In the pursuit for engineering CELL HYBRIDGE regenerative medicine implants able to regenerate skeletal tissues by controlling adult stem cell activity, we have developed an innovative method to successfully improve cell migration into nanofibrillar scaffolds. In addition to having a direct impact in CELL HYBRIDGE as part of the planned activities aimed at increasing cell migration into the engineered skeletal implants, we unexpectedly discovered that the same scaffolds display wavy patterns similar to how collagen fibers in several tissues in our body are organized. Even more intriguing, these wavy patterns had a direct influence on cell differentiation by enhancing their intrinsic capacity to produce growth factors.
Driven by these observations, we have optimized the methodology and are able today to control the formation of such wavy patterns at a single fiber as well as multiple fiber scales by controlling the degree of buckling that the fibers are exposed to during processing. In doing so, we focused on reproducing the same waviness that is observed in tendons and ligaments. Therefore, the aim of BUCKLING BRIDGES was to further investigate these instructive scaffolds as potentially smart implants for the regeneration of tendons and ligaments. To focus our efforts, we specifically took the case of the anterior cruciate ligament (ACL), which is one of the most recurring ligament prone to injury due to sport activities across different age-spans in our society.
In the course of the project, we have further standardized the production of wavy scaffolds with aligned fibers mimicking more specifically the orientation and organization of collagen fibers the ACL. The fabricated scaffolds were tested in vitro and in vivo. The scaffolds provided with the opportunity to increase cellular infiltration over 1 cm thickness, and increase 2x the secretion of endogenous growth factors and of the mechanical properties (stiffness; yield strain and stress; presence of toe region as in native tendons and ligaments) compared to non-wavy scaffolds. Furthermore, the scaffolds showed to support and maintain in time ligament tissue formation in vitro. This also resulted in robust tissue regeneration in vivo, despite in some cases we observed rupture of the implants to a similar degree compared to what reported with other commercially available products in the market.
While doing so, we also started to explore the market potential of such products and develop a first synthetic draft of a business plan for the creation of a spin-off company, which we called TISSUE BRICKS.
