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Vascularized skin models to reduce animal use in dermatology

Vascularized skin models to reduce animal use in dermatology

Mikolaj Bogdan Ogrodnik (ORCID: 0000-0003-3137-2037)
  • Grant DOI 10.55776/P35382
  • Funding program Principal Investigator Projects
  • Status ended
  • Start April 1, 2022
  • End June 30, 2024
  • Funding amount € 297,933

Disciplines

Biology (20%); Clinical Medicine (30%); Medical Biotechnology (50%)

Keywords

    Cellular Senescence, Skin, Bioengineering, Burn Wounds, Dermatology, Aging

Abstract Final report

Understanding the biological phenomena behind a skin`s response to injury is crucial to developing new treatments. In dermatology, the branch of medicine focused on the skin, research on wound healing and skin aging are of great interest. The skin is an exceptionally complex tissue. Therefore, dermatology research relies heavily on studying the skin of laboratory animals, which brings with it significant ethical concerns. In addition, animal models have scientific drawbacks, such as biological differences between human skin and the skin of animals used in research, such as mice and rats. One solution to help reduce animal usage and focus on human anatomy is replacing animal models with artificial skin generated in the laboratory, so-called in vitro models made up of cells. Some simple artificial skin models already exist and are, for example, used to test the safety of cosmetic products. These models consist of a cell sheets similar to the epidermis, the outermost layer of the skin. However, such a single sheet of cells is missing many essential parts of normal skin: for example, it is not as thick and lacks blood vessels. Thus, due to their simplicity, artificial skin models cannot answer most research questions of the field of dermatology. In response to these issues, this project aims to develop a new, more complex and realistic artificial skin model designed to replicate the anatomy of human skin better than the currently available models. The model we plan to develop has an advantage over the currently used cell sheets: it will be thicker and include blood vessels. Rather than one sheet of cells, it will be made up of several sheets of cells. Underneath the top layer of epidermis, it will include cells found in the underlying layer called the dermis. The dermis itself consists of the connective tissue to make skin pliable, and blood vessels to deliver nutrients to all layers of the skin. As a result, the artificial skin we intend to generate can be supplied with nutrients through the embedded blood vessels. This type of nutrient delivery makes this new artificial model much more similar to the skin on the human body. We will establish a reliable protocol to create these advanced skin-like models. Afterwards, we will perform experiments to show if the complex structure behaves similarly to human skin and can be used instead of the skin of research animals. In particular, we intend to use this artificial skin to study injury and healing processes, in particular by seeing how skin responds to burns and how these burn wounds heal. The results gained during this project will help understand how skin cells react to burn injury and which therapeutic interventions can help to accelerate the healing process.

Understanding the biological phenomena behind a skin's response to injury is crucial to developing new treatments. In dermatology, the branch of medicine focused on the skin, research on wound healing and skin aging are of great interest. The skin is an exceptionally complex tissue. Therefore, dermatology research relies heavily on studying the skin of laboratory animals, which brings with it significant ethical concerns. In addition, animal models have scientific drawbacks, such as biological differences between human skin and the skin of animals used in research, such as mice and rats. One solution to help reduce animal usage and focus on human anatomy is replacing animal models with artificial skin generated in the laboratory, so-called in vitro models made up of cells. Some simple artificial skin models already exist and are, for example, used to test the safety of cosmetic products. These models consist of a cell sheets similar to the epidermis, the outermost layer of the skin. However, such a single sheet of cells is missing many essential parts of normal skin: for example, it is not as thick and lacks blood vessels. Thus, due to their simplicity, artificial skin models cannot answer most research questions of the field of dermatology. In response to these issues, this project aimed to develop a new, more complex and realistic artificial skin model designed to replicate the anatomy of human skin better than the currently available models. The model has an advantage over the currently used cell sheets: it will be thicker and include blood vessels. Rather than one sheet of cells, it is made up of several sheets of cells. Underneath the top layer of epidermis, it includes cells found in the underlying layer called the dermis. The dermis itself consists of the connective tissue to make skin pliable, and blood vessels to deliver nutrients to all layers of the skin. As a result, the artificial skin we generated is supplied with nutrients through the embedded blood vessels. This type of nutrient delivery makes this new artificial model much more similar to the skin on the human body. We established a novel method by combining novel techniques to cultivate cells with advanced 3D-printing. As the next step, we aim to perform experiments to show if the complex structure behaves similarly to human skin and can be used instead of the skin of research animals. In particular, we intend to use this artificial skin to study skin injuries and skin pathologies.

Research institution(s)
  • Ludwig Boltzmann Gesellschaft - 21%
  • Ludwig Boltzmann Gesellschaft - 79%
Project participants
  • Johannes Grillari, Ludwig Boltzmann Gesellschaft , associated research partner

Research Output

  • 43 Citations
  • 5 Publications
  • 6 Scientific Awards
Publications
  • 2025
    Title Cells of all trades - on the importance of spatial positioning of senescent cells in development, healing and aging.
    DOI 10.1002/1873-3468.70037
    Type Journal Article
    Author Dworak H
    Journal FEBS letters
    Pages 2087-2106
  • 2024
    Title In the land of not-unhappiness: On the state-of-the-art of targeting aging and age-related diseases by biomedical research.
    DOI 10.1016/j.mad.2024.111929
    Type Journal Article
    Author Klinaki E
    Journal Mechanisms of ageing and development
    Pages 111929
  • 2023
    Title The p-rpS6-zone delineates wounding responses and the healing process.
    DOI 10.1016/j.devcel.2023.04.001
    Type Journal Article
    Author Dworak H
    Journal Developmental cell
  • 2023
    Title The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations.
    DOI 10.1038/s43587-023-00447-5
    Type Journal Article
    Author Gladyshev Vn
    Journal Nature aging
    Pages 766-775
  • 2022
    Title The role of senescence in cellular plasticity: Lessons from regeneration and development and implications for age-related diseases
    DOI 10.1016/j.devcel.2022.04.005
    Type Journal Article
    Author Ring N
    Journal Developmental Cell
    Pages 1083-1101
    Link Publication
Scientific Awards
  • 2024
    Title Keynote lecture at the EWMA meeting 2024
    Type Personally asked as a key note speaker to a conference
    Level of Recognition Continental/International
  • 2023
    Title Keynote lecture at the Meeting of Polish Society for Animal Physiology
    Type Personally asked as a key note speaker to a conference
    Level of Recognition National (any country)
  • 2023
    Title Keynote lecture at the TERMIS EU (Manchester, UK)
    Type Personally asked as a key note speaker to a conference
    Level of Recognition Continental/International
  • 2023
    Title Best Abstract Award at LBG Innovation in Health Sciences Meeting 2023
    Type Poster/abstract prize
    Level of Recognition National (any country)
  • 2023
    Title Best Young Investigator Award at the Annual meeting of the Austrian Cluster for Tissue Regeneration 2023
    Type Poster/abstract prize
    Level of Recognition Regional (any country)
  • 2022
    Title Keynote lecture at the TERMIS AP (Jeju, South Korea)
    Type Personally asked as a key note speaker to a conference
    Level of Recognition Continental/International

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