Ultrasound-Triggered Tendon-Bone Comb With Axially Graded Electrical Gradients for Tendon-Bone Interface Integration

Loss of electrophysiological guidance from endogenous fibrous-channeled electrical conduction critically impairs repair of the injured tendon-bone interface (TBI). Clinical analysis indicates that the inconsistent efficacy of conventional electrostimulation (ES) therapy arises from the limited penetration depth and insufficient focusing capacity of electrical currents in biological tissues. In this study, we developed a tendon-bone comb, termed the gradient microneedle (GMN), to improve spatial precision of electrical-signal delivery through multiple independent channel units and thereby promote targeted TBI regeneration. Ultrasonic acoustic radiation force was used to guide the graded distribution of piezoelectric nanoparticles within the GMN. In vitro, under ultrasonic stimulation (1 W), the GMN generated a gradient electric field that closely matched the optimal intensity required to direct the biphasic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo studies demonstrated that the GMN increased host bone integration by 101% compared with control systems and promoted functional recovery in rat and porcine TBI injury models. Additionally, GMN-mediated acoustic-electrical stimulation promoted graded regeneration of the complex by triggering Ca^{2 +} influx and subsequently regulating the FoxO and JAK1-STAT3 signaling pathways. Overall, this study presents a GMN that reconstructs physiological bioelectrical gradients and enhances osteointegration, offering a novel gradient ES strategy for regenerating interfacial tissues.