Biofabrication of Human Skin with Its Appendages

Abstract

Much effort has been made to generate human skin organ in the laboratory. Yet, the current models are limited due to the lack of many critical biological and structural features of the skin. Importantly, these in vitro models lack appendages and fail to recapitulate the whole human skin construction. Thus, engineering a human skin with the capacity to generate all components, including appendages, is a major challenge. This review intends to provide an update on the recent efforts underway to regenerate appendage-bearing skin organs based on scaffold-free and scaffold-based bioengineering approaches. Although the mouse skin equivalents containing hair follicles, sebaceous glands, and sweat glands have been established in vitro, there has been limited success in humans. A combination of biofabricated matrices and cell aggregates, such as organoids, can pave the way for generating skin substitutes with human-like biological, structural, and physical features. Accordingly, the formation of human skin organoids and reconstruction of vascularized skin equipped with immune cells prompt calls for more scientific research. The generation of appendage-bearing skin substitutes can be applied in practice for wound healing, hair restoration, and scar treatment.

Full Skin Equivalent Models for Simulation of Burn Wound Healing, Exploring Skin Regeneration and Cytokine Response

“…The next step in the development of in vitro skin models will be the integration of immune cells, blood vessels, or other relevant skin appendages [ 50 , 51 , 52 , 53 ] and developing models suitable for drug discovery and testing [ 54 ]. Cells from different (disease-related) origins, such as skin cells derived from fetal, burn, or scar tissue, could be used to study their effect on skin regeneration.…”

Development of Physiologically Relevant Skin Organoids from Human Induced Pluripotent Stem Cells

“…Thus, current studies aim to develop approaches to generate touch-responsive skin with pigmented cells. [16] Bright-field imaging confirmed the development of pigmented hiSKOs at day 120 using the optimized protocols (Figure 6A). The presence of melanocytes in the SKOs organoids was further validated by immunostaining and H&E staining (Figure 6B,C; representative images from P111 cell line).…”

“…Thus, current studies aim to develop approaches to generate touch‐responsive skin with pigmented cells. [ 16 ]…”

“…[ 6b,19 ] Upon wounding, especially those affecting deeper layers of the dermis or hypodermis, many elements of this complexity are lost and a simple barrier with limited mechanical properties is produced, the scar, which has a poor sensibility and does not contain any of the skin appendages. [ 16 ] SKOs represent a new hope to produce skin in its full integrity. In this study, we developed an optimized protocol for generating SKOs from hiPSCs, expanding the applicability of generating SKOs to more hiPSCs lines.…”

An optimized protocol for generating appendage-bearing skin organoids from human-induced pluripotent stem cells

“…Existing methods of generating human skin in vitro have, until very recently, been limited in their ability to recapitulate the functional organ [ 2 ]. Bilayer skin equivalent models, for example, succeed in recapitulating the stratified squamous epithelium of the epidermis and the underlying fibroblasts of the dermis, but due to the simplistic co-culture approach, fail to generate any skin appendages (i.e.…”