Cited by 223D Printing in Biomedical ResearchSkin and Cellular Biology ResearchTissue Engineering and Regenerative Medicine

Bioengineered Efficacy Models of Skin Disease: Advances in the Last 10 Years

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Stanton, Diana Nicole, Ganguli-Indra, Gitali, Indra, Arup Kumar, Karande, Pankaj·2022·Pharmaceutics

Abstract

Models of skin diseases, such as psoriasis and scleroderma, must accurately recapitulate the complex microenvironment of human skin to provide an efficacious platform for investigation of skin diseases. Skin disease research has been shifting from less complex and less relevant 2D (two-dimensional) models to significantly more relevant 3D (three-dimensional) models. Three-dimensional modeling systems are better able to recapitulate the complex cell–cell and cell–matrix interactions that occur in vivo within skin. Three-dimensional human skin equivalents (HSEs) have emerged as an advantageous tool for the study of skin disease in vitro. These 3D HSEs can be highly complex, containing both epidermal and dermal compartments with integrated adnexal structures. The addition of adnexal structures to 3D HSEs has allowed researchers to gain more insight into the complex pathology of various hereditary and acquired skin diseases. One method of constructing 3D HSEs, 3D bioprinting, has emerged as a versatile and useful tool for generating highly complex HSEs. The development of commercially available 3D bioprinters has allowed researchers to create highly reproducible 3D HSEs with precise integration of multiple adnexal structures. While the field of bioengineered models for study of skin disease has made tremendous progress in the last decade, there are still significant efforts necessary to create truly biomimetic skin disease models. In future studies utilizing 3D HSEs, emphasis must be placed on integrating all adnexal structures relevant to the skin disease under investigation. Thorough investigation of the intricate pathology of skin diseases and the development of effective treatments requires use of highly efficacious models of skin diseases.

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  • aHSEs can integrate additional cell types including endothelial cells, melanocytes, neuronal cells, lymphatic cells, immune cells, adipocytes, pluripotent stem cells, and skin appendages.

    “These include endothelial cells to vascularize the dermis [46] and melanocytes to introduce pigmentation [47]. Furthermore, neuronal cells [48,49], lymphatic cells [50], immune cells (e.g. dermal dendritic cells [51], monocytes [52], T cells [53], and macrophages [54]), adipocytes and adipose tissue [49,55,56], pluripotent stem cells [22,36,57], and skin appendages such as hair follicles or sweat”

    From Diversity of human skin three-dimensional organotypic cultures (2024) · cites this paper as [18]

    Section 7 (page unavailable) describes HSEs incorporating endothelial and lymphatic endothelial cells, neural components, immune cells, adipocytes, pluripotent stem cells, and skin appendages. The copy identifies melanocytes as pigment-producing cells in natural skin (Section 2), but the passages found do not establish their integration into HSEs; they also do not establish monocytes as a separately incorporated cell type. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • HSEs are used to investigate wound healing, aging, and various diseases.

    “HSEs are used to investigate various aspects of normal and abnormal skin biology, including wound healing [40,41], aging [42,43], and the study of various diseases [18].”
  • The expansion of aHSEs enhances the application of OTC models for investigating therapeutic techniques, particularly in mimicking inflammatory skin diseases like psoriasis and atopic dermatitis, and in studying skin-related bacterial adhesion and infection.

    “This expansion enhances the application of OTC models for investigating potential therapeutic techniques [18,60], particularly in mimicking inflammatory skin diseases like psoriasis and atopic dermatitis [59], while also studying skin-related bacterial adhesion and infection [22,45].”

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Cited by

Sorted by citations

Authors
Stanton, D. N., Ganguli-Indra, G., Indra, A. K., & Karande, P.
Affiliations
  • Rensselaer Polytechnic Institute (US)
  • Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA
  • Oregon State University (US)
Corresponding author
Karande, Pankaj
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2022-01-28
Volume
14
Issue
2
Pages
319
ISSN
1999-4923 (ISSN-L)
OpenAlex
W4214693541
Cited by
22
References
3
Citations by year
2026: 8 · 2025: 6 · 2024: 6 · 2022: 2
FWCI
0.31
Type
journal article
Language
en
Open access
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of General Medical Sciences (T32GM141865)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
human skin equivalents, 3D bioprinting, adnexal structures, psoriasis, systemic sclerosis, cell-matrix interactions

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