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ORIGINAL RESEARCH

Recombinant human bone morphogenetic protein-2–engineered piezoplatform synergistically promotes bone regeneration through bone morphogenetic protein receptor activation

Lijie Mao1,2 ,  Dong Zhang1 ,  Zehao Shen1 ,  Xinqing Wang1 ,  Chen Lai3 ,  Fangping Chen1,4* ,  Changsheng Liu1,4*
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1 Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, China
2 Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, China
3 Shenzhen Key Laboratory of Human Tissue Regeneration and Repair, PKU–HKUST ShenZhen–HongKong Institution, Shenzhen, Guangdong, China
4 Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, China
BMT, 19 https://doi.org/10.12336/bmt.25.00019
Submitted: 25 April 2025 | Revised: 23 October 2025 | Accepted: 26 October 2025 | Published: 18 December 2025
© 2025 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

Bone morphogenetic protein-2 (BMP-2) is a potent cytokine that promotes bone formation in orthopedic procedures. However, the delivery of recombinant human BMP-2 (rhBMP-2) with sustained release kinetics, while maximizing osteogenic potential, remains a challenge. In this study, we constructed a novel rhBMP-2–engineered piezoplatform for sustained release of rhBMP-2 and synergistic enhancement of osteoinductive activity. The piezoelectric signals are capable of initiating rapid biomineralization and promoting the early adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs), as well as enabling efficient immobilization and sustained release of rhBMP-2 through electrostatic interactions. Notably, piezoelectric stimulation synergizing with rhBMP-2 enhances osteogenesis-related protein production. This is achieved by amplifying the expression of BMP-2 receptors (Bmpr1a and Bmpr2) in BMSCs by approximately three-fold, which in turn reinforces the regenerative capacity of rhBMP-2. The rat femur defect model further confirms the osteogenic efficacy of the rhBMP-2–engineered piezoplatform. These findings are expected to advance the development of biopiezoelectric implants incorporating growth factor therapy for tissue engineering.

Keywords
Bone morphogenetic protein receptors
Bone regeneration
Piezoelectric stimulation
Recombinant human bone morphogenetic protein-2
Funding
This study was supported by the National Natural Science Foundation of China (32471407, 32171342), the National Key Research and Development Program of China (2023YFC2413600), the Shanghai Pujiang Program (16PJD015), the Joint Fund for Equipment Pre-research of the Ministry of Education (6141A02022618), and the IER Foundation 2021 (IERF202103).
Conflict of interest
The authors declare no conflicts of interest.
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