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Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone
Masahito Hara1,2, Yoshinori Sumita2, Yukinobu Kodama3
1Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
Materials (Basel, Switzerland)
|November 27, 2021
Summary
New nanoballs, a biocompatible nucleic acid carrier, efficiently deliver DNA for bone regeneration. These nanoballs promote significant bone augmentation with minimal DNA, outperforming naked DNA in gene-activated matrices.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Nanotechnology
Background:
- Developing effective nucleic acid carriers is crucial for gene therapy and tissue regeneration.
- Nanoballs, biocompatible self-assembly nano-vectors, show promise for in vivo nucleic acid delivery due to low cytotoxicity and high transfection efficiency.
Purpose of the Study:
- To investigate the efficacy of a gene-activated matrix (GAM) using nanoballs carrying plasmid DNA encoding bone morphogenetic protein 4 (pBMP4) for bone augmentation.
- To compare the bone regenerative capacity of pBMP4-loaded nanoballs within a GAM versus naked pBMP4.
Main Methods:
- Constructed BMP4-nanoballs using pBMP4, dendrigraft poly-L-lysine (DGL), and γ-polyglutamic acid (γ-PGA).
- Prepared GAMs by combining BMP4-nanoballs with atelocollagen and β-tricalcium phosphate (β-TCP) granules.
- Transplanted GAMs to rat cranial bone surfaces and evaluated bone augmentation over 8 weeks.
Main Results:
- BMP4-nanoballs were readily taken up by macrophages and mesenchymal progenitor cells, promoting anti-inflammatory and osteoblastic differentiation.
- Significant bone augmentation was observed in GAMs containing BMP4-nanoballs.
- A mere 1 μg of BMP4-nanoballs achieved comparable bone regeneration to 1000 μg of naked pDNAs.
Conclusions:
- BMP4-nanoballs effectively promote bone augmentation within a GAM, demonstrating superior efficiency compared to naked DNA.
- This anionic nano-vector, when integrated into appropriate matrices, shows significant potential for bone engineering applications.
