This project aims to apply a cell-based tissue engineering method, known as macromolecular crowding, in order to treat EB in a way that has not been done so before. Through using this method, it is hoped that EB skin will be able to use and produce the missing proteins associated with EB and promote faster wound healing.
Prof. Dimitrios Zevgolis is the Director of the Regenerative, Modular & Developmental Engineering Laboratory (REMODEL) at University College Dublin (UCD), Dublin, Ireland. Through using DEB skin cells in the process of macromolecular crowding, he hopes that the EB skin cells which are not making Collagen 7 will then be encouraged to act like skin cells which have the ability to make Collagen 7. This will in turn heal EB wounds and encourage the cells to make their own Collagen 7 going forward, preventing future wounds from occurring.
Prof Dimitrios Zevgolis is the Director of the Regenerative, Modular & Developmental Engineering Laboratory (REMODEL) at University College Dublin (UCD), Dublin, Ireland. Dimitrios is Irish Ambassador of European Orthopaedic Research Society (EORS); member of the Endorsement and Editorial Committees of Tissue Engineering and Regenerative Medicine International Society (TERMIS); founder and council member of Matrix Biology Ireland (MBI); and Editor-in-Chief of Biomaterials and Biosystems (Elsevier).
He has authored over 100 peer-reviewed articles, over 400 peer-reviewed conference papers and over 15 peer-reviewed book chapters. He is on the editorial board of over 10 journals and acts as reviewer for over 130 journals and 30 funding agencies.
Dimitrios has secured 2 patents and founded 2 companies. He has conducted research for over 40 companies and has been involved in the development and commercialisation of numerous food and medical device products. He now hopes to apply his tissue engineering research expertise in the hopes of finding an effective treatment for DEB.
Epidermolysis Bullosa (EB) is a rare genetic and incurable disease that is associated with severe and painful skin and mucosae fragility, which results in blisters and erosions. It is estimated that 1 per 50,000 live births are diagnosed with EB and that 1 per 100,000 people have the disease. Its severity ranges from mild to fatal and affects every racial and ethnic group worldwide and both sexes equally. The market size of EB in seven (USA, UK, Germany, France, Italy, Spain, Japan) major markets is estimated at US$ 2,283.40 million per year, with compound annual growth rate of 5.67 %. Although cell-based tissue engineering therapies have shown remarkable clinical safety, efficiency and efficacy, no product has been commercialised (they are at various stages of clinical trial assessment).
We have a model of the skin environment in the lab that we want to apply to EB skin. The model is made up of skin cells that are packed really tightly together with other molecules that are found in the skin. The reason for packing the cells and molecules really tightly together is to ensure they behave the same way as when they are packed together in the skin and the molecules can find each other and react the same way they would in the skin. This is called macromolecular crowding. We are going to assess the potential of this model to create functional collagen 7. If it works, it can potentially be applied to DEB wounds to heal them. This type of model makes it faster and cheaper to make commercially because the macromolecular crowding allows for the skin model to develop faster and reduced the manufacturing time compared to other skin models.
If this works for collagen 7 and DEB the same technology can potentially be applied to other types of EB. EB-DOABLE is a collaborative project between the University College Dublin and the University of Alberta.
Epidermolysis bullosa (EB) is a rare genetic and incurable disease that is associated with severe and painful skin and mucosae fragility, which results in blisters and erosions. It is estimated that 1 per 50,000 live births are diagnosed with EB and that 1 per 100,000 people have the disease. Its severity ranges from mild to fatal and affects every racial and ethnic group worldwide and both sexes equally. Although cell-based tissue engineering therapies have shown remarkable clinical safety, efficiency and efficacy, no product has been commercialised (they are at various stages of clinical trial assessment).
Developing lab-grown skin tissues for treating conditions like EB has been slow and costly due to the lengthy time required to grow cells in the lab. Which can also reduce the quality and effectiveness of the cells. To solve this, the team has created a new patented method called macromolecular crowding, which means that in just a few days, skin tissues can be developed as opposed months, all the while maintaining the function of the cells.
In the EB-DOABLE project, researchers assessed how effectively different types of cells produce collagen, a key component of healthy skin. Collagen I, in particular, is the most common protein in the skin and helps rebuild a natural environment for the cells. Researchers found that dermal fibroblasts (human skin cells) were the most efficient at quickly producing collagen I when using their method of macromolecular crowding.
Next, researchers attempted to genetically alter these fibroblasts to make another type of collagen—collagen VII—which is particularly important for individuals with EB. While some progress was made, making the cells produce collagen VII consistently, was more challenging than anticipated. The use of more advanced gene editing techniques will be necessary to fully unlock the benefits of the macromolecular crowding method to treat EB.
Prof Dimitrios Zevgolis
It is our role to increase EB research both in Ireland and across the globe.
We have funded and supported many research initiatives, contributing to a better quality of life for people living with EB.
We work closely alongside researchers, DEBRA International, clinicians and people linked in with us for all our research projects.
