Functionalized 3D-Printed PEI scaffolds synergize immunomodulation and cartilage regeneration to accelerate tendon–bone healing

The tendon–bone interface is a specialized transitional structure featuring a four-layered gradient organization—tendon, unmineralized fibrocartilage, mineralized fibrocartilage, and bone—that enables smooth mechanical load transfer between soft and hard tissues. Its intrinsic regenerative capacity is extremely limited, and post-injury repair is often replaced by mechanically inferior scar tissue, increasing the risk of re-injury. Conventional tissue engineering scaffolds have largely focused on structural mimicry but frequently neglect modulation of the local immune microenvironment, particularly macrophage-mediated chronic inflammation, which hinders fibrocartilaginous layer regeneration and functional integration. Here, we developed a 3D-printed multifunctional polyetherimide (PEI)-based scaffold capable of simultaneously releasing bioactive Silicate (Si), calcium (Ca), and zinc (Zn) ions(P-CaSiO 3 -ZnO). The scaffold exhibits suitable mechanical strength, interconnected porosity, and controlled ion release. In vitro, it promoted osteogenic, chondrogenic, and tenogenic differentiation while modulating inflammatory responses. In vivo experiments, P-CaSiO 3 -ZnO scaffold accelerated new bone formation, organized collagen deposition, and fibrocartilaginous layer regeneration, achieving robust tendon–bone interface integration and markedly improved mechanical performance. These findings demonstrate a promising strategy for functional tendon–bone interface repair by integrating multi-tissue regeneration and immunomodulatory capabilities. • Sequentially regulated ion release synchronizes stage-specific biological functions with the dynamic healing process. • Beyond structural mimicry, our scaffold suppresses fibrotic scarring by immunomodulating inflammation via Zn²⁺ release. • Integrating 3D printing with hybrid design and surface coatings bridges the gap between mechanical strength and biological complexity.