A Dual Therapeutic Approach for Tendon Regeneration: Combining Three-Dimensional (3D) Printing, Three-Dimensional (3D) Bioprinting, and Gene Engineering

Tendon injuries pose a considerable challenge due to their limited regenerative capacity and the inadequacy of current therapeutic approaches. This study explores an innovative dual-component scaffold designed to replicate the native tendon microenvironment and promote tissue regeneration. The system integrates a hydrogel core composed of alginate, nanocellulose, gelatine, and hyaluronic acid, encapsulating genetically engineered D1 murine mesenchymal stem cells (D1-MSCs). These cells were transfected with a non-viral plasmid vector to overexpress transforming growth factor-beta 3 (TGF-β3), a key driver of tenogenic differentiation. Surrounding the hydrogel is a synthetic mesh made of polycaprolactone (PCL) or PCL reinforced with graphene oxide (GO), offering structural integrity and enhanced bioactivity. The hydrogel exhibited optimal rheological properties, including high shear-thinning behaviour, rapid viscosity recovery, and a favourable balance of structural integrity and extrusion uniformity, ensuring excellent printability. Cell viability remained high within the scaffolds post-fabrication, confirming their biocompatibility. Furthermore, the transfected D1-MSCs demonstrated significant upregulation of tenogenic markers, including SCX and Col3a1. The incorporation of GO into the synthetic mesh further augmented the scaffold’s mechanical properties. This dual-component system showcases the synergistic potential of bioengineered hydrogels, nanomaterials, and advanced genetic engineering techniques for tendon regeneration. By combining tailored rheological properties, effective cell differentiation, and scaffold bioactivity, this approach offers a promising pathway toward the development of translational solutions for tendon injuries