Tissue engineering. The author has an hindex of 1, co-authored 3 publications receiving 1 citations.
Papers
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TL;DR: The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival, and the use of ECM and ECM-like scaffolds has separated the field into two distinct areas.
Abstract: The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival. In tissue engineering, the use of ECM and ECM-like scaffolds has separated the field into two distinct areas—scaffold-based and scaffold-free. Scaffold-free techniques are used in creating reproducible cell aggregates which have massive potential for high-throughput, reproducible drug screening and disease modeling. Though, the lack of ECM prevents certain cells from surviving and proliferating. Thus, tissue engineers use scaffolds to mimic the native ECM and produce organotypic models which show more reliability in disease modeling. However, scaffold-based techniques come at a trade-off of reproducibility and throughput. To bridge the tissue engineering dichotomy, we posit that finding novel ways to incorporate the ECM in scaffold-free cultures can synergize these two disparate techniques.
33 citations
TL;DR: In this article, a viable lung organoid from epithelial, endothelial, and fibroblast stable cell lines in suspension culture supplemented with soluble concentrations of extracellular matrix proteins (ECM).
Abstract: Scaffold-free tissue engineering is desired in creating consistently sized and shaped cell aggregates but has been limited to spheroid-like structure and function, thus restricting its use in accurate disease modeling. Here, we show formation of a viable lung organoid from epithelial, endothelial, and fibroblast stable cell lines in suspension culture supplemented with soluble concentrations of extracellular matrix proteins (ECM). We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of air space-like gas exchange units, formation of branching, perfusable vasculature, and increased 3D growth. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. Endothelial branching was found to depend on both soluble ECM and fibroblast. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model accurately represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.
6 citations
TL;DR: In this paper, a scalable hydrogel dish design was proposed to facilitate scaffold-free formation of multiple spheroids in a single dish, with inner and outer walls, allowing efficient media changes and downstream experiments.
Abstract: Research in fields studying cellular response to surface tension and mechanical forces necessitate cell culture tools with tunability of substrate stiffness. We created a scalable hydrogel dish design to facilitate scaffold-free formation of multiple spheroids in a single dish. Our novel design features inner and outer walls, allowing efficient media changes and downstream experiments. The design is easily scalable, accommodating varying numbers of microwells per plate. We report that non-adherent hydrogel stiffness affects spheroid morphology and compaction. We found that spheroid morphology and viability in our hydrogel dishes were comparable to commercially available Aggrewell™800 plates, with improved tunability of surface stiffness and imaging area. Device function was demonstrated with a migration assay using two investigational inhibitors against EMT. We successfully maintained primary-derived spheroids from murine and porcine lungs in the hydrogel dish. These features increase the ability to produce highly consistent cell aggregates for biological research.
6 citations
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TL;DR: In this article , the state of the art of the utilization of bio-inks based on natural polymers (biopolymers), such as cellulose, agarose, alginate, decellularized matrix, in 3D bioprinting is explored.
Abstract: Three-dimensional (3D) printing is well acknowledged to constitute an important technology in tissue engineering, largely due to the increasing global demand for organ replacement and tissue regeneration. In 3D bioprinting, which is a step ahead of 3D biomaterial printing, the ink employed is impregnated with cells, without compromising ink printability. This allows for immediate scaffold cellularization and generation of complex structures. The use of cell-laden inks or bio-inks provides the opportunity for enhanced cell differentiation for organ fabrication and regeneration. Recognizing the importance of such bio-inks, the current study comprehensively explores the state of the art of the utilization of bio-inks based on natural polymers (biopolymers), such as cellulose, agarose, alginate, decellularized matrix, in 3D bioprinting. Discussions regarding progress in bioprinting, techniques and approaches employed in the bioprinting of natural polymers, and limitations and prospects concerning future trends in human-scale tissue and organ fabrication are also presented.
54 citations
TL;DR: In this paper , a review outlines the recent advances in the fabrication of chitosan-based scaffolds as a pharmaceutical carrier to deliver drugs such as antibiotics, growth factors, nucleic acids, and phenolic compounds for bone tissue regeneration.
14 citations
TL;DR: A review of recent studies that utilize engineered biomaterials to guide spheroid formation and function, as well as their fabrication into tissues for use as tissue models and for therapeutic applications can be found in this paper .
11 citations
TL;DR: A review of lung stem cell research can be found in this article , where the authors trace the known stages and pathways involved in in vivo lung development and how they inspire the directed differentiation of stem and progenitor cells in vitro.
Abstract: The global burden of pulmonary disease highlights an overwhelming need in improving our understanding of lung development, disease, and treatment. It also calls for further advances in our ability to engineer the pulmonary system at cellular and tissue levels. The discovery of human pluripotent stem cells (hPSCs) offsets the relative inaccessibility of human lungs for studying developmental programs and disease mechanisms, all the while offering a potential source of cells and tissue for regenerative interventions. This review offers a perspective on where the lung stem cell field stands in terms of accomplishing these ambitious goals. We will trace the known stages and pathways involved in in vivo lung development and how they inspire the directed differentiation of stem and progenitor cells in vitro. We will also recap the efforts made to date to recapitulate the lung stem cell niche in vitro via engineered cell-cell and cell-extracellular matrix (ECM) interactions.
6 citations
TL;DR: In this article, a viable lung organoid from epithelial, endothelial, and fibroblast stable cell lines in suspension culture supplemented with soluble concentrations of extracellular matrix proteins (ECM).
Abstract: Scaffold-free tissue engineering is desired in creating consistently sized and shaped cell aggregates but has been limited to spheroid-like structure and function, thus restricting its use in accurate disease modeling. Here, we show formation of a viable lung organoid from epithelial, endothelial, and fibroblast stable cell lines in suspension culture supplemented with soluble concentrations of extracellular matrix proteins (ECM). We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of air space-like gas exchange units, formation of branching, perfusable vasculature, and increased 3D growth. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. Endothelial branching was found to depend on both soluble ECM and fibroblast. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model accurately represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.
6 citations