Developing a hydrogel to treat EB wounds using nanoparticles

• Primary Researcher: Prof Nicholas Dunne
• Institution: Dublin City University
• Type of EB: RDEB
• Funding amount: €32,509 with co-funding from the Irish Research Council
• Project Length: 2 years

Due in 2024

Prof Nicholas Dunne is the Chair of Mechanical and Manufacturing Engineering in the School of Mechanical and Manufacturing, the Founding Executive Director of Biodesign Europe and the Executive Director of the Medical Engineering Research Centre Engineering (MedEng) at DCU.

Prior to his appointment at DCU, he was the Professor of Biomaterials Engineering at QUB He has also held Joint-Directorship positions in the Advanced Materials and Processes Research Cluster and the Polymer Processing Research Centre at QUB.

Professor Dunne’s research programme lies at the interface of materials science, engineering and biology. He leads a multidisciplinary group working at the host/biomaterial interface that has played a leading role in the development of biomaterials that simulate an efficacious drug delivery or therapeutic response. This work spans fundamental mechanisms at the host/material interface as well as translational research to target non-union bone defects, bone metastases and chronic wounds. This research has been developed via a strong, interdisciplinary programme complemented with over-arching institutional and industrial collaborations.

Grant Title: A nanoparticle loaded hydrogel for Epidermolysis Bullosa (reGENErate)

Epidermolysis Bullosa (EB) encompasses a group of debilitating medical conditions characterised by fragile skin prone to blistering and peeling due to a weak connection between the dermis (upper layer of the skin) and the epidermis (lower layer of the skin).

In dystrophic EB patients, the primary cause is often a deficiency in the expression of collagen VII, a critical component in connecting the dermis to the epidermis. Currently, the specific treatment of EB faces challenges such as the difficulty of delivering genetic material deep into the skin and poor delivery effectiveness.

The skin’s structure impedes the penetration of larger molecules, making effective delivery a significant obstacle. To address this issue, our proposed solution is to deliver a genetic carrier encoding collagen VII.

Two types of genetic carriers will be compared: (i) mRNA, which offers direct translation to a functional protein, reducing the risk of the gene missing it’s therapeutic target, but requires more frequent administration, and (ii) CRISPR, which can result in long-term overexpression but carries risks associated with genetic editing.

To facilitate cellular uptake of the collagen VII, we will use a peptide carrier called RALA, known for its ability to condense genes into smaller particles, known as nanoparticles. These RALA/Collagen VII nanoparticles will be incorporated into a nanogel system. The nanogel is a smart, polymer-based material that is not toxic and sensitive to changes in the wound environment. It is designed to be waterbiodegradable and will offer a safe and effective means of delivering collagen VII.

By addressing the challenges of delivery effectiveness and effective delivery of genetic material, our innovative approach holds promise for improving the treatment of EB. The development of this nanogel-based system paves the way for a more effective and patient-centred treatment option for individuals suffering from EB.

Due in 2024