Tissue Engineering of Human Skin Equivalents

Tissue engineering of human skin equivalents seeks to recreate the structural, functional and immunological properties of native skin in vitro. Constructs typically comprise an epidermal layer of keratinocytes atop a dermal compartment populated by fibroblasts within a biomaterial scaffold. Advanced models may incorporate a hypodermal component, vascular networks and immune cells to mimic in vivo physiology. Scaffolds range from natural polymers such as collagen, fibrin and hyaluronic acid to synthetic hydrogels and composite materials, chosen to support cell adhesion, proliferation and extracellular matrix deposition. Fabrication techniques include manual layering, bioprinting and microfabrication, enabling precise spatial control of cell–matrix organisation. Skin equivalents serve diverse applications in wound healing research, drug and cosmetic testing, disease modelling and grafting for burn and chronic-wound patients. By reducing reliance on animal models and improving preclinical predictivity, these technologies address ethical and translational challenges. Ongoing efforts focus on integrating immune competence, vascular perfusion and appendage formation, with an emphasis on standardisation, reproducibility and scalability for clinical translation.

Research from Nature Portfolio

Recent work has demonstrated that the choice of culture medium critically influences the viability and functional responses of co-cultured keratinocytes, fibroblasts and macrophages in three-dimensional skin equivalents. Studies evaluating mixed differentiation media reveal that standard epidermal or macrophage formulations compromise either skin maturation or immune cell activity. Tailored media conditions have been identified that support robust keratinocyte stratification while preserving macrophage morphology and cytokine responsiveness. These findings underscore the necessity of optimised immunocompetent co-culture systems for physiologically relevant skin models.

Tissue Engineering of Human Skin Equivalents publication trend

The graph below shows the total number of articles in tissue engineering of human skin equivalents across all publications each year (not limited to Nature Index journals).

Technical terms

Scaffold: A three-dimensional biomaterial framework that supports cell attachment, growth and matrix deposition.

Keratinocyte: The primary epithelial cell of the skin’s outer layer responsible for barrier formation.

Fibroblast: A mesenchymal cell in the dermis that synthesises extracellular matrix proteins.

Extracellular matrix (ECM): A network of proteins and glycosaminoglycans providing structural support and biochemical cues to cells.

Hydrogel: A hydrated polymer network used as a cell-friendly scaffold with tunable mechanical properties.

Bioprinting: The additive manufacturing of tissue constructs by layer-by-layer deposition of cells and biomaterials.

References

1. Targeted Antibacterial Endolysin to Treat Infected Wounds on 3D Full-Thickness Skin Model: XZ.700 Efficacy. Pharmaceutics (2024).
2. In vitro skin culture media influence the viability and inflammatory response of primary macrophages. Scientific Reports (2021).
3. Modelling the Complexity of Human Skin In Vitro. Biomedicines (2023).
4. Evaluation of native and non‐native biomaterials for engineering human skin tissue. Bioengineering & Translational Medicine (2022).