Publications by authors named "Ilida Ortega Asencio"

7 Publications

  • Page 1 of 1

Delivery of Bioactive Compounds to Improve Skin Cell Responses on Microfabricated Electrospun Microenvironments.

Bioengineering (Basel) 2021 Jul 27;8(8). Epub 2021 Jul 27.

Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.

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.
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http://dx.doi.org/10.3390/bioengineering8080105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389211PMC
July 2021

Understanding Fibroblast Behavior in 3D Biomaterials.

Tissue Eng Part B Rev 2021 Aug 16. Epub 2021 Aug 16.

Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.

Traditional monolayer culture fails to fully recapitulate the environment of connective tissue cells such as the fibroblast. When cultured on stiff two-dimensional (2D) plastic, fibroblasts become highly proliferative forming broad lamellipodia and stress fibers. Conversely, in different three-dimensional (3D) culture systems, fibroblasts have displayed a diverse array of features; from an "activated" phenotype like that observed in 2D cultures and by myofibroblasts, to a quiescent state that likely better represents fibroblasts at rest. Today, a plethora of microfabrication techniques have made 3D culture commonplace, for both tissue engineering purposes and in the study of basic biological interactions. However, establishing the mimetic credentials of different biomimetic materials is not always straightforward, particularly in the context of fibroblast responses. Fibroblast behavior is governed by the complex interplay of biological features such as integrin binding sites, material mechanical properties that influence cellular mechanotransduction, and microarchitectural features like pore and fiber size, as well as chemical cues. Furthermore, fibroblasts are a heterogeneous group of cells with specific phenotypic traits dependent on their tissue of origin. These features have made understanding the influence of biomaterials on fibroblast behavior a challenging task. In this study, we present a review of the strategies used to investigate fibroblast behavior with a focus on the material properties that influence fibroblast activation, a process that becomes pathological in fibrotic diseases and certain cancers.
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http://dx.doi.org/10.1089/ten.TEB.2021.0010DOI Listing
August 2021

The Use of Microfabrication Techniques for the Design and Manufacture of Artificial Stem Cell Microenvironments for Tissue Regeneration.

Bioengineering (Basel) 2021 Apr 23;8(5). Epub 2021 Apr 23.

Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.

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.
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http://dx.doi.org/10.3390/bioengineering8050050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146165PMC
April 2021

Fabrication of Topographically Controlled Electrospun Scaffolds to Mimic the Stem Cell Microenvironment in the Dermal-Epidermal Junction.

ACS Biomater Sci Eng 2021 06 27;7(6):2803-2813. Epub 2021 Apr 27.

Bioengineering and Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, U.K.

The use of microfabrication techniques for the development of innovative constructs for tissue regeneration is a growing area of research. This area comprises both manufacturing and biological approaches for the development of smart materials aiming to control and direct cell behavior to enhance tissue healing. Many groups have focused their efforts on introducing complexity within these innovative constructs via the inclusion of nano- and microtopographical cues mimicking physical and biological aspects of the native stem cell niche. Specifically, in the area of skin tissue engineering, seminal work has reported replicating the microenvironments located in the dermal-epithelial junction, which are known as rete ridges. The rete ridges are key for both stem cell control and the physiological performance of the skin. In this work, we have introduced complexity within electrospun membranes to mimic the morphology of the rete ridges in the skin. We designed and tested three different patterns, characterized them, and explored their performance in vitro, using 3D skin models. One of the studied patterns (pattern B) was shown to aid in the development of an in vitro rite-ridgelike skin model that resulted in the expression of relevant epithelial markers such as collagen IV and integrin β1. In summary, we have developed a new skin model including synthetic rete-ridgelike structures that replicate both morphology and function of the native dermal-epidermal junction and that offer new insights for the development of smart skin tissue engineering constructs.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01775DOI Listing
June 2021

The Emerging Potential of Extracellular Vesicles in Cell-Free Tissue Engineering and Regenerative Medicine.

Tissue Eng Part B Rev 2020 Dec 3. Epub 2020 Dec 3.

School of Clinical Dentistry, The University of Sheffield, Sheffield, United Kingdom.

Extracellular vesicles (Evs) are membrane-enclosed vesicles secreted by all cell types that mediate cell-cell communication via their protein, lipid, carbohydrate, and nucleic acid (RNA, DNA) cargo. EVs are involved in a multitude of physiological processes, including development, cell differentiation, and angiogenesis, and have been implicated in tissue repair. Thus, they have been suggested to offer opportunities for the development of novel cell-free tissue engineering (TE) approaches. In this review, we provide an overview of current understanding and emerging applications of EVs in TE and address opportunities and challenges for clinical translation. In addition, we discuss systemic and local routes of delivery of EVs and the advantages and disadvantages of different biomaterials in providing a substrate for the sustained release of EVs . Impact statement Extracellular vesicles (EVs) are nanoscale, membrane-bound vesicles released by most, if not all, cells in the body. They are implicated in a wide range of physiological processes and diseases ranging from cancer to neurodegeneration, and hold huge potential as mediators of tissue regeneration. This has led to an explosion of interest in using EVs in a variety of tissue engineering applications. In this review, we provide an overview of current progress in the field and highlight the opportunities and challenges of harnessing the potential of EVs in regenerative medicine.
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http://dx.doi.org/10.1089/ten.TEB.2020.0222DOI Listing
December 2020

A methodology for the production of microfabricated electrospun membranes for the creation of new skin regeneration models.

J Tissue Eng 2018 Jan-Dec;9:2041731418799851. Epub 2018 Sep 21.

Biomaterials and Tissue Engineering Group, Department of Materials Science and Engineering, Kroto Research Institute, The University of Sheffield, Sheffield, UK.

The continual renewal of the epidermis is thought to be related to the presence of populations of epidermal stem cells residing in physically protected microenvironments (rete ridges) directly influenced by the presence of mesenchymal fibroblasts. Current skin in vitro models do acknowledge the influence of stromal fibroblasts in skin reorganisation but the study of the effect of the rete ridge-microenvironment on epidermal renewal still remains a rich topic for exploration. We suggest there is a need for the development of new in vitro models in which to study epithelial stem cell behaviour prior to translating these models into the design of new cell-free biomaterial devices for skin reconstruction. In this study, we aimed to develop new prototype epidermal-like layers containing pseudo-rete ridge structures for studying the effect of topographical cues on epithelial cell behaviour. The models were designed using a range of three-dimensional electrospun microfabricated scaffolds. This was achieved via the utilisation of polyethylene glycol diacrylate to produce a reusable template over which poly(3-hydrroxybutyrate--3-hydroxyvalerate) was electrospun. Initial investigations studied the behaviour of keratinocytes cultured on models using plain scaffolds (without the presence of intricate topography) versus keratinocytes cultured on scaffolds containing microfeatures.
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http://dx.doi.org/10.1177/2041731418799851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153546PMC
September 2018

Selective laser melting-enabled electrospinning: Introducing complexity within electrospun membranes.

Proc Inst Mech Eng H 2017 Jun;231(6):565-574

Bioengineering and Health Technologies Group, The School of Clinical Dentistry, The University of Sheffield, Sheffield, UK.

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing.
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http://dx.doi.org/10.1177/0954411917690182DOI Listing
June 2017
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