A reinforced nanofibrous patch with biomimetic mechanical properties and chondroinductive effect for rotator cuff tissue engineering

Patch augmented surgery has been a feasible technique for rotator cuff repair. An ideal rotator cuff tissue engineering patch should have proper mechanical properties to match the native tendons and sufficient biological effect to promote tendon-bone healing. In this study, kartogenin (KGN)-grafted poly (ether-ester-urethane)urea/gelatin composite nanofibrous patches (PEEUU-GEL-KGN) were fabricated via electrospinning process followed by crosslinking of GEL and covalent grafting of KGN. The optimized PEEUU-GEL-KGN nanofibrous patches exhibited biomimetic mechanical properties, including sufficient tensile strength, non-linear stress-strain profiles, and remarkable elasticity and cyclical properties. In vitro investigations revealed that the patches possessed outstanding biocompatibility and performed a sustained release of KGN for a long time. Modification with GEL and KGN significantly improved hydrophilicity of the patches, promoted the adhesion, spreading, and proliferation of mesenchymal stem cells and upregulated the expression of cartilage-related genes. In vivo studies demonstrated that the implanted PEEUU-GEL-KGN patches effectively improved the tissue cellularity and collagen alignment, accelerated the fibrocartilage regeneration, augmented the biomechanical strength of the repaired enthesis, and reinforced the fixing of the tendon to the bone. Overall, the PEEUU-GEL-KGN patches enhanced tendon-bone healing and resisted rotator cuff re-tear. Therefore, the PEEUU-GEL-KGN patch is a highly promising candidate for rotator cuff tissue engineering.