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.

Highlights

  • Atopic dermatitis (AD), psoriasis, and melanoma are among the skin diseases with the highest global disability-adjusted life years (DALYs) [1]

  • This review focuses on the progress made towards accurately modeling skin diseases using 3D human skin equivalents (HSEs) over the last decade and the development of different methods for producing these models

  • Initial investigation comparing 3D HSEs containing induced pluripotent stem cells (iPSCs)-derived keratinocytes and fibroblasts to 3D HSEs containing normal healthy keratinocytes (NHKs) and normal healthy fibroblasts (NHFs) has shown the potential for iPSC-derived keratinocytes and fibroblasts in future 3D HSEs [61]

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Summary

Introduction

Most skin disease models use a basic form of HSE generated using manual deposition of an epidermal compartment composed of keratinocytes and cell media over a dermal compartment composed of fibroblasts and collagen type I [12,13,14,15]. While these models do provide more insight into the pathogenesis of skin disease than a typical 2D in vitro model would, they fail to fully capture the intricacies of both healthy and diseased skin. Particular emphasis is placed on the use of 3D bioprinting in construction of

Overview of Skin Structure and Function
Skin Diseases
Current 3D Bioengineered Models of Skin Disease
Epidermolysis Bullosa Models
Ichthyosis Models
Atopic Dermatitis Models
Psoriasis Models
Scleroderma Models
Melanoma Models
Methods for Generating 3D Human Skin Equivalents
Challenges in Engineering 3D Skin Models
Current Advances in the Field of Skin Engineering
Findings
Future Directions

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