Biomimetic Wavy-Crimped Porous Structure Enhances Tendon Attachment Reconstruction via Integrin-FAK/Src-MAPK Signaling Axis.

Abstract

Large bone defects often necessitate suturing tendons to the surfaces of porous prostheses to restore joint function. However, current porous structures frequently trigger fibrotic healing at the tendon-prosthesis interface, leading to disorganized tissue and insufficient mechanical strength, which critically limits long-term stability and recovery. In native tendons, collagen fibers exhibit a wavy-crimped microstructure that guides tendon-derived stem cells (TDSCs) alignment and promotes tenogenic differentiation. Inspired by this architecture, we developed a biomimetic tendon wavy-crimped porous titanium scaffold (BT). In a rabbit patellar tendon attachment reconstruction model, BT scaffolds promoted the ordered arrangement of interfacial tissue, reduced scar formation, and significantly strengthened tendon attachment. In vitro, BT guided TDSCs alignment, enhanced expression of tenogenic markers (COL I, SCX and TNMD), suppressed the fibrotic marker α-SMA, and upregulated the antifibrotic factor TGF-β₃, collectively supporting reduced fibrosis and improved stability. Transcriptomic analysis revealed that BT activated the integrin-FAK/Src-MAPK signaling axis, driving tenogenic differentiation while suppressing fibrogenesis, thereby elucidating the molecular mechanism of enhanced tendon-prosthesis integration. Our results demonstrate that BT scaffolds effectively overcome fibrotic tendon-prosthesis interface healing and provide a promising strategy to address the long-standing challenge of insufficient interfacial mechanics in tendon-prosthesis reconstruction.