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ORIGINAL RESEARCH
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PBVHx-based microspheres for controlled BMP2 release and enhanced bone regeneration in a disuse osteoporosis mouse model

Kewen Zhang1,2# ,  Yanwen Zhou3# ,  Daixu Wei3* ,  Airong Qian4* ,  Xiao Lin1,4*
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1 Shenzhen Research Institute of Northwestern Polytechnical University, Shenzhen, Guangdong, China
2 The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen and Longgang District People’s Hospital of Shenzhen, Shenzhen, Guangdong, China
3 Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
4 Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, China
BMT, 00072 https://doi.org/10.12336/bmt.25.00072
Submitted: 25 June 2025 | Revised: 5 August 2025 | Accepted: 6 August 2025 | Published: 4 September 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Addressing bone defects caused by degenerative diseases, trauma, and cancer through bone tissue engineering remains a significant global health challenge. The osteoinductive properties of bone morphogenetic protein-2 (BMP2) have become a key therapeutic strategy in bone regeneration. However, the development of biodegradable composites that ensure biocompatibility, stability, efficient BMP2 loading, and controlled release remains unresolved. In this study, we designed PBVHx/soy lecithin (SL)/BMP2 controlled-release microspheres (sB2PM) based on the biodegradable material poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx), incorporating SL to enable sustained BMP2 delivery and enhance capture. sB2PM microspheres exhibited uniform size (approximately 5 μm) and high BMP2 encapsulation efficiency (80.29%) compared to pure PBVHx-based microspheres (pPM). Due to PBVHx’s biodegradability, BMP2 release was primarily degradation-driven, resulting in a controlled biphasic release profile. sB2PM achieved 62.79% cumulative BMP2 release over four weeks and continued to release BMP2 sustainably thereafter. Co-culturing sB2PM microspheres with human bone marrow-derived mesenchymal stem cells (hBMSCs) in a Transwell system showed enhanced cell proliferation, biocompatibility, and collagen secretion. Compared with pPM and B2PM, sB2PM significantly promoted osteogenic differentiation, increased alkaline phosphatase (ALP) activity, and upregulated osteogenic gene expression in hBMSCs, outperforming commercial hydroxyapatite microspheres. In a mouse hindlimb unloading osteoporosis model, micro computed tomography and histological evaluations confirmed that injectable sB2PM microspheres significantly enhanced bone regeneration, collagen secretion, and ALP and runt-related transcription factor 2 protein expression. This study highlights the potential of sB2PM microspheres with controlled BMP2 release for future bone regeneration therapies.

Keywords
Polyhydroxyalkanoates
Osteoporosis
Controlled release microspheres
Bone morphogenetic protein-2
Mesenchymal stem cells
Funding
This work was supported by grants from the National Natural Science Foundation of China (82470926); the Guangdong Basic and Applied Basic Research Foundation (2023A1515030047); the Natural Science Basic Research Plan in Shaanxi Province of China (2024JC-YBMS-605, 2024JC-YBMS-706); the Health Commission of Sichuan Province Medical Science and Technology Program (24WSXT106); the Collaborative Innovation Project of Zigong Medical Big Data and the Artificial Intelligence Research Institute (2023-YGY-1-02); and the Key Science and Technology Plan Project of Zigong (2022ZCNKY07, 2024-NKY-01-01).
Conflict of interest
The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this work.
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