Microfabrication strategies to produce anisotropic scaffolds for tendon tissue engineering

Tendon injuries are a leading cause of disability in athletes, active working people and elder population worldwide. Partial or total loss of tendon functionality is mainly caused by a poor alignment of collagen fibrils in scar tissue, resulting in significant mechanical limitation of repaired tendons. Since tendon morphology and functionality are intrinsically associated, tendon engineered scaffolds should mimic the anisotropic structural architecture of native tendons to support a complete regeneration of damaged tissues.

Thus, sophisticated scaffolds with aligned structural features were fabricated using micro-fabrication technologies. The microstructures of starch and polycaprolactione (SPCL) matrices created by 3D printing technologies allow to control the spatial distribution of cells and guide cell behavior towards a tenogenic phenotype. Moreover, the integration of magnetic nanoparticles (MNPs) in anisotropic scaffolds to be remotely controlled by an external magnetic field can further contribute for 3D systems with improved functionality and added value for tendon regeneration. Stem cells from adipose tissue laden in smart magnetic scaffolds naturally respond to magnetic forces synthesizing a Tenascin and Collagen I rich matrix. The developed magnetic scaffolds were biocompatible and showed good in vivo integration with surrounding tissues.

Considering that matrix stiffness is also a major stimulus driving cell fate and organization, glycosaminoglycan fiber hydrogels produced by combining microfluidics with polyelectrolyte interactions may be an interesting approach towards the regeneration of tendons. Fiber hydrogels replicate topographical stimulation and elastic properties of tendon, in which tendon derived cells were found to be homogeneously distributed along the fibers, being able to produce the matrix components Collagen I and Tenascin.

Altogether, the developed strategies suggest that magnetic stimulation and biomimetic scaffolds with topographic cues may trigger the next generation of implantable devices for tendon regenerative therapies.