Biodegradable Self-Enhancing Piezoelectric Scaffold for Synchronized Tendon-to-Bone Regeneration

A key challenge in contemporary rotator cuff repair lies in achieving spatiotemporally specific differentiation of stem cells within the intricate tendon-bone interface (TBI) microenvironment, thereby enabling the synchronous regeneration of functionally graded tendon, fibrocartilage, and bone tissues. Existing scaffold designs often fail to adequately replicate the mechanical gradients and biochemical heterogeneity of the natural TBI microenvironment, particularly in reconstructing the precise spatial organization of the tendon-cartilage-bone transitional zone. This study innovatively integrates the in situ electrical stimulation advantages of piezoelectric degradable scaffolds, the topological guidance mediated by electrospun fibers, and biomimetic mineralization capabilities to construct a "mechanical-electrical-biochemical cue" coupled system for structural reconstruction and functional restoration of TBI. The gradient scaffold, designed with structural-component matching, generates a piezoelectric enhancement effect during stress concentration, creating precise electrical stimulation and mechanical microenvironment gradients within the fiber scaffold. This enhanced electrical signal is three times greater than the piezoelectric performance of traditional poly(l-lactic acid) scaffolds. This dynamically controllable electrical signal activates the PI3K/AKT signaling pathway, modulating mesenchymal stem cells differentiation toward tenogenic, chondrogenic, and osteogenic lineages. In a rat rotator cuff tear (RCT) model, this gradient-structured, fully biodegradable scaffold combined with electrical stimulation therapy was demonstrated to achieve coordinated multi-tissue regeneration in complex TBI.