Three-dimensional bioprinted silk fibroin-hydroxypropyl cellulose scaffold loaded with tendon stem/progenitor cells for the prevention of heterotopic ossification following Achilles tendon injury

Abstract

Achilles tendon injury is a common musculoskeletal disorder, particularly prevalent among athletes and middle-aged/elderly populations. Heterotopic ossification (HO) following Achilles tendon injury is a frequent complication that significantly compromises patients’ quality of life and athletic performance. Conventional conservative treatments and surgical interventions for HO 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. Three-dimensional bioprinting presents 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 (SF)-hydroxypropyl cellulose (HPC)-tendon stem/progenitor cell (TSPC) bioink with exceptional cytocompatibility and rheological properties. This bioink 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 SF- HPC-TSPCs scaffolds promoted TSPC survival, migration, proliferation, and tenogenic differentiation within the scaffold microenvironment. In vivo assessments demonstrated that the scaffolds exhibited excellent biocompatibility, elicited no systemic inflammatory or immune responses, and effectively prevented HO in rat models of Achilles tendon injury. This study establishes a groundbreaking approach for addressing post-traumatic HO in tendon regeneration.

Keywords

Achilles tendon injury / Heterotopic ossification / Silk fibroin / Three-dimensional bioprinting / Tissue-engineered scaffold

Funding

This work was supported by the National Major Research Plan of the National Natural Science Foundation of China (NSFC) (92368201), the National Key Research and Development Project (2021YFA1201404), the Major Project of NSFC (81991514), and the Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214).

Conflict of interest

The authors declare that they have no competing interests.

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