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International
Journal of Bioprinting
RESEARCH ARTICLE
Three-dimensional bioprinted silk fibroin–
hydroxypropyl cellulose scaffold loaded with
tendon stem/progenitor cells for the prevention
of heterotopic ossification following Achilles
tendon injury
Xianzong Ning 1,2 id , Rui Du 1 id , Minghao Zhang 1 id , Yutao Yang 1 id , Fei Yu 1 id ,
Xiaoming Xu 2 id , Baoyuan Meng 2 id , and Kai Yan *
1 id
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, China
2 Division of Sports Medicine and Joint Surgery, Department of Orthopedic Surgery, Nanjing Pukou
People’s Hospital, Liangjiang Hospital, Southeast University, Nanjing, Jiangsu, China
Abstract
Achilles tendon injury is a common musculoskeletal disorder, particularly prevalent
*Corresponding author: among athletes and middle-aged/elderly populations. Heterotopic ossification
Kai Yan (yank1214@163.com)
(HO) following Achilles tendon injury is a frequent complication that significantly
Citation: Ning X, Du R, Zhang M, compromises patients’ quality of life and athletic performance. Conventional
et al. Three-dimensional bioprinted conservative treatments and surgical interventions for HO often yield suboptimal
silk fibroin–hydroxypropyl cellulose
scaffold loaded with tendon stem/ outcomes, failing to restore native tendon functionality. Tissue engineering strategies
progenitor cells for the prevention integrating biomaterials and cells offer promising solutions for tendon regeneration
of heterotopic ossification following and functional recovery. Three-dimensional bioprinting presents unique advantages
Achilles tendon injury.
Int J Bioprint. 2025;11(4):297-314. in fabricating tissue-engineered scaffolds through precise control of architectural
doi: 10.36922/IJB025210203 geometry and internal microstructure. In this study, we developed a novel silk fibroin
Received: May 19, 2025 (SF)–hydroxypropyl cellulose (HPC)–tendon stem/progenitor cell (TSPC) bioink with
Revised: June 3, 2025 exceptional cytocompatibility and rheological properties. This bioink demonstrated
Accepted: June 17, 2025 superior printability for fabricating porous Achilles tendon scaffolds with high
Published online: June 17, 2025
mechanical strength (elastic modulus: 85 MPa), controlled biodegradability, and
Copyright: © 2025 Author(s). optimal porosity (91%). In vitro experiments revealed that SF– HPC–TSPCs scaffolds
This is an Open Access article
distributed under the terms of the promoted TSPC survival, migration, proliferation, and tenogenic differentiation
Creative Commons Attribution within the scaffold microenvironment. In vivo assessments demonstrated that the
License, permitting distribution, scaffolds exhibited excellent biocompatibility, elicited no systemic inflammatory or
and reproduction in any medium,
provided the original work is immune responses, and effectively prevented HO in rat models of Achilles tendon
properly cited. injury. This study establishes a groundbreaking approach for addressing post-
traumatic HO in tendon regeneration.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Achilles tendon injury; Heterotopic ossification; Silk fibroin;
affiliations. Three-dimensional bioprinting; Tissue-engineered scaffold
Volume 11 Issue 4 (2025) 297 doi: 10.36922/IJB025210203