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Updated: Oct 27, 2025
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Generation of Self-assembled Vascularized Human Skin Equivalents
Published on: February 12, 2021
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Bio-engineering a prevascularized human tri-layered skin substitute containing a hypodermis.
Jakub Zimoch1, Dominika Zielinska1, Katarzyna Michalak-Micka1
1Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Acta Biomaterialia
|July 24, 2021
Summary
Researchers bioengineered a three-layered skin substitute with epidermis, dermis, and hypodermis from human adipose stem cells. This functional skin graft promotes regeneration and aids in understanding wound healing processes.
Area of Science:
- Regenerative Medicine
- Tissue Engineering
- Dermatology
Background:
- Severe skin injuries necessitate full-thickness skin replacement, including the hypodermis.
- Current skin substitutes often lack a functional hypodermal layer, limiting their regenerative potential.
Purpose of the Study:
- To bioengineer a tri-layered human skin substitute (TLSS) incorporating a functional hypodermis.
- To evaluate the role of the hypodermis in skin substitute development and function.
- To investigate cell-cell interactions influencing epidermal homeostasis and wound healing.
Main Methods:
- Differentiation of human adipose stem cells (ASC) into adipocytes within a collagen type I hydrogel to form the hypodermal layer.
- Integration of the hypodermal layer with a prevascularized dermis (containing endothelial cells and fibroblasts) and an epidermal layer (keratinocytes).
- In vitro and in vivo assessment of hypodermal differentiation, vascularization, and influence on epidermal development using molecular and histological techniques.
Main Results:
- Successful differentiation of ASC into adipocytes confirmed by gene and protein expression (adiponectin, perilipin, FABP-4).
- Demonstrated functional hypodermal characteristics via lipid droplet visualization (Oil Red O, BODIPY, AdipoRed staining).
- Observed that both ASC and adipocytes in the hypodermis positively influenced keratinocyte maturation and epidermal homeostasis, partly via TGF-β1 secretion, impacting epidermal morphogenesis and barrier formation.
Conclusions:
- A novel, functional tri-layered skin substitute (TLSS) with a bioengineered hypodermis and a vascularized dermis was successfully developed.
- The TLSS serves as a valuable model for studying skin regeneration and cell-matrix interactions in wound healing.
- Hypodermal-derived TGF-β1 plays a crucial role in regulating epidermal differentiation and barrier function within the engineered skin construct.
