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Bioengineering
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Design and Fabrication of Artificial Stem Cell Microenvironments
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Design and Fabrication of Artificial Stem Cell Microenvironments

A special issue of Bioengineering (ISSN 2306-5354).

Deadline for manuscript submissions: closed (4 June 2021) | Viewed by 32852

Special Issue Editors

Dr. Ilida Ortega Asencio

E-Mail Website
Guest Editor
School of Clinical Dentistry, The University of Sheffield, Sheffield S10 2TN, UK
Interests: stem cell niche; biomaterial design; tissue regeneration; synthetic microenvironment; microfabrication; biofunctionalisation
Special Issues, Collections and Topics in MDPI journals
Dr. Farshid Sefat

E-Mail Website
Guest Editor
Faculty of Engineering and Informatics, Biomedical and Electronics Engineering Department, University of Bradford, Bradford BD7 1DP, UK
Interests: biomaterials design; processing; testing and development; cell and tissue engineering; electrospinning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is well-known that the native stem cell niche plays a key role in dictating stem cell fate and that being able to recapitulate specific features of such intricate environment can open the door to the development of more efficient biomaterials for tissue regeneration applications. Many research groups are now directing their efforts towards the design and manufacture of topographically controlled biomaterials that are able to mimic different aspects of the native stem cell niche, looking at both the niche physical/spatial distribution as well as its biochemical/ biomechanical conformation. This special issue is focused on the “Design and Fabrication of Artificial Stem Cell Niches” and it aims to capture innovative approaches to designing functional synthetic niche environments in a form of original research papers as well as comprehensive reviews.

Dr. Ilida Ortega Asencio
Dr. Farshid Sefat
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • Stem Cell Niche
  • Biomaterial Design
  • Tissue Regeneration
  • Synthetic Microenvironment
  • Microfabrication
  • Biofunctionalisation

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Published Papers (8 papers)

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Editorial

Jump to: Research, Review

3 pages, 191 KiB  
Editorial
Design and Fabrication of Artificial Stem Cell Niches
by Tiago G. Fernandes
Bioengineering 2022, 9(12), 813; https://doi.org/10.3390/bioengineering9120813 - 16 Dec 2022
Cited by 2 | Viewed by 1348
Abstract
The term “cellular microenvironment” is a generic expression used to describe the complex collection of stimuli that contribute to cell and tissue functions [...] Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
6 pages, 578 KiB  
Editorial
Design and Fabrication of Artificial Stem Cell Microenvironments
by Panagiotis Mallis
Bioengineering 2022, 9(12), 756; https://doi.org/10.3390/bioengineering9120756 - 2 Dec 2022
Viewed by 1148
Abstract
Major key features of stem cells’ functions are self-renewal and their capacity for differentiation, allowing for maintain a proper stem cell reservoir as well as producing lineage-committed cells [...] Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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Research

Jump to: Editorial, Review

18 pages, 5011 KiB  
Article
Modulation of Synthetic Tracheal Grafts with Extracellular Matrix Coatings
by Lumei Liu, Sayali Dharmadhikari, Robert A. Pouliot, Michael M. Li, Peter M. Minneci, Zhenghong Tan, Kimberly Shontz, Jed Johnson, Susan D. Reynolds, Christopher K. Breuer, Daniel J. Weiss and Tendy Chiang
Bioengineering 2021, 8(8), 116; https://doi.org/10.3390/bioengineering8080116 - 20 Aug 2021
Cited by 6 | Viewed by 3036
Abstract
Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates [...] Read more.
Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates (pECM and hECM) were created through the decellularization and lyophilization of lung tissue. Four concentrations of pECM and hECM coatings on syn-TG were characterized for their effects on scaffold morphologies and on in vitro cell viability and growth. Uncoated and ECM-coated syn-TG were subsequently evaluated in vivo through the orthotopic implantation of segmental grafts or patches. These studies demonstrated that ECM coatings were not cytotoxic and, enhanced the in vitro cell viability and growth on syn-TG in a dose-dependent manner. Mass spectrometry demonstrated that fibrillin, collagen, laminin, and nephronectin were the predominant ECM components transferred onto scaffolds. The in vivo results exhibited similar robust epithelialization of uncoated and coated syn-TG patches; however, the epithelialization remained poor with either uncoated or coated scaffolds in the segmental replacement models. Overall, these findings demonstrated that ECM coatings improve the seeded cell biocompatibility of synthetic scaffolds in vitro; however, they do not improve graft epithelialization in vivo. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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19 pages, 6210 KiB  
Article
Delivery of Bioactive Compounds to Improve Skin Cell Responses on Microfabricated Electrospun Microenvironments
by David H. Ramos-Rodriguez, Sheila MacNeil, Frederik Claeyssens and Ilida Ortega Asencio
Bioengineering 2021, 8(8), 105; https://doi.org/10.3390/bioengineering8080105 - 27 Jul 2021
Cited by 11 | Viewed by 3536
Abstract
The introduction of microtopographies within biomaterial devices is a promising approach that allows one to replicate to a degree the complex native environment in which human cells reside. Previously, our group showed that by combining electrospun fibers and additive manufacturing it is possible [...] Read more.
The introduction of microtopographies within biomaterial devices is a promising approach that allows one to replicate to a degree the complex native environment in which human cells reside. Previously, our group showed that by combining electrospun fibers and additive manufacturing it is possible to replicate to an extent the stem cell microenvironment (rete ridges) located between the epidermal and dermal layers. Our group has also explored the use of novel proangiogenic compounds to improve the vascularization of skin constructs. Here, we combine our previous approaches to fabricate innovative polycaprolactone fibrous microtopographical scaffolds loaded with bioactive compounds (2-deoxy-D-ribose, 17β-estradiol, and aloe vera). Metabolic activity assay showed that microstructured scaffolds can be used to deliver bioactive agents and that the chemical relation between the working compound and the electrospinning solution is critical to replicate as much as possible the targeted morphologies. We also reported that human skin cell lines have a dose-dependent response to the bioactive compounds and that their inclusion has the potential to improve cell activity, induce blood vessel formation and alter the expression of relevant epithelial markers (collagen IV and integrin β1). In summary, we have developed fibrous matrixes containing synthetic rete-ridge-like structures that can deliver key bioactive compounds that can enhance skin regeneration and ultimately aid in the development of a complex wound healing device. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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Review

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42 pages, 6659 KiB  
Review
Biofabrication of Artificial Stem Cell Niches in the Anterior Ocular Segment
by Veronica Hidalgo-Alvarez, Hala S. Dhowre, Olivia A. Kingston, Carl M. Sheridan and Hannah J. Levis
Bioengineering 2021, 8(10), 135; https://doi.org/10.3390/bioengineering8100135 - 30 Sep 2021
Cited by 7 | Viewed by 6803
Abstract
The anterior segment of the eye is a complex set of structures that collectively act to maintain the integrity of the globe and direct light towards the posteriorly located retina. The eye is exposed to numerous physical and environmental insults such as infection, [...] Read more.
The anterior segment of the eye is a complex set of structures that collectively act to maintain the integrity of the globe and direct light towards the posteriorly located retina. The eye is exposed to numerous physical and environmental insults such as infection, UV radiation, physical or chemical injuries. Loss of transparency to the cornea or lens (cataract) and dysfunctional regulation of intra ocular pressure (glaucoma) are leading causes of worldwide blindness. Whilst traditional therapeutic approaches can improve vision, their effect often fails to control the multiple pathological events that lead to long-term vision loss. Regenerative medicine approaches in the eye have already had success with ocular stem cell therapy and ex vivo production of cornea and conjunctival tissue for transplant recovering patients’ vision. However, advancements are required to increase the efficacy of these as well as develop other ocular cell therapies. One of the most important challenges that determines the success of regenerative approaches is the preservation of the stem cell properties during expansion culture in vitro. To achieve this, the environment must provide the physical, chemical and biological factors that ensure the maintenance of their undifferentiated state, as well as their proliferative capacity. This is likely to be accomplished by replicating the natural stem cell niche in vitro. Due to the complex nature of the cell microenvironment, the creation of such artificial niches requires the use of bioengineering techniques which can replicate the physico-chemical properties and the dynamic cell–extracellular matrix interactions that maintain the stem cell phenotype. This review discusses the progress made in the replication of stem cell niches from the anterior ocular segment by using bioengineering approaches and their therapeutic implications. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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29 pages, 7773 KiB  
Review
Stem Cell Niche Microenvironment: Review
by Mohamed Abdul-Al, George Kumi Kyeremeh, Morvarid Saeinasab, Saeed Heidari Keshel and Farshid Sefat
Bioengineering 2021, 8(8), 108; https://doi.org/10.3390/bioengineering8080108 - 28 Jul 2021
Cited by 19 | Viewed by 4998
Abstract
The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live [...] Read more.
The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN and artificial stem cells for self-renewal. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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13 pages, 1384 KiB  
Review
Hematopoietic Stem Cells: Nature and Niche Nurture
by Geoffrey Brown
Bioengineering 2021, 8(5), 67; https://doi.org/10.3390/bioengineering8050067 - 15 May 2021
Cited by 2 | Viewed by 4509
Abstract
Like all cells, hematopoietic stem cells (HSCs) and their offspring, the hematopoietic progenitor cells (HPCs), are highly sociable. Their capacity to interact with bone marrow niche cells and respond to environmental cytokines orchestrates the generation of the different types of blood and immune [...] Read more.
Like all cells, hematopoietic stem cells (HSCs) and their offspring, the hematopoietic progenitor cells (HPCs), are highly sociable. Their capacity to interact with bone marrow niche cells and respond to environmental cytokines orchestrates the generation of the different types of blood and immune cells. The starting point for engineering hematopoiesis ex vivo is the nature of HSCs, and a longstanding premise is that they are a homogeneous population of cells. However, recent findings have shown that adult bone marrow HSCs are really a mixture of cells, with many having lineage affiliations. A second key consideration is: Do HSCs “choose” a lineage in a random and cell-intrinsic manner, or are they instructed by cytokines? Since their discovery, the hematopoietic cytokines have been viewed as survival and proliferation factors for lineage committed HPCs. Some are now known to also instruct cell lineage choice. These fundamental changes to our understanding of hematopoiesis are important for placing niche support in the right context and for fabricating an ex vivo environment to support HSC development. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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21 pages, 1978 KiB  
Review
The Use of Microfabrication Techniques for the Design and Manufacture of Artificial Stem Cell Microenvironments for Tissue Regeneration
by David H. Ramos-Rodriguez, Sheila MacNeil, Frederik Claeyssens and Ilida Ortega Asencio
Bioengineering 2021, 8(5), 50; https://doi.org/10.3390/bioengineering8050050 - 23 Apr 2021
Cited by 11 | Viewed by 5860
Abstract
The recapitulation of the stem cell microenvironment is an emerging area of research that has grown significantly in the last 10 to 15 years. Being able to understand the underlying mechanisms that relate stem cell behavior to the physical environment in which stem [...] Read more.
The recapitulation of the stem cell microenvironment is an emerging area of research that has grown significantly in the last 10 to 15 years. Being able to understand the underlying mechanisms that relate stem cell behavior to the physical environment in which stem cells reside is currently a challenge that many groups are trying to unravel. Several approaches have attempted to mimic the biological components that constitute the native stem cell niche, however, this is a very intricate environment and, although promising advances have been made recently, it becomes clear that new strategies need to be explored to ensure a better understanding of the stem cell niche behavior. The second strand in stem cell niche research focuses on the use of manufacturing techniques to build simple but functional models; these models aim to mimic the physical features of the niche environment which have also been demonstrated to play a big role in directing cell responses. This second strand has involved a more engineering approach in which a wide set of microfabrication techniques have been explored in detail. This review aims to summarize the use of these microfabrication techniques and how they have approached the challenge of mimicking the native stem cell niche. Full article
(This article belongs to the Special Issue Design and Fabrication of Artificial Stem Cell Microenvironments)
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