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Bioengineering
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Extracellular Matrix in Wound Healing
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Extracellular Matrix in Wound Healing

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

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 34099

Special Issue Editors

Prof. Dr. Donald Freytes

E-Mail Website1 Website2
Guest Editor
The University of North Carolina at Chapel Hill, Joint Department of Biomedical Engineering, Chapel Hill, United States
Interests: Human pluripotent stem cells differentiation; Modeling inflammation and macrophage polarization; Studying interactions between tissue engineered devices and the host tissue response
Special Issues, Collections and Topics in MDPI journals
Dr. Camilo Mora-Navarro

E-Mail Website
Guest Editor
Joint Department of Biomedical Engineering, NC State/ UNC-Chapel Hill
Interests: Tissue engineering scaffolds that positively modulate the wound healing host response; cell therapy in combination with scaffold materials; macrovesicle carriers; and antimicrobial agents’ development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The derivation of tissue-specific extracellular matrix scaffolds (ECM-scaffold) and the use of ECM components to produce novel biomaterials represent an exciting approach since it relies on the natural design and the unique composition of the tissues. If the ECM-scaffold is derived with minimal processing to yield an implantable material with low DNA content procuring a low immunogenicity risk, it should retain important cell cues and tissue signaling molecules that help to modulate cell behavior in vitro and promote healing during the host tissue response in vivo. Moreover, extracellular matrix components are integral to each phase of the wound healing process, interacting with cells and growth factors in a dynamic give-and-take that eventually could result in constructive remodeling of the injury. Although the clinical utility of ECM-scaffolds has been well established, the biological reasons for such host responses remain elusive. Therefore, understanding the mechanism behind the cellular recognition that leads to a specific cellular response in vivo and in vitro will expand our understanding of the clinical success and failures observed with these biomaterials. It would also help to improve current decellularization protocols or novel biomanufacturing processes, such as 3D printing, that could lead to superior biomaterials and enhance healing and constructive remodeling.

The Special Issue will focus on mechanistic studies looking at:

  • Derivation of tissue-specific ECM scaffolds with an emphasis on mechanistic reasons for the enhanced tissue response;
  • Compositional analysis and comparisons of ECM scaffolds;
  • Use of ECM-scaffolds to create in vitro testing platforms;
  • Role of tissue specificity on stem cell differentiation in vitro;
  • Role of tissue specificity on host tissue response;
  • ECM-scaffold directed stem cell differentiation;
  • Mechanism for macrophage polarization in vitro and in vivo;
  • Mechanisms for scar tissue inhibition;
  • Role of ECM during healing and tissue regeneration;
  • Use of tissue-specific ECM components to create novel biomaterials;
  • Use of novel biomanufacturing processes using ECM components;
  • Use of Polymer-Extracellular-Matrix composites in wound healing;
  • Guided deposition of ECM during the healing response using novel biomaterials therapeutic strategies.

Prof. Dr. Donald Freytes
Dr. Camilo Mora-Navarro
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.

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Published Papers (4 papers)

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Research

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14 pages, 5748 KiB  
Article
Micropatterning Decellularized ECM as a Bioactive Surface to Guide Cell Alignment, Proliferation, and Migration
by Emily Cady, Jacob A. Orkwis, Rachel Weaver, Lia Conlin, Nicolas N. Madigan and Greg M. Harris
Bioengineering 2020, 7(3), 102; https://doi.org/10.3390/bioengineering7030102 - 31 Aug 2020
Cited by 12 | Viewed by 4860
Abstract
Bioactive surfaces and materials have displayed great potential in a variety of tissue engineering applications but often struggle to completely emulate complex bodily systems. The extracellular matrix (ECM) is a crucial, bioactive component in all tissues and has recently been identified as a [...] Read more.
Bioactive surfaces and materials have displayed great potential in a variety of tissue engineering applications but often struggle to completely emulate complex bodily systems. The extracellular matrix (ECM) is a crucial, bioactive component in all tissues and has recently been identified as a potential solution to be utilized in combination with biomaterials. In tissue engineering, the ECM can be utilized in a variety of applications by employing the biochemical and biomechanical cues that are crucial to regenerative processes. However, viable solutions for maintaining the dimensionality, spatial orientation, and protein composition of a naturally cell-secreted ECM remain challenging in tissue engineering. Therefore, this work used soft lithography to create micropatterned polydimethylsiloxane (PDMS) substrates of a three-dimensional nature to control cell adhesion and alignment. Cells aligned on the micropatterned PDMS, secreted and assembled an ECM, and were decellularized to produce an aligned matrix biomaterial. The cells seeded onto the decellularized, patterned ECM showed a high degree of alignment and migration along the patterns compared to controls. This work begins to lay the groundwork for elucidating the immense potential of a natural, cell-secreted ECM for directing cell function and offers further guidance for the incorporation of natural, bioactive components for emerging tissue engineering technologies. Full article
(This article belongs to the Special Issue Extracellular Matrix in Wound Healing)
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18 pages, 3069 KiB  
Article
Coupling of Fibrin Reorganization and Fibronectin Patterning by Corneal Fibroblasts in Response to PDGF BB and TGFβ1
by Miguel Miron-Mendoza, Dalia Vazquez, Nerea García-Rámila, Hikaru R. Ikebe and W. Matthew Petroll
Bioengineering 2020, 7(3), 89; https://doi.org/10.3390/bioengineering7030089 - 7 Aug 2020
Cited by 8 | Viewed by 4228
Abstract
We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this [...] Read more.
We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell-induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGFβ1 stimulated global fibrin matrix contraction (p < 0.005); however, the cell and matrix patterning were different. We found that, during PDGF BB-induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (p < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (p < 0.001). Taken together, our results show that cell-induced extracellular matrix (ECM) reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery. Full article
(This article belongs to the Special Issue Extracellular Matrix in Wound Healing)
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19 pages, 7892 KiB  
Article
Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair
by Jiranuwat Sapudom, Walaa Kamal E. Mohamed, Anna Garcia-Sabaté, Aseel Alatoom, Shaza Karaman, Nikhil Mahtani and Jeremy C. M. Teo
Bioengineering 2020, 7(2), 33; https://doi.org/10.3390/bioengineering7020033 - 31 Mar 2020
Cited by 44 | Viewed by 18153
Abstract
Monocytes circulate in the bloodstream, extravasate into the tissue and differentiate into specific macrophage phenotypes to fulfill the immunological needs of tissues. During the tissue repair process, tissue density transits from loose to dense tissue. However, little is known on how changes in [...] Read more.
Monocytes circulate in the bloodstream, extravasate into the tissue and differentiate into specific macrophage phenotypes to fulfill the immunological needs of tissues. During the tissue repair process, tissue density transits from loose to dense tissue. However, little is known on how changes in tissue density affects macrophage activation and their cellular functions. In this work, monocytic cell line THP-1 cells were embedded in three-dimensional (3D) collagen matrices with different fibril density and were then differentiated into uncommitted macrophages (MPMA) using phorbol-12-myristate-13-acetate (PMA). MPMA macrophages were subsequently activated into pro-inflammatory macrophages (MLPS/IFNγ) and anti-inflammatory macrophages (MIL-4/IL-13) using lipopolysaccharide and interferon-gamma (IFNγ), and interleukin 4 (IL-4) and IL-13, respectively. Although analysis of cell surface markers, on both gene and protein levels, was inconclusive, cytokine secretion profiles, however, demonstrated differences in macrophage phenotype. In the presence of differentiation activators, MLPS/IFNγ secreted high amounts of IL-1β and tumor necrosis factor alpha (TNFα), while M0PMA secreted similar cytokines to MIL-4/IL-13, but low IL-8. After removing the activators and further culture for 3 days in fresh cell culture media, the secretion of IL-6 was found in high concentrations by MIL-4/IL-13, followed by MLPS/IFNγ and MPMA. Interestingly, the secretion of cytokines is enhanced with an increase of fibril density. Through the investigation of macrophage-associated functions during tissue repair, we demonstrated that M1LPS/IFNγ has the potential to enhance monocyte infiltration into tissue, while MIL-4/IL-13 supported fibroblast differentiation into myofibroblasts via transforming growth factor beta 1 (TGF-β1) in dependence of fibril density, suggesting a M2a-like phenotype. Overall, our results suggest that collagen fibril density can modulate macrophage response to favor tissue functions. Understanding of immune response in such complex 3D microenvironments will contribute to the novel therapeutic strategies for improving tissue repair, as well as guidance of the design of immune-modulated materials. Full article
(This article belongs to the Special Issue Extracellular Matrix in Wound Healing)
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Review

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15 pages, 929 KiB  
Review
The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment
by Jun Yang, Gokhan Bahcecioglu and Pinar Zorlutuna
Bioengineering 2020, 7(4), 124; https://doi.org/10.3390/bioengineering7040124 - 11 Oct 2020
Cited by 21 | Viewed by 6226
Abstract
Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in [...] Read more.
Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes. Full article
(This article belongs to the Special Issue Extracellular Matrix in Wound Healing)
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