Trans-Tissue Photothermal Stimulation Accelerates In Situ Repair after ACL Reconstruction: Calcium/Copper Reservoir Scaffold-Mediated Strategy

Rapid rehabilitation of the ligament-bone interface following anterior cruciate ligament (ACL) reconstruction remains challenging due to poor vascularization and inadequate integration between graft, bone tunnel, and scaffold. Conventional rehabilitation stimuli are limited by their shallow tissue penetration, which fails to effectively target the bone tunnel. This study proposes a synergistic strategy using a dual calcium/copper reservoir-functionalized scaffold with trans-tissue mild photothermal therapy (mPTT, 40–42 °C) to promote phase-specific healing.​ A 3D-printed polyetherimide (PEI) scaffold incorporating Calcium carbonate (CaCO 3 ) serves as a calcium reservoir, while it is modified with a Cupric oxide-polydopamine (CuO-PDA) coating, serving both as a copper reservoir and a photothermal agent. Upon implantation, the rapid release of Cu 2+ accelerates early-stage vascularization, while sustained release of Ca 2+ creates a calcium-enriched osteogenic microenvironment, promoting osteogenic differentiation and bone regeneration. Crucially, near-infrared light-triggered activation of the CuO-PDA coating enables trans-tissue mPTT. This upregulates heat shock protein expression, which synergistically enhances reservoir-driven osteogenesis and collagen remodeling. This study marks the first application of mPTT in ligament-bone healing. This synergistic platform facilitates direct thermal stimulation and in situ repair at the ACL reconstruction site, offering a novel therapeutic strategy to enhance post-surgical recovery following ligament reconstruction with bone–interface fixation scaffolds.