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Biotechnological Approaches and Biomaterials for Wound Healing: From Scarring to Tissue Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 19362

Special Issue Editor


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Guest Editor
1. Department of Chemistry, Faraday Building, Lancaster University, Lancaster LA1 4YB, UK
2. Materials Science Institute, Faraday Building, Lancaster University, Lancaster LA1 4YB, UK
Interests: polymer synthesis; supramolecular materials; biomaterials; stimuli-responsive materials; drug delivery; tissue engineering; sustainability
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Special Issue Information

Dear Colleagues,

There are various wound types encountered on humans and animals on a daily basis (e.g., abrasions, acute wounds, burn wounds, contusions, lacerations, surgical wounds/incision, and traumatic wounds). The healing process can be delayed by a number of factors, both local (related to the wound itself) and systemic (related to the patient and their clinical condition), which has potential for significant cost for the healthcare system and society. Despite the clinical need for improved wound healing outcomes, there is little innovation in wound healing technologies on the market.

This Special Issue is devoted to state-of-the-art biotechnological approaches and biomaterials for wound healing. Such biotechnological approaches include materials and methods that enhance wound healing (including therapeutic, diagnostic, and clinical procedures) in organs and tissues.

We warmly welcome the submission of manuscripts on the topic of the “Biotechnological Approaches and Biomaterials for Wound Healing: From Scarring to Tissue Regeneration” Special Issue.

Dr. John G. Hardy
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • antimicrobial
  • bioactivity
  • bioengineering
  • bioethics
  • biomaterials
  • biophysical approaches
  • biosensors
  • biotechnology
  • chemosensors
  • drug delivery
  • imaging
  • regenerative medicine
  • scar tissue
  • stem cells

Published Papers (5 papers)

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Research

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16 pages, 3779 KiB  
Article
3D Bioprinting of Gelatin–Xanthan Gum Composite Hydrogels for Growth of Human Skin Cells
by Beatrice Piola, Maurizio Sabbatini, Sarah Gino, Marco Invernizzi and Filippo Renò
Int. J. Mol. Sci. 2022, 23(1), 539; https://doi.org/10.3390/ijms23010539 - 4 Jan 2022
Cited by 24 | Viewed by 4501
Abstract
In recent years, bioprinting has attracted much attention as a potential tool for generating complex 3D biological constructs capable of mimicking the native tissue microenvironment and promoting physiologically relevant cell–cell and cell–matrix interactions. The aim of the present study was to develop a [...] Read more.
In recent years, bioprinting has attracted much attention as a potential tool for generating complex 3D biological constructs capable of mimicking the native tissue microenvironment and promoting physiologically relevant cell–cell and cell–matrix interactions. The aim of the present study was to develop a crosslinked 3D printable hydrogel based on biocompatible natural polymers, gelatin and xanthan gum at different percentages to be used both as a scaffold for cell growth and as a wound dressing. The CellInk Inkredible 3D printer was used for the 3D printing of hydrogels, and a glutaraldehyde solution was tested for the crosslinking process. We were able to obtain two kinds of printable hydrogels with different porosity, swelling and degradation time. Subsequently, the printed hydrogels were characterized from the point of view of biocompatibility. Our results showed that gelatin/xanthan-gum bioprinted hydrogels were biocompatible materials, as they allowed both human keratinocyte and fibroblast in vitro growth for 14 days. These two bioprintable hydrogels could be also used as a helpful dressing material. Full article
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21 pages, 7489 KiB  
Article
Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing
by Barbara Gawronska-Kozak, Katarzyna Walendzik, Sylwia Machcinska, Artur Padzik, Marta Kopcewicz and Joanna Wiśniewska
Int. J. Mol. Sci. 2022, 23(1), 257; https://doi.org/10.3390/ijms23010257 - 27 Dec 2021
Cited by 7 | Viewed by 2831
Abstract
Dermal white adipose tissue (dWAT) is involved in the maintenance of skin homeostasis. However, the studies concerning its molecular regulation are limited. In the present paper, we ask whether the introduction of two transcription factors, Foxn1 and Hif-1α, into the post-wounded skin of [...] Read more.
Dermal white adipose tissue (dWAT) is involved in the maintenance of skin homeostasis. However, the studies concerning its molecular regulation are limited. In the present paper, we ask whether the introduction of two transcription factors, Foxn1 and Hif-1α, into the post-wounded skin of Foxn1−/− mice regulates dWAT during wound healing (days 3 and 6). We have chosen lentivirus vectors (LVs) as a tool to deliver Foxn1 and Hif-1α into the post-wounded skin. We documented that combinations of both transgenes reduces the number, size and diameter of dermal adipocytes at the wound bed area. The qRT-PCR analysis of pro-adipogenic genes, revealed that LV-Hif-1α alone, or combined with LV-Foxn1, increases the mRNA expression of Pparγ, Glut 4 and Fasn at post-wounding day 6. However, the most spectacular stimulatory effect of Foxn1 and/or Hif-1α was observed for Igf2, the growth factor participating in adipogenic signal transduction. Our data also shows that Foxn1/Hif-1α, at post-wounding day 3, reduces levels of CD68 and MIP-1γ mRNA expression and the percentage of CD68 positive cells in the wound site. In conclusion, the present data are the first to document that Foxn1 and Hif-1α cooperatively (1) regulate dWAT during the proliferative phase of skin wound healing through the Igf2 signaling pathway, and (2) reduce the macrophages content in the wound site. Full article
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9 pages, 2197 KiB  
Article
LncRNA MALAT1 Modulates TGF-β1-Induced EMT in Keratinocyte
by Liping Zhang, Junyi Hu, Bahar I. Meshkat, Kenneth W. Liechty and Junwang Xu
Int. J. Mol. Sci. 2021, 22(21), 11816; https://doi.org/10.3390/ijms222111816 - 30 Oct 2021
Cited by 17 | Viewed by 2816
Abstract
One of the major complications in diabetes is impaired wound healing. Unfortunately, effective therapies are currently lacking. Epithelial to mesenchymal transition (EMT) is a critical process involved in cutaneous wound healing. In response to injury, EMT is required to activate and mobilize stationary [...] Read more.
One of the major complications in diabetes is impaired wound healing. Unfortunately, effective therapies are currently lacking. Epithelial to mesenchymal transition (EMT) is a critical process involved in cutaneous wound healing. In response to injury, EMT is required to activate and mobilize stationary keratinocytes in the skin toward the wound bed, which allows for re-epithelialization. This process is stalled in diabetic wounds. In this study, we investigate the role of long non-coding RNA (lncRNA), MALAT1, in transforming growth factor beta 1(TGF-β1)-induced EMT of human keratinocyte (HaCaT) cells. Initially, we detected MALAT1 and TGF-β1 expression in non-diabetic and diabetic wounds and found that these expression are significantly up-regulated in diabetic wounds. Then, HaCaT cells were cultured and exposed to TGF-β1. The EMT of HaCaT cells were confirmed by the increased expression of CDH2, KRT10, and ACTA2, in addition to the down-regulation of CDH1. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 silencing attenuates TGFβ1-induced EMT. Mechanistically, MALAT1 is involved in TGF-β1 mediated EMT through significantly induced ZEB1 expression, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in TGFβ1-induced EMT of human HaCaT cells and provides new understanding for the pathogenesis of diabetic wounds. Full article
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Review

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30 pages, 1893 KiB  
Review
Advances in Immunomodulation and Immune Engineering Approaches to Improve Healing of Extremity Wounds
by Preeti J. Muire, Marc A. Thompson, Robert J. Christy and Shanmugasundaram Natesan
Int. J. Mol. Sci. 2022, 23(8), 4074; https://doi.org/10.3390/ijms23084074 - 7 Apr 2022
Cited by 7 | Viewed by 3213
Abstract
Delayed healing of traumatic wounds often stems from a dysregulated immune response initiated or exacerbated by existing comorbidities, multiple tissue injury or wound contamination. Over decades, approaches towards alleviating wound inflammation have been centered on interventions capable of a collective dampening of various [...] Read more.
Delayed healing of traumatic wounds often stems from a dysregulated immune response initiated or exacerbated by existing comorbidities, multiple tissue injury or wound contamination. Over decades, approaches towards alleviating wound inflammation have been centered on interventions capable of a collective dampening of various inflammatory factors and/or cells. However, a progressive understanding of immune physiology has rendered deeper knowledge on the dynamic interplay of secreted factors and effector cells following an acute injury. There is a wide body of literature, both in vitro and in vivo, abstracted on the immunomodulatory approaches to control inflammation. Recently, targeted modulation of the immune response via biotechnological approaches and biomaterials has gained attention as a means to restore the pro-healing phenotype and promote tissue regeneration. In order to fully realize the potential of these approaches in traumatic wounds, a critical and nuanced understanding of the relationships between immune dysregulation and healing outcomes is needed. This review provides an insight on paradigm shift towards interventional approaches to control exacerbated immune response following a traumatic injury from an agonistic to a targeted path. We address such a need by (1) providing a targeted discussion of the wound healing processes to assist in the identification of novel therapeutic targets and (2) highlighting emerging technologies and interventions that utilize an immunoengineering-based approach. In addition, we have underscored the importance of immune engineering as an emerging tool to provide precision medicine as an option to modulate acute immune response following a traumatic injury. Finally, an overview is provided on how an intervention can follow through a successful clinical application and regulatory pathway following laboratory and animal model evaluation. Full article
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25 pages, 4429 KiB  
Review
Cellular Interaction of Human Skin Cells towards Natural Bioink via 3D-Bioprinting Technologies for Chronic Wound: A Comprehensive Review
by Syafira Masri, Mazlan Zawani, Izzat Zulkiflee, Atiqah Salleh, Nur Izzah Md Fadilah, Manira Maarof, Adzim Poh Yuen Wen, Fatih Duman, Yasuhiko Tabata, Izhar Abd Aziz, Ruszymah Bt Hj Idrus and Mh Busra Fauzi
Int. J. Mol. Sci. 2022, 23(1), 476; https://doi.org/10.3390/ijms23010476 - 1 Jan 2022
Cited by 25 | Viewed by 4858
Abstract
Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to [...] Read more.
Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine. Full article
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