A spatiotemporally programmed bilayer coating for immunomodulatory and osteogenic enhancement of artificial ligament-bone integration.

Abstract

Polyethylene terephthalate (PET) artificial ligaments have been widely applied in anterior cruciate ligament (ACL) reconstruction due to their excellent mechanical properties. However, their biological inertness often results in poor graft-bone integration, potentially limiting long-term clinical outcomes. Recent studies have highlighted the temporally dynamic nature of the peri-implant microenvironment following implantation, where early-stage oxidative stress, inflammatory responses, and potential bacterial contamination disrupt the transition to vascularized bone regeneration. Therefore, the development of a spatiotemporally responsive interfacial system capable of adapting to this pathological-to-regenerative shift is essential for enhancing the biological performance of synthetic grafts. Here, we propose a bilayered functional coating strategy with phase-specific responsiveness and spatial complementarity. The outer layer comprises a hyaluronic acid-based hydrogel embedded with molybdenum disulfide (MoS₂) nanosheets, enabling early-stage reactive oxygen species (ROS) scavenging and near-infrared (NIR)-activated photothermal antibacterial effects. The inner layer, composed of plasma-sprayed strontium-doped hydroxyapatite (Sr-HA), is activated under stabilized conditions to induce macrophage polarization toward the M2 phenotype and promote angiogenic osteogenesis. In a rat ACL reconstruction model, this bilayered coating significantly improved new bone formation and graft-bone integration. Collectively, this study presents a spatiotemporally programmable interfacial modulation strategy that aligns with the healing rhythm of ACL reconstruction, achieving a closed-loop regulation from early inflammation suppression to late-stage immuno-osteogenic regeneration. This approach offers a mechanistically grounded and translationally promising pathway for functionalizing synthetic ligament grafts.