AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025210203
RESEARCH ARTICLE
Early Access

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

Xianzong Ning2 Rui Du1 Minghao Zhang1 Yutao Yang1 Fei Yu1 Xiaoming Xu2 Baoyuan Meng2 Kai Yan1*
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1 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu province, PR China
2 Division of Sports Medicine and Joint Surgery, Department of Orthopedic Surgery, Nanjing Pukou People's Hospital, Liangjiang Hospital, Southeast University, Nanjing, Jiangsu province, PR China
Received: 19 May 2025 | Accepted: 17 June 2025 | Published online: 17 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

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.

Keywords
3D bioprinting
Silk fibroin
Achilles tendon injury
Heterotopic ossification
Tissue-engineered scaffold
Funding
This work was supported by the National Major Research plan of NSFC (92368201), National Key Research and Development Project (2021YFA1201404), Major Project of NSFC (81991514), Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214).
Conflict of interest
The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing