EPFL doctorate Award 2017 – Priscilla Briquez
© 2017 Priscilla Briquez
Therapeutic Proteins Engineered for Super-Affinity to the Extracellular Matrix in Regenerative Medicine, EPFL thesis n°7103 (2016)
Thesis director: Prof. Prof. J. Hubbell
"For elucidating the biomolecular interactions between natural factors that guide tissue repair and the extracellular matrix molecules in tissues, and for using that understanding to design new therapeutics to improve healing of bone and skin."
Upon injury, our body produces some proteins called growth factors, which direct tissue regenerative processes. Despite their promising potential as drugs for applications in wound healing, only few of them reached the clinical market due to limited efficacy, and those that are currently used have been associated with serious side effects (e.g. cancers). The lack of efficacy and safety of growth factors can be attributed to their fast dissipation out of the injured sites. Consequently, the goal of my thesis was to modify these factors to sequester them into the wounds, thus increasing their local efficacy and reducing their side effects.
To do so, we fused the growth factors to a short peptidic domain that displays super-affinity to the extracellular matrix present in our tissues. We successfully demonstrated that our modified growth factors were better retained into the wounds compared to the non-modified “clinical” factors, while fully preserving their bioactivity. Thus, our modified growth factors led to significantly increased regeneration of skin and bone tissue in models of chronic wounds, and to promising results in models of limb ischemia and knee osteoarthritis.
