AccScience Publishing / IJB / Volume 11 / Issue 1 / DOI: 10.36922/ijb.6181
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RESEARCH ARTICLE

Gradient hydroxyapatite nanoparticles with spatial distribution facilitate the healing of tendon-to-bone interface

Lei Wang1,2 ,  Liguo Sun1,3 ,  Zhennan Qiu4,5 ,  Zhao Zhang1 ,  Yubo Shi1,6 ,  Jingyi Dang1 ,  Weidong Tao1 ,  Jiankang He4,5 ,  Hongbin Fan1*
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1 Department of Orthopedic Surgery, Xijing Hospital, the Air Force Military Medical University, Xi’an, Shaanxi, China
2 Department of Orthopaedic Trauma, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
3 Department of Medical Management, Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, Shaanxi, China
4 State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, China
5 Rapid Manufacturing Research Center of Shaanxi Province, Xi’an Jiaotong University, Xi’an, Shaanxi, China
6 Department of Orthopedic Surgery, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei, China
IJB 2025, 11(1), 501–516; https://doi.org/10.36922/ijb.6181
Submitted: 17 November 2024 | Accepted: 31 December 2024 | Published: 2 January 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/ )
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Abstract

Tendon-to-bone interface (TBI) injuries have become increasingly common due to the growing competition in sports. Electrohydrodynamic (EHD) three-dimensional (3D) printing is a promising strategy for controllably fabricating biomimetic micro/ nanoscale architecture in musculoskeletal tissue engineering. This study aims to fabricate a novel biomimetic EHD-printed poly(ε-caprolactone) (PCL) with gradient hydroxyapatite (HA) nanoparticles utilizing modified dopamine self-polymerization reaction and assess the biocompatibility and efficacy of osteogenic differentiation and interface regeneration in vivo. The fabricated scaffold PCL-PDA-HA (PPH) has a diameter of 190.35 ± 41.96 nm in areas with lower HA concentration and 446.54 ± 125.42 nm in areas with higher HA concentration; the scaffold was demonstrated to profoundly facilitate osteogenic differentiation of tendon stem/progenitor cells (TSPCs), enhancing the expression of RUNX2 and ALP. On day 14, the expression of osteogenic genes, including Bmp2 (~3.12-fold, p < 0.001) and Runx2 (~3.24- fold, p < 0.001), was significantly elevated compared to those of PCL groups. New fibrocartilage formation and TBI healing were observed in the PPH group in vivo. Therefore, our work demonstrated a facile green synthesis avenue for enhancing TBI healing via TSPCs’ osteogenic differentiation, which supplied a novel approach to augment the therapeutic effects of ligament graft in TBI reconstruction.

Graphical abstract
Keywords
Gradient
Hydroxyapatite
Tendon-to-bone interface
Tendon stem/progenitor cells
Funding
This work was supported by the National Natural Science Foundation of China (No. 31971272); the International Science and Technology Cooperation Key Program project of Shaanxi Province (No.2023-GHZD-25); and the Rapid Response Project of the Air Force Military Medical University (2023KXKT081).
Conflict of interest
Jiankang He serves as the Editorial Board Member of the journal but was not involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Other 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
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