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Cited by 104Wound Healing and TreatmentsDermatologic Treatments and ResearchTissue Engineering and Regenerative Medicine

The DOI matches its Crossref record; 168 of the 168 references it cites were found in a registry or an index.

Human In Vitro Skin Models for Wound Healing and Wound Healing Disorders

Open access
Hofmann, Elisabeth, Fink, Julia, Pignet, Anna-Lisa, Schwarz, Anna, Schellnegger, Marlies, Nischwitz, Sebastian P., Holzer-Geissler, Judith C. J., Kamolz, Lars-Peter, Kotzbeck, Petra·2023·Biomedicines
DOI 10.3390/biomedicines11041056PMC PMC10135654
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Abstract

Skin wound healing is essential to health and survival. Consequently, high amounts of research effort have been put into investigating the cellular and molecular components involved in the wound healing process. The use of animal experiments has contributed greatly to the knowledge of wound healing, skin diseases, and the exploration of treatment options. However, in addition to ethical concerns, anatomical and physiological inter-species differences often influence the translatability of animal-based studies. Human in vitro skin models, which include essential cellular and structural components for wound healing analyses, would improve the translatability of results and reduce animal experiments during the preclinical evaluation of novel therapy approaches. In this review, we summarize in vitro approaches, which are used to study wound healing as well as wound healing-pathologies such as chronic wounds, keloids, and hypertrophic scars in a human setting.

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Crossref · 10.3390/biomedicines11041056

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Figures

Figure 1 A schematic overview of the 2D and 3D in vitro models of the human skin. (A) Different cell types can be isolated from human skin samples. Epidermal keratinocytes are extracted from the epidermal part and fibroblasts from the dermal part of the skin. (B) Fibroblasts and keratinocytes are cultivated separately in a 2D monolayer. (C) Transwell co-culture systems comprise fibroblasts, which are grown on the well bottom, and keratinocytes, which are cultivated in a porous insert. This allows the exchange of soluble factors without direct contact between different cell types. (D) In the reconstructed human epidermis (RHE) model, stratified keratinocytes are cultured in a porous membrane at the air–liquid interface on top of a collagen matrix. (E) In a human skin equivalent (HSE), keratinocytes are cultivated atop a dermal equivalent composed of fibroblasts embedded in an ECM-like matrix [26].
Figure 1 A schematic overview of the 2D and 3D in vitro models of the human skin. (A) Different cell types can be isolated from human skin samples. Epidermal keratinocytes are extracted from the epidermal part and fibroblasts from the dermal part of the skin. (B) Fibroblasts and keratinocytes are cultivated separately in a 2D monolayer. (C) Transwell co-culture systems comprise fibroblasts, which are grown on the well bottom, and keratinocytes, which are cultivated in a porous insert. This allows the exchange of soluble factors without direct contact between different cell types. (D) In the reconstructed human epidermis (RHE) model, stratified keratinocytes are cultured in a porous membrane at the air–liquid interface on top of a collagen matrix. (E) In a human skin equivalent (HSE), keratinocytes are cultivated atop a dermal equivalent composed of fibroblasts embedded in an ECM-like matrix [26].CC BY · PubMed Central
Figure 2 Ideal in vitro models of wound healing disorders envisioned to reproduce clinical key aspects. (A) Chronic wounds are characterized by an impaired repair process. A prolonged inflammatory phase, hypoperfusion/ischemia, infections, and/or biofilm formation keep chronic wounds from transcending to the proliferation phase [55,56]. (B) Keloids are enlarged, raised, tumor-like scars that can even extend beyond the original margins of a wound. Keloid tissue is composed of disorganized, thick, eosinophilic collagen type I and III bundles that are randomly oriented [1]. (C) Hypertrophic scars have a red/pink color as well as an elevated and uneven surface. In contrast to keloids, they do not extend beyond the margins of the primary wound. Hypertrophic scars are characterized by the persistence of myofibroblasts, which contribute to enhanced contraction, and increased production of collagen and a-SMA [1,78,79].
Figure 2 Ideal in vitro models of wound healing disorders envisioned to reproduce clinical key aspects. (A) Chronic wounds are characterized by an impaired repair process. A prolonged inflammatory phase, hypoperfusion/ischemia, infections, and/or biofilm formation keep chronic wounds from transcending to the proliferation phase [55,56]. (B) Keloids are enlarged, raised, tumor-like scars that can even extend beyond the original margins of a wound. Keloid tissue is composed of disorganized, thick, eosinophilic collagen type I and III bundles that are randomly oriented [1]. (C) Hypertrophic scars have a red/pink color as well as an elevated and uneven surface. In contrast to keloids, they do not extend beyond the margins of the primary wound. Hypertrophic scars are characterized by the persistence of myofibroblasts, which contribute to enhanced contraction, and increased production of collagen and a-SMA [1,78,79].CC BY · PubMed Central

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Metadata

Authors
Hofmann, E., Fink, J., Pignet, A.-L., Schwarz, A., Schellnegger, M., Nischwitz, S. P., Holzer-Geissler, J. C. J., Kamolz, L.-P., & Kotzbeck, P.
Affiliations
  • Joanneum Research (AT)
  • Medical University of Graz (AT)
Corresponding author
Kotzbeck, Petra
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-03-30
Volume
11
Issue
4
Pages
1056
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines11041056
PMC
PMC10135654
OpenAlex
W4361273951
Cited by
104
References
168
Citations by year
2026: 33 · 2025: 36 · 2024: 28 · 2023: 7
FWCI
3.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Austrian Federal Ministry of Climate Action, Environment, Energy, Mobility, Innovation and Technology (BMVIT-612.018/0016-lll/I1/2018-Tec.Reg, BurnSkin 888162)
  • Austrian Research Promotion Agency (BMVIT-612.018/0016-lll/I1/2018-Tec.Reg, BurnSkin 888162)
Topics
  • Health Sciences › Medicine › Surgery › Wound Healing and Treatments
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
wound healing, chronic wounds, keloids, hypertrophic scars, wound healing disorders, translational research, reduction of animal experiments

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