Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose
Open accessAbstract
Introduction: To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2) are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods: A new growth factor delivery system was fabricated using BMP-2-loaded TiO 2 nanotubes by lyophilization with trehalose (TiO 2 -Lyo-Tre-BMP-2). We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT), sequential fluorescent labelling, and histological analysis. Results: Compared with absorbed BMP-2-loaded TiO 2 nanotubes (TiO 2 -BMP-2), TiO 2 -Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO 2 -Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO 2 -BMP-2 nanotubes. Conclusion: Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects. Keywords: bone morphogenetic protein-2, dose reduction, delivery system, trehalose, lyophilization, TiO 2 nanotubes, BMP-2, regenerative medicine, surface modification
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Cryopreservation methods that have been reported to enhance rhBMP-2 bioactivity were not used.
“and we did not use cryopreservation methods that have been reported to enhance rhBMP-2 bioactivity [43].”
From Keratin Scaffold Formulation Impacts rhBMP-2 Biodistribution and Bone Regeneration in a Rat Femur Defect Model (2025) · cites this paper as [43]
The Discussion (page unavailable) says lyophilization with trehalose maintained BMP-2 bioactivity, and the Results report retention after storage at −20°C. The paper describes freeze-drying, not cryopreservation, and reports no significant bioactivity difference between treated and fresh BMP-2; it therefore does not support the claim that cryopreservation enhances rhBMP-2 bioactivity. (LLM, conf=0.83)
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- Authors
- Zhang, X., Yu, Q., Wang, Y.-A., & Zhao, J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2018-01
- Volume
- Volume 13
- Pages
- 403-414
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC5769568
- OpenAlex
- W2783350834
- Cited by
- 25
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 4
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Natural Science Foundation of China (81470765, 81200815, 81371164)
- Science and Technology Commission of Shanghai Municipality (17441902000)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- BMP-2, trehalose, freeze-drying, TiO2 nanotubes, growth factor delivery systems, sustained drug release, osteogenic differentiation, mesenchymal stem cells, bone regeneration, bone defects, rat femur, surface modification
- MeSH terms
- Animals, Bone Regeneration, Cell Differentiation, Dose-Response Relationship, Drug, Freeze Drying, Male, Osteogenesis, Rats, Inbred F344, Titanium, Trehalose, Drug Delivery Systems, Nanotubes, Cell Proliferation, X-Ray Microtomography, Bone Morphogenetic Protein 2, Mesenchymal Stem Cells, Drug Liberation
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