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.
Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties. Furthermore, their biological performance was assessed using tendon stem/progenitor cells (TSPCs). Micro-nanofibers induced a higher cell aspect ratio and enhanced the tenogenic differentiation of TSPCs compared to micro- and nanocontrols. Interestingly, it was observed that scaffold nanotopography and microstructures promoted tenogenesis via activating the TGF-β/Smad2/3-mediated signaling pathway. The in situ implantation study confirmed that micro-nanofibrous scaffolds promoted the structural and mechanical properties of the regenerated Achilles tendon. Overall, our study shows that the bimodal micro-nanofibrous scaffold developed here presents a promising potential to improve the outcomes of tendon tissue engineering.
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