A transformative innovation in the study of skin diseases

Dominican Republic – Mayo Clinic has developed its first three-dimensional bioprinted human skin prototype to model inflammatory skin diseases. Three-dimensional bioprinting is a technology that combines bioinks with living cells to print structures similar to natural tissues in three dimensions. This new technology provides the most human-like skin model to study inflammatory conditions such as atopic dermatitis, commonly known as eczema, a chronic inflammatory skin condition that causes dry, itchy, and Causes inflamed skin. The three-dimensional skin bioprinting process, its applications and limitations are described in a review article published in the journal Regenerative Biomaterials.

«Three-dimensional bioprinting is an emerging field in tissue engineering and regenerative medicine that has the potential to transform clinical and laboratory practice. In this article, we discuss the process of 3D skin bioprinting, including cell selection, support matrix selection, and the advantages and disadvantages of some skin bioinks,” explains Dr. Saranya Wiles, dermatologist and lead author of the article. “This three-dimensional model recreates the disease more accurately, creating surgical grafts and offering the possibility of testing new treatments.”

A disease with few variants that causes dryness and itching

A disease with few variants that causes dryness and itching

Eczema is a painful condition that causes dry, itchy skin, which can trigger an immune response and cause inflammation in the skin. Eczema can weaken the skin’s ability to retain moisture and protect itself from bacterial, viral or fungal infections. People suffering from this disease are often at risk for conditions like asthma and food allergies. The few treatments that exist may relieve symptoms, but they are not a cure.

Research to better understand eczema and develop new treatments for the condition is limited due to the lack of preclinical models that accurately simulate the human disease.

«This is where three-dimensional bioprinting offers new options. “This could create human counterparts that are more faithful and representative of the disease, as opposed to the animal models we have worked with in the past,” says Dr. Voyles. “Models of inflammatory skin diseases and rare diseases can be obtained (using bioprinting) to better understand the underlying pathology and study drugs and how they may affect the patient.”

Dr. Voyles’ team, which also includes fellow scientist Dr. Alexander Revzin, hopes to reproduce the inflammatory skin condition to bioprint three-dimensional skin using cells from people with eczema. The research team will analyze topical and injectable regenerative therapies, such as exosome technology, on bioprinted skin in hopes of identifying new treatments. Exosomes are cell-free substances that act as a delivery service that carries cargo from one cell to another, carrying instructions for targeting to the precise tissues that need repair.

Dr. Voyles’ research is supported by the Mayo Clinic Center for Regenerative Biotherapies and funded by the Skoll Foundation. Their work contributes to the center’s goal of offering new cellular treatments for complex conditions with few therapeutic options.

Bioprinting a complex organ

The skin is the largest organ of the body and regenerates every month. Three-dimensional bioprinting models aim to reproduce the complexity of skin layers, but do not yet include the sweat glands, blood vessels, skin follicles and nerves found in native human tissue.

Three-dimensional bioprinting model aims to reproduce complexity of skin layers

«The three-dimensional bioprinter uses human cells as ink called bioinks, which work similarly to ink in printer cartridges. “We can print skin from cells from patients with atopic dermatitis or eczema,” says Dr. Voyles. “Our system allows us to use six different types of cells to model and recreate human skin tissue.”

The research team used several types of cells, such as melanocytes, which make skin color; keratinocytes, which allow skin renewal; and fibroblasts, which form connective tissue. These cells are printed in layers that stratify and mature into entire layers of skin.

“The printing process is like coating a tiered cake with different types of cells,” explains Dr. Voyles. “You start at the bottom (dermis), then you add the next layer (epidermis) and the support matrix material acts as a covering to connect the layers. The printed skin is placed in an incubator where cells can communicate with each other, expand, and form the bioprinted skin.

Research using three-dimensional bioprinted skin is not limited to inflammatory diseases. Dr. Voyles also uses prototyping three-dimensional modeling to better understand at the molecular level the role of senescent cells in age-related skin conditions. Also called zombie cells, senescent cells no longer divide or multiply, so they cannot heal and repair tissues. Dr.’s goal is to better develop new treatments against skin aging.

More research is needed to bioprint an exact replica of human skin suffering from atopic dermatitis. Future studies will explore full-thickness three-dimensional bioprinting of skin with an emphasis on capturing all patient-specific skin characteristics.

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