Electrohydrodynamic‐Printed Dual‐Triphase Microfibrous Scaffolds Reshaping the Lipidomic Profile for Enthesis Healing in a Rat Rotator Cuff Repair Model

Abstract

Rotator cuff injuries often result in chronic pain and functional limitations due to retears and scar formation at the enthesis. This study assess the efficacy of electrohydrodynamic‐printed microfibrous dual‐triphase scaffolds (DTSs), designed to optimize enthesis repair. These scaffolds, composed of polycaprolactone enhanced with nanohydroxyapatite, nano‐magnesium‐oxide, and kartogenin demonstrate significant biological advantages. In vitro, the scaffolds support over 95% stem cell viability and promote enhanced expression of critical markers such as tenomodulin (TNMD), sex‐determining region Y‐Box transcription factor 9 (SOX‐9), and runt‐related transcription factor 2 (RUNX‐2). Enhanced expressions of tendon markers tenomodulin and scleraxis (SCX) are noted, alongside significant upregulation of chondrocyte and osteoblast markers. In vivo, these scaffolds significantly improve the biomechanical properties of the repaired enthesis, with a maximum failure load of 27.0 ± 4.2 N and ultimate stress of 5.5 ± 1.0 MPa at 6 weeks postimplantation. Lipidomic analysis indicates substantial regulation of phospholipids such as phosphatidylcholine and phosphatidylserine, highlighting the scaffold's capacity to modulate biochemical pathways critical for tissue repair and regeneration. This study underscores the potential of DTS to improve clinical outcomes in rotator cuff injury treatment by enhancing cellular differentiation, biomechanical properties, and biochemical environment, setting a foundation for personalized treatment strategies in tendon–bone repair.