Innovative Electrospun Scaffolds for Tendon Regeneration: A Novel Approach to Prevent Post-Surgical Fibrosis

Tendons are dense connective tissues composed of an extracellular matrix predominantly made of collagen I fibers, providing stability, and mechanical resistance to the joints. Sadly, tendons face a limited self-healing capacity due to low vascularity and cellularity, making tendon ruptures (TRs) a clinical challenge since surgical repair often results in fibrotic tissue with reduced mechanical resistance. Our work aims to address this issue adopting a combined approach relying on tissue engineering and drug delivery to mitigate post-surgery tendon fibrosis. Our strategy exploits a 3D electrospun scaffold with tendon-like microarchitecture, cellularized with human tenocytes (hTCs), and loaded with Rolipram as antifibrotic agent to avoid tendon fibrosis after surgical repair. In our study, we used PLA to produce aligned microfibers that mimic the natural arrangement of collagen fibers in native tendons. We provided microfibers with a type I collagen coating to modulate the drug delivery kinetics, and to induce a self-assembling of microfibers into fascicle-like substructures. These substructures were preserved in 3D scaffolds fabricated with a homemade bundle-making device, which assembles microfibers into a helicoidal quaternary structure. The collagen coating significantly increased the Young's modulus of drug-free (from 102.93 to 140.09 MPa) and drug-loaded (from 103.3 to 144.23 MPa) scaffolds. Conversely, the Rolipram loading did not affect the mechanical behavior, as shown by the comparable Young's modulus of PLA (102.93 MPa) and PLA/Rol (103.3 MPa) samples. Beside mechanical properties, the coating also modulated the kinetic release of Rolipram loaded within the scaffolds microfibers. Specifically, we didn't notice any burst release neither from uncoated (PLA/Rol) nor from coated (PLA/Rol/Coll) scaffolds within first 2h. We obtained compelling result also from biological characterization of our tendon-like scaffolds. Histomorphological analysis via H&E revealed hTCs in both inner and outer scaffold regions. This effect was enhanced in collagen-coated scaffolds that showed a more intense staining. Our study shows encouraging results, demonstrating the potential of our methodology in regenerating non-fibrotic tendons after surgical repair. We acknowledge the support of COST Action TENET.