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Cited by 17Advancements in Transdermal Drug Delivery3D Printing in Biomedical ResearchWound Healing and Treatments

Skin models of cutaneous toxicity, transdermal transport and wound repair

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Vilela de Sousa, Inês, Ferreira, Miguel J S, Bebiano, Luís B, Simões, Sandra, Matos, Ana Filipa, Pereira, Rúben F, Granja, Pedro L·2023·Burns & Trauma
DOI 10.1093/burnst/tkad014PMC PMC10382248
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Abstract

Abstract Skin is widely used as a drug delivery route due to its easy access and the possibility of using relatively painless methods for the administration of bioactive molecules. However, the barrier properties of the skin, along with its multilayer structure, impose severe restrictions on drug transport and bioavailability. Thus, bioengineered models aimed at emulating the skin have been developed not only for optimizing the transdermal transport of different drugs and testing the safety and toxicity of substances but also for understanding the biological processes behind skin wounds. Even though in vivo research is often preferred to study biological processes involving the skin, in vitro and ex vivo strategies have been gaining increasing relevance in recent years. Indeed, there is a noticeably increasing adoption of in vitro and ex vivo methods by internationally accepted guidelines. Furthermore, microfluidic organ-on-a-chip devices are nowadays emerging as valuable tools for functional and behavioural skin emulation. Challenges in miniaturization, automation and reliability still need to be addressed in order to create skin models that can predict skin behaviour in a robust, high-throughput manner, while being compliant with regulatory issues, standards and guidelines. In this review, skin models for transdermal transport, wound repair and cutaneous toxicity will be discussed with a focus on high-throughput strategies. Novel microfluidic strategies driven by advancements in microfabrication technologies will also be revised as a way to improve the efficiency of existing models, both in terms of complexity and throughput.

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  • Reconstructed skin equivalents and organoid models lack integrated vascular and immune-associated compartments, limiting their capacity to model dynamic inflammatory processes.

    “Although reconstructed skin equivalents and organoid models have advanced our understanding of epidermal differentiation, they lack integrated vascular and immune-associated compartments, limiting their capacity to model dynamic inflammatory processes 38,39 .”

    From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [38]

    The Review’s “Microfluidic strategies for skin emulation” section reports that adding microvasculature to a skin-on-a-chip enabled cytokine production and leukocyte infiltration, supporting the importance of vascular and immune-related features for modelling inflammation. It does not establish that reconstructed skin equivalents and organoid models generally lack both compartments or that this specifically limits all such models. Page numbers were not available in our copy. (LLM, conf=0.80)

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Cited by

Sorted by citations

Authors
Vilela de Sousa, I., Ferreira, M. J. S., Bebiano, L. B., Simões, S., Matos, A. F., Pereira, R. F., & Granja, P. L.
Affiliations
  • i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Rua Dr. Manuel Pereira da Silva, 4200-393 Porto , Portugal
  • Universidade do Porto (PT)
  • University of Lisbon (PT)
Corresponding author
Granja, Pedro L
ORCID
Venue
Burns & Trauma
Publisher
Oxford University Press (OUP)
Published
2023-01-01
Volume
11
Pages
tkad014-tkad014
ISSN
  • 2321-3868 (ISSN-L)
  • 2321-3876
DOI
10.1093/burnst/tkad014
PMC
PMC10382248
OpenAlex
W4385339570
Cited by
17
References
10
Citations by year
2026: 7 · 2025: 4 · 2024: 4 · 2023: 2
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Burns & Trauma (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Foundation for Science and Technology (UID/BIM/04293/2020, PTDC/BBB-BIO/1889/2014, UID/DTP/04138/2020, UIDB/DTP/04138/2020)
  • Engineering and Physical Sciences Research Council
  • Medical Research Council (EP/L014904/1)
  • Henry Royce Institute for Advanced Materials (EP/R00661X/1, EP/P025021/1, EP/P025498/1)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
skin model, skin toxicity, transdermal drug transport, wound healing, in vitro skin model, ex vivo skin model, organ-on-a-chip, microfluidics, microfabrication, high-throughput screening, skin barrier, drug bioavailability

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