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ORIGINAL RESEARCH

PDGF-BB–functionalized 3D-printed PLGA/MgP scaffold promotes diabetic bone defect regeneration through angiogenesis and immune modulation

Zecai Chen1,2# ,  Qingsong Zhang3# ,  Jun Chen3# ,  Yafang Huang3 ,  Xiayi Zhou1 ,  Wei Li1 ,  Wei You1 ,  Yonghui Yang3 ,  Dan Yang3 ,  Jie Wang3 ,  Wenzhao Wang4,5* ,  Jie Tan2,3* ,  Chuanxi Zheng1*
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1 Department of Musculoskeletal Oncology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
2 Department of Spine Surgery & Innovative Laboratory of Orthopedics, Shenzhen Nanshan People’s Hospital, The Affiliated Nanshan Hospital of Shenzhen University, Shenzhen, Guangdong, China
3 Hubei Key Laboratory of Sports Injury and Precision Therapy, Wuhan Fourth Hospital, Wuhan, Hubei, China
4 Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, China
5 Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
BMT, 52 https://doi.org/10.12336/bmt.26.00052
Submitted: 26 March 2026 | Revised: 14 April 2026 | Accepted: 16 April 2026 | Published: 20 May 2026
© 2026 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
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Abstract

The management of diabetic bone defects remains a critical challenge due to the inherently disturbed microenvironment, in which uncontrolled inflammation and impaired angiogenesis are hallmark features of this condition. In this study, we developed a novel composite three-dimensional (3D)-printed scaffold by integrating magnesium phosphate (MgP) into the 3D-printed poly(lactide-co-glycolide) (PLGA) framework, followed by functionalization of platelet-derived growth factor–BB (PDGF-BB) via a gelatin methacryloyl coating. This design enabled spatiotemporally controlled release of PDGF-BB, magnesium ions, and phosphate ions from the composite scaffold. After PDGF-BB functionalization, the composite scaffold (PMGp) suppressed M1 polarization and significantly enhanced the recruitment, migration, and tube formation capacity of human umbilical vein endothelial cells at the early stage. Transcriptomic analysis revealed that the anti-inflammatory and pro-regenerative effects of the scaffold were mediated through suppression of key signaling pathways, including interleukin-17, Toll-like receptor, Janus kinase–signal transducer and activator of transcription, and tumor necrosis factor pathways. In addition, enhanced osteogenic differentiation of MC3T3-E1 cells, as evidenced by alkaline phosphatase (ALP) activity and Alizarin Red S staining, was observed in the PMGp group. In vivo implantation of the PMGp scaffold improved bone regeneration in a diabetic rat bone defect model, demonstrating increased bone volume fraction and bone mineral density, along with the formation of mature lamellar bone. Notably, a favorable shift in the M1/M2 macrophage balance, increased expression of osteogenic markers (e.g., ALP and osteocalcin), reduced osteoclast activity (tartrate-resistant acid phosphatase staining), and enhanced neovascularization (CD31 immunostaining) were also confirmed through histological and immunofluorescent analyses. These findings suggest a multifunctional strategy for treating diabetic bone defects by modulating inflammation while promoting angiogenesis and osteogenesis, providing a strong basis for future translational research.

Keywords
Diabetic bone defect
Three-dimensional printing
Immunomodulation
Angiogenesis
Funding
This research was jointly supported by the National Natural Science Foundation of China Youth Fund Project (82402772), Guangdong Basic and Applied Basic Research Foundation (2023A1515220007), Hubei Natural Science Foundation (2025AFB814), China International Medical Foundation Project (Z-2017- 24-2509), Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP007), Foundation of National Center for Translational Medicine (Shanghai) SHU Branch (SUITM-202505), Shenzhen Science and Technology Program (JCYJ20240813141004007), Wuhan Natural Science Foundation Exploratory Project (Chenguang Program) (2024020801020399 and 2025040601020210), Youth Project of Wuhan Health Commission (WX23Z08), Hubei Province Postdoctoral Pioneer Talent Follow-up Support Program, Wuhan Chengxing Talent Program, Shandong Provincial Education Department Project (2024KJJ078), and Young Talent of Lifting engineering for Science and Technology in Shandong (SDAST2025QTA009).
Conflict of interest
The authors declare that they have no competing interests.
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