AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025380386
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RESEARCH ARTICLE

Synergistic bone regeneration by surface-modified 3D-printed PCL/β-TCP scaffolds in various animal defect models

Yulin Jiang1 ,  Guanghui Xi1 ,  Chen Zhou1 ,  Haisong Xu3* ,  Xi Yang1* ,  Dongxu Ke1,2*
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1 Novaprint Therapeutics Suzhou Co., Ltd., Suzhou, Jiangsu, China
2 Department of Biomedical Engineering, Nanjing University Suzhou Campus, Suzhou, Jiangsu, China
3 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
IJB, 025380386 https://doi.org/10.36922/IJB025380386
Received: 17 September 2025 | Accepted: 3 November 2025 | Published online: 3 November 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

The regeneration of large-segmental bone defects remains a significant clinical challenge due to their complex microenvironments. Three-dimensional (3D)-printed polycaprolactone (PCL) scaffolds offer a potential solution but exhibit limited osteoinductive capacity. In this study, 3D-printed PCL/β-tricalcium phosphate (TCP) composite scaffolds were pretreated with NaOH, followed by functionalization with bioactive collagen and β‑TCP. These modifications markedly improved the scaffolds’ hydrophilicity without compromising mechanical integrity. In vitro studies with MC3T3-E1 cells demonstrated that the CS@TCP scaffolds significantly enhanced early osteogenic differentiation compared to C, CS, and CS@COL scaffolds, as indicated by the alkaline phosphatase activity assay. In vivo evaluation using three different rabbit cranial defect models revealed superior new bone formation in the partial-thickness cranial defect (PTD) groups compared to the full-thickness cranial defect (FTD) and intact cranial bone onlay (Onlay) groups, potentially due to the increased vascularization and abundant endogenous stem cells in the PTD groups. Despite reduced new bone formation in the Onlay group, its bone integration advantages may be advantageous for cosmetic surgery applications. This study investigated how β‑TCP surface modification interacts with clinical application-specific microenvironments to maximize the regenerative potential of 3D-printed scaffolds, providing crucial guidance for scaffold design in effective bone defect repair across various clinical scenarios.

 

Graphical abstract
Keywords
3D-printed scaffolds
In vitro proliferation and differentiation
Multiple animal defect models
Surface modification
Funding
The study was funded by the Natural Science Foundation of Jiangsu Province (BK20210117).
Conflict of interest
Yulin Jiang, Guanghui Xi, Chen Zhou, Xi Yang, and Dongxu Ke are employees of Novaprint Therapeutics Suzhou Co., Ltd during this study but had no involvement in activities posing a conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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