A 3D-Printed Piezoelectric Scaffold With Bio-Inspired Gradient and Dynamic Adaptation for Tendon Regeneration

Tendon regeneration requires materials that dynamically adapt to the healing stages, offering mechanical support, adhesion prevention, inflammation control, and collagen remodeling. We introduce a novel, dynamically adaptive piezoelectric hydrogel designed to address these requirements. The hydrogel features a bioinspired, anti-adhesive lotus structure to minimize fibroblast and protein adhesion, preventing postoperative complications. Furthermore, it incorporates rationally designed gradients in piezoelectricity, mechanical properties, and degradation rate. These gradients allow the hydrogel to dynamically match the evolving needs of tendon healing, providing adjustable mechanical, electrical stimulation, and controllable degradation. The hydrogel demonstrably reduces inflammation (downregulating TNF-α), promotes M2 macrophage polarization, inhibits bacterial growth, and stimulates endogenous tendon regeneration. This regeneration is characterized by increased collagen I deposition, improved fiber alignment, and enhanced biomechanical properties. Transcriptomic analysis revealed upregulation of genes associated with mechanotransduction, tissue remodeling, and anti-inflammatory responses, alongside downregulation of fibrotic and oxidative stress pathways. This self-powered, multi-gradient scaffold represents a significant advancement in tendon tissue engineering, offering a promising strategy for tendinopathy treatment.