The MECHANO FIBROSIS project culminated with significant insights into the mechanobiology of fibrosis. The project's results, both in vitro and in vivo, have been critical in unraveling the complex cellular responses in fibrotic environments.
During its outgoing phase, the project developed an in vitro model revealing the regulatory coupling of force and focal adhesion kinase (FAK) signaling at focal adhesions (FAs). This breakthrough demonstrated the linear relationship between traction force and FAK phosphorylation at individual FAs in fibrotic/stiff environments. These findings were crucial in understanding the coordinated cellular responses to external forces, such as cell migration and tissue-scale force coordination, critical in tissue stiffness and fibrosis progression. Finally, an in vivo model further illuminated how cell adhesive forces regulate immune cell function during tissue repair processes. Impaired tissue revascularization and aberrant immune cell migration are hallmarks of tissue fibrosis progression. By using the dorsal skinfold window chamber model and intravital imaging, we assessed the impact of cell adhesive forces on immune cell migration and tissue revascularization, underscoring the complexity of fibrotic tissue dynamics.
In the final phase, the project optimized a disease model that more accurately replicates the fibrotic environment. The novel molecular tools and biosensors developed enabled a deeper understanding of the cellular mechanotransduction mechanisms involved in fibrotic disease progression.
Exploitation, and Dissemination:
The project's achievements were widely disseminated through high-impact journals(i.e. Nat Comm, Advanced materials and Science Advances), international conferences (Society for Biomaterials (SFB), European Society for Biomaterials (ESB) and GRC Fibronectin, integrins and other related molecules), and biomaterials workshops (INM, Germany and NCSU, USA), ensuring knowledge transfer within the scientific community to extend the international network of the MECHANO FIBROSIS project. Particularly, in the final phase the integration of FRET biosensor technology and cell engineering techniques in collaborating labs at the host institution underscores the project's significant impact on the broader research field.
Finally, the findings have opened avenues for novel therapeutic strategies targeting mechanotransduction pathways in fibrotic diseases. The developed tools can be incorporated into a biomaterial (hydrogel) offering unique properties and potential for use as anti-fibrotic therapeutic device or diagnostic tools.
In conclusion, the MECHANO FIBROSIS project not only achieved its scientific objectives but also laid down a foundation for future therapeutic developments and opened new horizons in the field of mechanobiology and tissue engineering
