Tissue specific microenvironments: a key tool for tissue engineering and regenerative medicine

Sachs, Patrick C.; Mollica, Peter A.; Bruno, Robert D.

doi:10.1186/s13036-017-0077-0

Cited by 35 publications

(27 citation statements)

References 117 publications

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“…More importantly, using this system to investigate co-cultures of two or more cell types in a defined microenvironment would greatly increase the ability to develop reliable 3D surrogate models for breast development and carcinogenesis. This is of particular interest to our group, as we have great interest in understanding how the microenvironment controls differentiation of stem and cancer cells [ 36 – 45 ]. We plan to adapt these protocols for the development of chimeric structures containing cancer and normal epithelial cells as in vitro models that mimic our previous in vivo findings.…”

Section: Discussionmentioning

confidence: 99%

Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform

et al. 2018

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BackgroundStandard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.MethodsHere, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the “self-assembly” of human mammary epithelial cells. Experimental bioprinting procedures were optimized to enable the formation of controlled arrays of individual mammary organoids. We define the distance and cell number parameters necessary to print individual organoids that do not interact between print locations as well as those required to generate large contiguous organoids connected through multiple print locations.ResultsWe demonstrate that as few as 10 cells can be used to form 3D mammary structures in a single print and that prints up to 500 μm apart can fuse to form single large structures. Using these fusion parameters, we demonstrate that both linear and non-linear (contiguous circles) can be generated with sizes of 3 mm in length/diameter. We confirm that cells from individual prints interact to form structures with a contiguous lumen. Finally, we demonstrate that organoids can be printed into human collagen hydrogels, allowing for all-human 3D culture systems.ConclusionsOur platform is adaptable to different culturing protocols and is superior to traditional random 3D culture techniques in efficiency, reproducibility, and scalability. Importantly, owing to the low-cost accessibility and computer numerical control–driven platform of our 3D bioprinter, we have the ability to disseminate our experiments with absolute precision to interested laboratories.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1045-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform

et al. 2018

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“…The ability to recapitulate and investigate complex signaling interactions between constituent cells and their surrounding microenvironment is crucial to elucidating the biological processes that underlie both normal mammalian tissue function and pathological dysfunction (1)(2)(3). Soluble cues, cell-cell contact-dependent signals, and "solidphase" matrix cues coordinate across space and time to encode and transmit regulatory information to instruct single-cell behavior (4).…”

Section: Introductionmentioning

confidence: 99%

Recapitulating complex biological signaling environments using a multiplexed, DNA-patterning approach

et al. 2020

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Elucidating how the spatial organization of extrinsic signals modulates cell behavior and drives biological processes remains largely unexplored because of challenges in controlling spatial patterning of multiple microenvironmental cues in vitro. Here, we describe a high-throughput method that directs simultaneous assembly of multiple cell types and solid-phase ligands across length scales within minutes. Our method involves lithographically defining hierarchical patterns of unique DNA oligonucleotides to which complementary strands, attached to cells and ligands-of-interest, hybridize. Highlighting our method's power, we investigated how the spatial presentation of self-renewal ligand fibroblast growth factor-2 (FGF-2) and differentiation signal ephrin-B2 instruct single adult neural stem cell (NSC) fate. We found that NSCs have a strong spatial bias toward FGF-2 and identified an unexpected subpopulation exhibiting high neuronal differentiation despite spatially occupying patterned FGF-2 regions. Overall, our broadly applicable, DNA-directed approach enables mechanistic insight into how tissues encode regulatory information through the spatial presentation of heterogeneous signals.

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“…In recent years, remarkable advancements in biomaterials science and the development of powerful biofabrication techniques, have enabled the engineering of artificial human tissues that possess an unprecedented level of physiological relevance [21][22][23]. Tissue engineering (TE) has enabled the development of custom biomimetic tissues, which have served as models for a plethora of applications in pharmaceutics [24][25][26], regenerative medicine [27,28], diagnostics [29], as well as fundamental research to elucidate the mechanisms that underlie disease onset and progression [4,30,31].…”

Section: Introductionmentioning

confidence: 99%

Biomimetic cardiovascular platforms for in vitro disease modeling and therapeutic validation

et al. 2019

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Bioengineered tissues have become increasingly more sophisticated owing to recent advancements in the fields of biomaterials, microfabrication, microfluidics, genetic engineering, and stem cell and developmental biology. In the coming years, the ability to engineer artificial constructs that accurately mimic the compositional, architectural, and functional properties of human tissues, will profoundly impact the therapeutic and diagnostic aspects of the healthcare industry. In this regard, bioengineered cardiac tissues are of particular importance due to the extremely limited ability of the myocardium to self-regenerate, as well as the remarkably high mortality associated with cardiovascular diseases worldwide. As novel microphysiological systems make the transition from bench to bedside, their implementation in high throughput drug screening, personalized diagnostics, disease modeling, and targeted therapy validation will bring forth a paradigm shift in the clinical management of cardiovascular diseases. Here, we will review the current state of the art in experimental in vitro platforms for next generation diagnostics and therapy validation. We will describe recent advancements in the development of smart biomaterials, biofabrication techniques, and stem cell engineering, aimed at recapitulating cardiovascular function at the tissue- and organ levels. In addition, integrative and multidisciplinary approaches to engineer biomimetic cardiovascular constructs with unprecedented human and clinical relevance will be discussed. We will comment on the implementation of these platforms in high throughput drug screening, in vitro disease modeling and therapy validation. Lastly, future perspectives will be provided on how these biomimetic platforms will aid in the transition towards patient centered diagnostics, and the development of personalized targeted therapeutics.

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Tissue specific microenvironments: a key tool for tissue engineering and regenerative medicine

Cited by 35 publications

References 117 publications

Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform

Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform

Recapitulating complex biological signaling environments using a multiplexed, DNA-patterning approach

Biomimetic cardiovascular platforms for in vitro disease modeling and therapeutic validation

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