A Biomimetic Janus Fibrous Membrane for Scarless Achilles Tendon Regeneration via Synergistic Modulation of an Oxidative-Inflammatory Cascade

Achilles tendon injuries present significant clinical challenges due to limited regenerative capacity and frequent adhesion formation. Here, we report a melatonin-loaded Janus fibrous membrane (MLT@JFM) that mimics the native paratenon’s structure and function to promote scarless tendon healing. The biomimetic membrane consists of an inner methacrylated silk fibroin (SFMA) layer that promotes tendon stem cell functions and an outer melatonin-loaded polycaprolactone methacryloyl (PCLMA) layer that prevents adhesion formation. Through photo-cross-linking and structural interlocking, MLT@JFM achieves excellent mechanical properties and stable fixation around injured tendons. In vitro studies demonstrate that MLT@JFM effectively scavenges reactive oxygen species, modulates macrophage polarization, and maintains tendon stem cell phenotype under inflammatory conditions. In a rat Achilles tendon injury model, MLT@JFM significantly enhances functional recovery and biomechanical properties while preventing adhesion formation. Transcriptomic analysis reveals that MLT@JFM promotes scarless healing through synergistic regulation of oxidative-inflammatory cascades and the enhancement of tissue regeneration. This study presents MLT@JFM as a promising therapeutic strategy for tendon repair and provides new insights into biomaterial-mediated tissue regeneration.