Prolonged release of bone morphogenetic protein-2 in vivo by gene transfection with DNA-functionalized calcium phosphate nanoparticle-loaded collagen scaffolds
Abstract
In the combination of scaffolds immersed in growth factor solutions, the release of growth factors mainly depends on scaffold degradation. However, the release of bone morphogenetic protein (BMP)-2 at an appropriate concentration during the stage of tissue regeneration would enhance bone regeneration. To achieve this condition, the present study was performed to investigate the effects of scaffolds combined with gene transfection using non-viral vectors. Nanohydroxyapatite-collagen (nHAC) scaffolds cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) or ascorbic acid/copper chloride, and a collagen scaffold (Terdermis®) were prepared, loaded with BMP-2-encoding plasmid DNA-functionalized calcium phosphate nanoparticles (CaP), naked plasmid DNA, or BMP-2 solution, and implanted in rats. The yield of released BMP-2 and its releasing period, respectively, were larger and longer from the scaffolds loaded with CaP than from those incubated with BMP-2 solution. In addition, the alkaline phosphatase activity induced by the CaP-loaded scaffolds was higher. Histological analysis showed that released BMP-2 could be observed on the macrophages or multinuclear giant cells surrounding the nHAC fragments or collagen fibres. TRAP-positive or OCN-positive sites were observed in all groups and a mineralization area was observed in the Terdermis®/CaP sample. The present study demonstrates that gene transfection by scaffold loaded with CaP gene transfer vectors induces a larger yield of BMP-2 for a longer period than by scaffolds loaded with BMP-2 solution or naked plasmid.
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Physical crosslinkers such as ultraviolet rays have the potential to break down and denature collagen.
“The physical crosslinkers such as ultraviolet rays have the potential to break down and denature the collagen [120] which may deteriorate the overall mechanical properties.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [120]
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Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration.
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- Authors
- Tenkumo, T., Vanegas Sáenz, J. R., Nakamura, K., Shimizu, Y., Sokolova, V., Epple, M., Kamano, Y., Egusa, H., Sugaya, T., & Sasaki, K.
- Affiliations
- Tohoku University (JP)
- University of Duisburg-Essen (DE)
- Hokkaido University (JP)
- Corresponding author
- Tenkumo, Taichi
- ORCID
- Venue
- Materials Science and Engineering: C
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 92
- Pages
- 172-183
- ISSN
- 0928-4931 (ISSN-L)
- OpenAlex
- W2810888458
- Cited by
- 46
- References
- 42
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 3
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Materials Science and Engineering C (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Dentistry › Oral Surgery › Dental Implant Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- BMP-2, sustained growth factor release, calcium phosphate nanoparticles, collagen scaffolds, hydroxyapatite nanoparticles, transfection, non-viral gene delivery, bone regeneration, alkaline phosphatase activity, EDC crosslinking, bone mineralization, macrophages
- MeSH terms
- Alkaline Phosphatase, Animals, Ascorbic Acid, Carbodiimides, Collagen, DNA, Drug Carriers, Male, Plasmids, Skin, Osteocalcin, Rats, Wistar, Durapatite, Prosthesis Implantation, Rats, X-Ray Microtomography, Bone Morphogenetic Protein 2
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