3D bioprinted silk fibroin-hydroxypropyl cellulose-tendon stem/progenitor cells tissue-engineered scaffold for preventing heterotopic ossification after Achilles tendon injury

Achilles tendon injury is a common musculoskeletal disorder, particularly prevalent among athletes and middle-aged/elderly populations. Heterotopic ossification following Achilles tendon injury represents a frequent complication that severely compromises patients' quality of life and athletic performance. Conventional conservative treatments and surgical interventions for heterotopic ossification often yield suboptimal outcomes, failing to restore native tendon functionality. Tissue engineering strategies integrating biomaterials and cells offer promising solutions for tendon regeneration and functional recovery. 3D bioprinting demonstrates unique advantages in fabricating tissue-engineered scaffolds through precise control of architectural geometry and internal microstructure. In this study, we developed a novel silk fibroin-hydroxypropyl cellulose-tendon stem/progenitor cells bioink with exceptional cytocompatibility and rheological properties, which demonstrated superior printability for fabricating porous Achilles tendon scaffolds with high mechanical strength (elastic modulus: 85 MPa), controlled biodegradability, and optimal porosity (91%). In vitro experiments revealed that silk fibroin-hydroxypropyl cellulose-tendon stem/progenitor cells scaffolds promoted tendon stem/progenitor cells survival, migration, proliferation, and tenogenic differentiation within the scaffold microenvironment. In vivo assessments demonstrated excellent biocompatibility of the scaffolds, showing no systemic inflammatory or immune responses while effectively preventing heterotopic ossification formation in rat models of Achilles tendon injury. This study establishes a groundbreaking approach for addressing post-traumatic heterotopic ossification in tendon regeneration.