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Tissue-Engineered Skin Substitutes: The State-of-the-Art and Future Perspectives
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Tissue-Engineered Skin Substitutes: The State-of-the-Art and Future Perspectives

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

Deadline for manuscript submissions: closed (20 May 2024) | Viewed by 6058

Special Issue Editor

Dr. Agnes Klar

E-Mail Website
Guest Editor
Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, 8032 Zurich, Switzerland
Interests: human skin; keratinocytes; endothelial cells; skin substitutes; stem cells; melanocytes; adipose-dervied stem cells; fat tissue; skin inflammation; immune cells; skin adipocyte progenitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The skin is responsible for several important physiological functions and has enormous clinical significance in wound healing. Recently, tissue engineering emerged as a new strategy to create improved pigmented and prevascularized skin substitutes for both in vitro testing and clinical applications. Tissue-engineered substitutes offer an alternative for patients suffering from skin injuries to support regeneration of the epidermis, dermis, or both. Our Special Issue highlights some of the latest approaches to skin regeneration and biofabrication using tissue engineering techniques. Those new developments offer strategies to fabricate multilayered skin allowing rapid bench to bedside translation.

This Special Issue focuses on recent biomedical advances, ranging from cellular-level therapies such as mesenchymal stem cell or growth factor delivery, to large-scale biofabrication techniques including 3D printing to recapitulate the biological, architectural, and functional complexity of native skin.

Dr. Agnes Klar
Guest Editor

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Keywords

  • tissue-engineered skin
  • skin tissue scaffolds
  • skin substitutes
  • vascularization
  • pigmentation
  • wound healing
  • 3D printing
  • full-thickness wounds
  • clinical perspectives
  • skin regeneration
  • scar-free skin healing
  • immuno-inflammation, hypertrophic scars
  • keloids macrophages

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Published Papers (3 papers)

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Research

14 pages, 5451 KiB  
Article
Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo
by Martin A. Barbier, Karel Ferland, Henri De Koninck, Emilie J. Doucet, Ludivine Dubourget, MinJoon Kim, Bettina Cattier, Amélie Morissette, Mbarka Bchetnia, Danielle Larouche, Dong Hyun Kim, Guillaume St-Jean and Lucie Germain
Int. J. Mol. Sci. 2024, 25(3), 1513; https://doi.org/10.3390/ijms25031513 - 26 Jan 2024
Viewed by 1396
Abstract
Tumorigenic assays are used during a clinical translation to detect the transformation potential of cell-based therapies. One of these in vivo assays is based on the separate injection of each cell type to be used in the clinical trial. However, the injection method [...] Read more.
Tumorigenic assays are used during a clinical translation to detect the transformation potential of cell-based therapies. One of these in vivo assays is based on the separate injection of each cell type to be used in the clinical trial. However, the injection method requires many animals and several months to obtain useful results. In previous studies, we showed the potential of tissue-engineered skin substitutes (TESs) as a model for normal skin in which cancer cells can be included in vitro. Herein, we showed a new method to study tumorigenicity, using cancer spheroids that were embedded in TESs (cTES) and grafted onto athymic mice, and compared it with the commonly used cell injection assay. Tumors developed in both models, cancer cell injection and cTES grafting, but metastases were not detected at the time of sacrifice. Interestingly, the rate of tumor development was faster in cTESs than with the injection method. In conclusion, grafting TESs is a sensitive method to detect tumor cell growth with and could be developed as an alternative test for tumorigenicity. Full article
(This article belongs to the Special Issue Tissue-Engineered Skin Substitutes: The State-of-the-Art and Future Perspectives)
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22 pages, 3618 KiB  
Article
Effects of an Adipose Mesenchymal Stem Cell-Derived Conditioned medium and TGF-β1 on Human Keratinocytes In Vitro
by Hyrije Ademi, Katarzyna Michalak-Micka, Ueli Moehrlen, Thomas Biedermann and Agnes S. Klar
Int. J. Mol. Sci. 2023, 24(19), 14726; https://doi.org/10.3390/ijms241914726 - 29 Sep 2023
Cited by 3 | Viewed by 2009
Abstract
Human keratinocytes play a crucial role during skin wound healing and in skin replacement therapies. The secretome of adipose-derived stem cells (ASCs) has been shown to secrete pro-healing factors, among which include TGF-β1, which is essential for keratinocyte migration and the re-epithelialization of [...] Read more.
Human keratinocytes play a crucial role during skin wound healing and in skin replacement therapies. The secretome of adipose-derived stem cells (ASCs) has been shown to secrete pro-healing factors, among which include TGF-β1, which is essential for keratinocyte migration and the re-epithelialization of cutaneous wounds during skin wound healing. The benefits of an ASC conditioned medium (ASC-CM) are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in keratinocytes. Here, we evaluated the composition and the innate characteristics of the ASC secretome and its biological effects on keratinocyte maturation and wound healing in vitro. In particular, we detected high levels of different growth factors, such as HGF, FGFb, and VEGF, and other factors, such as TIMP1 and 4, IL8, PAI-1, uPA, and IGFBP-3, in the ASC-CM. Further, we investigated, using immunofluorescence and flow cytometry, the distinct effects of a human ASC-CM and/or synthetic TGF-β1 on human keratinocyte proliferation, migration, and cell apoptosis suppression. We demonstrated that the ASC-CM increased keratinocyte proliferation as compared to TGF-β1 treatment. Further, we found that the ASC-CM exerted cell cycle progression in keratinocytes via regulating the phases G1, S, and G2/M. In particular, cells subjected to the ASC-CM demonstrated increased DNA synthesis (S phase) compared to the TGF-β1-treated KCs, which showed a pronounced G0/G1 phase. Furthermore, both the ASC-CM and TGF-β1 conditions resulted in a decreased expression of the late differentiation marker CK10 in human keratinocytes in vitro, whereas both treatments enhanced transglutaminase 3 and loricrin expression. Interestingly, the ASC-CM promoted significantly increased numbers of keratinocytes expressing epidermal basal keratinocyte markers, such DLL1 and Jagged2 Notch ligands, whereas those ligands were significantly decreased in TGF-β1-treated keratinocytes. In conclusion, our findings suggest that the ASC-CM is a potent stimulator of human keratinocyte proliferation in vitro, particularly supporting basal keratinocytes, which are crucial for a successful skin coverage after transplantation. In contrast, TGF-β1 treatment decreased keratinocyte proliferation and specifically increased the expression of differentiation markers in vitro. Full article
(This article belongs to the Special Issue Tissue-Engineered Skin Substitutes: The State-of-the-Art and Future Perspectives)
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14 pages, 3526 KiB  
Article
The Synergistic Effect of Electrical Stimulation and Dermal Fibroblast Cells-Laden 3D Conductive Hydrogel for Full-Thickness Wound Healing
by Yen-Hong Lin, En-Wei Liu, Yun-Jhen Lin, Hooi Yee Ng, Jian-Jr Lee and Tuan-Ti Hsu
Int. J. Mol. Sci. 2023, 24(14), 11698; https://doi.org/10.3390/ijms241411698 - 20 Jul 2023
Cited by 3 | Viewed by 1899
Abstract
Clinically, most patients with poor wound healing suffer from generalized skin damage, usually accompanied by other complications, so developing therapeutic strategies for difficult wound healing has remained extremely challenging until now. Current studies have indicated that electrical stimulation (ES) to cutaneous lesions enhances [...] Read more.
Clinically, most patients with poor wound healing suffer from generalized skin damage, usually accompanied by other complications, so developing therapeutic strategies for difficult wound healing has remained extremely challenging until now. Current studies have indicated that electrical stimulation (ES) to cutaneous lesions enhances skin regeneration by activating intracellular signaling cascades and secreting skin regeneration-related cytokine. In this study, we designed different concentrations of graphene in gelatin-methacrylate (GelMa) to form the conductive composite commonly used in wound healing because of its efficiency compared to other conductive thermo-elastic materials. The results demonstrated the successful addition of graphene to GelMa while retaining the original physicochemical properties of the GelMa bioink. In addition, the incorporation of graphene increased the interactions between these two biomaterials, leading to an increase in mechanical properties, improvement in the swelling ratio, and the regulation of degradation characteristics of the biocomposite scaffolds. Moreover, the scaffolds exhibited excellent electrical conductivity, increasing proliferation and wound healing-related growth factor secretion from human dermal fibroblasts. Overall, the HDF-laden 3D electroconductive GelMa/graphene-based hydrogels developed in this study are ideal biomaterials for skin regeneration applications in the future. Full article
(This article belongs to the Special Issue Tissue-Engineered Skin Substitutes: The State-of-the-Art and Future Perspectives)
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