Treating meniscal lesions remains a major challenge in the preservation of joint health and function. The relevance of addressing meniscal injuries and degeneration is especially important, since meniscectomy remains the preferred surgical approach to date. However, in recent decades, the evolving understanding of meniscal function lead many clinicins towards stategies to prever menisci whenever possible. In fact, the meniscus-deficient knee has been associated with poor outcomes over time, including deterioration of the articular cartilage and compromised stability of the joint, with progression towards a post-meniscectomy osteoarthritis (OA). The MEFISTO project is a European consortium composed of 13 institutions between academic hospitals, universities, and healthcare industry partners that is studying a new, personalized approach, in which a regenerative meniscal scaffold is developed to promote meniscal regeneration in young patient, and a bioactive, non-degradable prosthesis able to modulate joint inflammation is developed for patients with advanced OA. In this presentation, the key 3D printing technologies and approaches to biofunctionalize both the regenerative and non-degradable meniscal analogues that are designed and developed within the consortium will be discussed.
In particular, 3D (bio)printing techniques are rapidly evolving as a powerful tool to capture the anatomical geometries of native tissues, as well as their heterocellular composition, via the spatial patterning of different ECM components, cells and bioactive cues. In the field of meniscus repair, this family of techniques, especially extrusion-based bioprinting can be particularly advantageous to recreate the zonal distribution into a vascular and an avascular zone, as well as the spatially defined integration of key anti- and pro-angiogenic factors to modulate the distribution of ingrowing blood capillaries. The technological innovation promoted by the MEFISTO consortium lies int he development of biologically active functionalized micro- and nanobiomaterials (specificall, including dendrons and drug delivery from polymeric capsules) that can interact with the surrounding articular tissues. In particular, the biodegradable scaffold witll promote the vascularization of the peripheral zone, while leaving th inner zone avascular, relecting the native meniscal tissue. Contextually, the functionalization with drug delivery particles within the surface of the non-degradable device will provide modulation of inflammation. In addition, the ability to print mechanically reinforcing materials, also in the form of microfibrillar polymeric meshes, i.e. via melt electrowriting, can be exploited to endow soft materials such a hydrogels and collagen sponges with mechanical properties analogue to those of native menisci. Finally, new light-based 3D volumetric (bio)printing technologies offer the opportunity to print cell laden structures of anatomically relevant sizes (several centimeters) at an unprecedented velocity, in less than 20 seconds, opening new avenues to facilitate the upscaling of tissue engineered constructs and their translation to meniscal healthcare. Overall, the combination of these 3D bioprinting technologies and the generation of drug loaded scaffolds and regenerative grafts, can offer new opportunities for joint restorative solutions.
This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 814444 (MEFISTO) and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 949806, VOLUME-BIO).