Surpassing expectations via joint innovation

Developing the next generation hydrogel using Pepscan’s RGD bicyclic peptides

Pepscan and 13 other partners participated in the Horizon 2020 – Marie Skodowska-Curie project BIOGEL’s consortium. “Our primary task was to fabricate cell-specific bicyclic peptides that can be utilized to modify the hydrogels with specific integrin-binding domains, in this case RGD, to direct cells,” says Peter Timmerman, CSO at Pepscan. Paul Kouwer, Assistant Professor at Radboud University, adds: “Our preliminary results show a thousand-fold increase in cell binding. You can only imagine how this will accelerate our studies!”

Hydrogels are a critical part of various biomedical applications, like research on coatings, tumor cell behavior, tissue engineering and regenerative medicine and diagnostics. Following the end of the project, BIOGEL Coordinator Laura De Laporte (Professor at DWI – Leibniz Institute for Interactive Materials and the RWTH University Aachen) and consortium members Paul Kouwer and Peter Timmerman reflect on the project and its results.

State-of-the-art biologically active and responsive hydrogels
Hydrogels are soft, water-rich, polymeric networks that are increasingly utilized in advanced materials for biomedicine. However, clinical application of these fascinating materials has been staying behind due to the lack of temporal and spatially controlled chemical, biological and physical properties. “The aim of BIOGEL was to come up with innovative solutions to overcome current limitations in the molecular and material design of hydrogels and render them more functional, for example with more selective and stronger peptides to interact with cells,” says De Laporte.

“What we were looking for were new strategies to control the interactions between the cells and their environment. Pepscan designed highly specific peptides that allows us to engineer exactly that interaction,” says Kouwer. “Additionally, highly designed and purified peptides also address the challenges associated with source, contamination and immunogenicity that exist for naturally derived biological matrices.”

Thousand-fold improvement
“We built a novel biofunctionalization platform based on preliminary data obtained with simple peptides. The next step was to incorporate a novel type of bicyclic (called 2-CLIPS) specific peptide with a well-defined 3D spatial structure, resembling the native functional protein surface. In the hydrogel, these RGD peptides served as ligands for the cell’s membrane receptors,” says Timmerman. Two publications related to this topic appeared in the ACS Combinatorial Sciences Journal:

• Bicyclic RGD Peptides with Exquisite Selectivity for the Integrin αvβ3 Receptor Using a “Random Design” Approach
• High-Affinity α5β1-Integrin-Selective Bicyclic RGD Peptides Identified via Screening of Designed Random Libraries

Kouwer’s research group has been studying hydrogels decorated with the bicyclic peptides from Pepscan as next level synthetic regenerative matrices. “The improved –better than Nature– binding between cell and the matrix drives cell response into a higher gear. As a result, the experimental timeframe of a typical cell culture experiment has decreased significantly. Where we normally need a week to conduct a study, we are now able to do this within a 12-hour time frame. You can only imagine how this will accelerate our studies.” A paper focusing on the final results of this study will be published in a renowned journal in the upcoming period.

Collaboration boosts innovation
The collaboration on the Horizon 2020 – Marie Skodowska-Curie project BIOGEL’s consortium is facilitating innovation. De Laporte: “Education was an integral element of this project. In total, 14 PhD-students were part of the consortium, resulting in a solid basis of next generation scientists active in the hydrogel field, spurring future innovation.” Dominik Bernhagen, who worked at Pepscan for this project, recently received his doctorate. “The fact that almost all the other project members were present at this event shows the positive energy and strong connection amongst the scientists participating in this project,” says Timmerman.

Kouwer concludes: “The various interdisciplinary and cultural backgrounds of those in our team has helped the BIOGEL project gain valuable new insights into hydrogels and will lead to significant innovations to the biomedical field.”