Tunable Smart Biomaterial for Cartilage Regeneration (Ultracart Regenera)

Rheumatoid Arthritis (RA) and Osteoarthritis (OA) are among the most impactful musculoskeletal disorders causing articular cartilage degradation, ultimately leading to loss of the joint functionality. Matrix-assisted Autologous Chondrocytes Implantation (MACI) is one of the most promising reconstructive techniques to treat chondral defects (CDs). MACI relies on a matrix cellularized with autologous chondrocytes implanted directly onto cartilage defects. Despite MACI's effectiveness, post-surgery rehabilitation remains a challenge, as it fails to induce the optimal mechanobiology necessary for an effective cartilage regeneration. Additionally, there is a significant patient-to-patient variability and the local loads occurring during rehabilitation might consequently vary greatly. We propose a personalized approach focused on the delivery local pro-regenerative mechanobiological cues to dramatically improve the cartilage restoration after MACI. We developed an innovative scaffold to be used as matrix in MACI, capable to enhance the cartilage repair by delivering in situ controlled, and personalized, mechanical cues triggering pro-regenerative cellular responses to embedded human articular chondrocytes (hACs). The scaffold relies on an electrospun matrix made of aligned fibers composed of PVDF-TrFE, a piezoelectric polymer, enriched with ferromagnetic Fe 3 O 4 nanoparticles capable to confer magnetic properties to the scaffold. MNPs were simultaneously dispersed in the polymeric solution, and microfibers were collected onto a high-speed rotating collector to obtain an aligned micropattern, capable to give mechanical anisotropy to the scaffold. After cellularization with hACs, we subjected the scaffold to daily magnetic stimulation up to 14 days. The scaffold was highly responsive to external magnetic stimuli. In addition, hACs produced a type II collagen-rich extracellular matrix when cultured within the scaffolds subjected to magnetic stimulation. Remarkably, we observed an increase of cell viability, and of type II/type X collagen ratio. Our scaffold was able to provide pro-regenerative cues to hACs after mechanical cyclic deformations induced by repeated magnetic stimulations. Such an approach paves the way to an effective, and definitive therapeutic procedure for the treatment of chondral defects.