Skin tissue regeneration for burn injury

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Abstract

The skin is the largest organ of the body, which meets the environment most directly. Thus, the skin is vulnerable to various damages, particularly burn injury. Skin wound healing is a serious interaction between cell types, cytokines, mediators, the neurovascular system, and matrix remodeling. Tissue regeneration technology remarkably enhances skin repair via re-epidermalization, epidermal-stromal cell interactions, angiogenesis, and inhabitation of hypertrophic scars and keloids. The success rates of skin healing for burn injuries have significantly increased with the use of various skin substitutes. In this review, we discuss skin replacement with cells, growth factors, scaffolds, or cell-seeded scaffolds for skin tissue reconstruction and also compare the high efficacy and cost-effectiveness of each therapy. We describe the essentials, achievements, and challenges of cell-based therapy in reducing scar formation and improving burn injury treatment.

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Most cited references 174

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p63 identifies keratinocyte stem cells.

G Pellegrini, E Dellambra, O Golisano … (2001)

The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide confined to the stem cells has yet been identified. Here we show that the p63 transcription factor, a p53 homologue essential for regenerative proliferation in epithelial development, distinguishes human keratinocyte stem cells from their TA progeny. Within the cornea, nuclear p63 is expressed by the basal cells of the limbal epithelium, but not by TA cells covering the corneal surface. Human keratinocyte stem and TA cells when isolated in culture give rise to holoclones and paraclones, respectively. We show by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones. TA keratinocytes, immediately after their withdrawal from the stem cell compartment (meroclones), have greatly reduced p63, even though they possess very appreciable proliferative capacity. Clonal evolution (i.e., generation of TA cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3 family of proteins. Keratinocytes whose 14-3-3final sigma has been down-regulated remain in the stem cell compartment and maintain p63 during serial cultivation. The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.

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Biomimetic materials for tissue engineering.

Peter Ma (2008)

Tissue engineering and regenerative medicine is an exciting research area that aims at regenerative alternatives to harvested tissues for transplantation. Biomaterials play a pivotal role as scaffolds to provide three-dimensional templates and synthetic extracellular matrix environments for tissue regeneration. It is often beneficial for the scaffolds to mimic certain advantageous characteristics of the natural extracellular matrix, or developmental or wound healing programs. This article reviews current biomimetic materials approaches in tissue engineering. These include synthesis to achieve certain compositions or properties similar to those of the extracellular matrix, novel processing technologies to achieve structural features mimicking the extracellular matrix on various levels, approaches to emulate cell-extracellular matrix interactions, and biologic delivery strategies to recapitulate a signaling cascade or developmental/wound healing program. The article also provides examples of enhanced cellular/tissue functions and regenerative outcomes, demonstrating the excitement and significance of the biomimetic materials for tissue engineering and regeneration.

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Design and fabrication of human skin by three-dimensional bioprinting.

Vivian W. Lee, Gurtej Singh, John P Trasatti … (2014)

Three-dimensional (3D) bioprinting, a flexible automated on-demand platform for the free-form fabrication of complex living architectures, is a novel approach for the design and engineering of human organs and tissues. Here, we demonstrate the potential of 3D bioprinting for tissue engineering using human skin as a prototypical example. Keratinocytes and fibroblasts were used as constituent cells to represent the epidermis and dermis, and collagen was used to represent the dermal matrix of the skin. Preliminary studies were conducted to optimize printing parameters for maximum cell viability as well as for the optimization of cell densities in the epidermis and dermis to mimic physiologically relevant attributes of human skin. Printed 3D constructs were cultured in submerged media conditions followed by exposure of the epidermal layer to the air-liquid interface to promote maturation and stratification. Histology and immunofluorescence characterization demonstrated that 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue. In comparison with traditional methods for skin engineering, 3D bioprinting offers several advantages in terms of shape- and form retention, flexibility, reproducibility, and high culture throughput. It has a broad range of applications in transdermal and topical formulation discovery, dermal toxicity studies, and in designing autologous grafts for wound healing. The proof-of-concept studies presented here can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases.

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Author and article information

Contributors

Anastasia Shpichka:

ORCID: http://orcid.org/0000-0002-9918-9979

ana-shpichka@yandex.ru

Denis Butnaru: butnaru_dv@mail.ru

Evgeny A. Bezrukov: eabezrukov@rambler.ru

Roman B. Sukhanov: rb_suhanov@mail.ru

Anthony Atala: aatala@wakehealth.edu

Vitaliy Burdukovskii: burdvit@mail.ru

Yuanyuan Zhang: fyyzhang2016@gmail.com

Peter Timashev: timashev.peter@gmail.com

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 15 March 2019

Publication date PMC-release: 15 March 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 94

Affiliations

[1 ]ISNI 0000 0001 2288 8774, GRID grid.448878.f, Institute for Regenerative Medicine, , Sechenov University, ; Moscow, Russia

[2 ]ISNI 0000 0001 2288 8774, GRID grid.448878.f, Sechenov Biomedical Science and Technology Park, , Sechenov University, ; Moscow, Russia

[3 ]ISNI 0000 0001 2288 8774, GRID grid.448878.f, Department of Urology, , Sechenov University, ; Moscow, Russia

[4 ]ISNI 0000 0001 2185 3318, GRID grid.241167.7, Wake Forest Institute for Regenerative Medicine, , Wake Forest School of Medicine, ; Winston-Salem, NC USA

[5 ]ISNI 0000 0004 1765 4596, GRID grid.465428.9, Baikal Institute of Nature Management, Siberian Branch of the Russian Academy of Sciences, ; Ulan-Ude, Russia

[6 ]Research Center “Crystallography and Photonics” RAS, Institute of Photonic Technologies, Troitsk, Moscow, Russia

[7 ]ISNI 0000 0004 0637 9621, GRID grid.424930.8, Departments of Polymers and Composites, , N.N. Semenov Institute of Chemical Physics, ; Moscow, Russia

Author information

Anastasia Shpichka http://orcid.org/0000-0002-9918-9979

Article

Publisher ID: 1203

DOI: 10.1186/s13287-019-1203-3

PMC ID: 6419807

PubMed ID: 30876456

SO-VID: 30ed0352-64ab-4ab4-8b6f-fe15c6b79c86

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100006769, Russian Science Foundation;

Award ID: 18-15-00401

Award Recipient : Peter Timashev

Funded by: Russian academic excellence project 5-100

Award ID: Sechenov University

Award Recipient : Peter Timashev

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: burns,skin regeneration,cell-based therapy,stem cells,skin substitutes

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: burns, skin regeneration, cell-based therapy, stem cells, skin substitutes

Skin tissue regeneration for burn injury

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Universal stem cells

Most cited references 174

p63 identifies keratinocyte stem cells.

Biomimetic materials for tissue engineering.

Design and fabrication of human skin by three-dimensional bioprinting.

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