An aligned-to-random PLA/PCL/COL1 bilayer electrospun scaffold loaded with exosomes of bone marrow-derived mesenchymal stem cells promotes tendon-to-bone healing in rats.

The regeneration of tendon-to-bone interface remains a significant clinical challenge due to the highly complex structure, composition, cell population, and mechanical properties of the interface. In this study, polylactic acid (PLA), polycaprolactone (PCL) and type I collagen (Col1) were used as raw materials to prepare a tendon-to-bone interface biomimetic scaffold through electrospinning technology. The nanofiber scaffold features an aligned-to-random bilayer structure mimicking the native ten-don-to-bone interface. Furthermore, when loaded with exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos), the biomimetic scaffold synergistically promotes ten-don-to-bone regeneration. Our results demonstrate that the biomimetic scaffold is biocompatible and promotes cells adhesion, proliferation, and differentiation. In vivo experiments using a rat tendon-to-bone injury model demonstrated that PLA/PCL/COL1&BMSC-Exos scaffold significantly increased fibro-cartilage thickness, improved collagen fiber alignment, and enhanced biomechanical properties, with concurrent improvement in gait performance. The biomimetic scaffold represented a promising therapeutic approach for addressing tendon-to-bone healing and advancing clinical practices in ten-don-to-bone regeneration.