Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation

We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investig...

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Autores principales:	Masahito Hara, Yoshinori Sumita, Yukinobu Kodama, Mayumi Iwatake, Hideyuki Yamamoto, Rena Shido, Shun Narahara, Takunori Ogaeri, Hitoshi Sasaki, Izumi Asahina
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bone augmentation in vivo gene delivery gene-activated matrix plasmid vector self-assembly nano-device Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85
Acceso en línea:	https://doaj.org/article/f565e59bc16c48db8245e49dc5e5ee38
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spelling	oai:doaj.org-article:f565e59bc16c48db8245e49dc5e5ee382021-11-25T18:16:19ZGene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation10.3390/ma142270971996-1944https://doaj.org/article/f565e59bc16c48db8245e49dc5e5ee382021-11-01T00:00:00Zhttps://www.mdpi.com/1996-1944/14/22/7097https://doaj.org/toc/1996-1944We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing plasmid (p) DNAs encoding bone morphogenetic protein 4 (pBMP4) could promote bone augmentation with a small amount of DNA compared to that composed of naked pDNAs. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (DGL, a cationic polymer) coated by γ-polyglutamic acid (γ-PGA; an anionic polymer), and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and β-tricalcium phosphate (β-TCP) granules and lyophilizing them for bone augmentation. The GAMs were then transplanted to rat cranial bone surfaces under the periosteum. From the initial stage, infiltrated macrophages and mesenchymal progenitor cells took up the nanoballs, and their anti-inflammatory and osteoblastic differentiations were promoted over time. Subsequently, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 1 μg of BMP4-nanoballs induced a sufficient volume of new bone, while 1000 μg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to the appropriate matrices can facilitate GAM-based bone engineering.Masahito HaraYoshinori SumitaYukinobu KodamaMayumi IwatakeHideyuki YamamotoRena ShidoShun NaraharaTakunori OgaeriHitoshi SasakiIzumi AsahinaMDPI AGarticlebone augmentationin vivo gene deliverygene-activated matrixplasmid vectorself-assembly nano-deviceTechnologyTElectrical engineering. Electronics. Nuclear engineeringTK1-9971Engineering (General). Civil engineering (General)TA1-2040MicroscopyQH201-278.5Descriptive and experimental mechanicsQC120-168.85ENMaterials, Vol 14, Iss 7097, p 7097 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone augmentation in vivo gene delivery gene-activated matrix plasmid vector self-assembly nano-device Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85
spellingShingle	bone augmentation in vivo gene delivery gene-activated matrix plasmid vector self-assembly nano-device Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85 Masahito Hara Yoshinori Sumita Yukinobu Kodama Mayumi Iwatake Hideyuki Yamamoto Rena Shido Shun Narahara Takunori Ogaeri Hitoshi Sasaki Izumi Asahina Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation
description	We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing plasmid (p) DNAs encoding bone morphogenetic protein 4 (pBMP4) could promote bone augmentation with a small amount of DNA compared to that composed of naked pDNAs. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (DGL, a cationic polymer) coated by γ-polyglutamic acid (γ-PGA; an anionic polymer), and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and β-tricalcium phosphate (β-TCP) granules and lyophilizing them for bone augmentation. The GAMs were then transplanted to rat cranial bone surfaces under the periosteum. From the initial stage, infiltrated macrophages and mesenchymal progenitor cells took up the nanoballs, and their anti-inflammatory and osteoblastic differentiations were promoted over time. Subsequently, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 1 μg of BMP4-nanoballs induced a sufficient volume of new bone, while 1000 μg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to the appropriate matrices can facilitate GAM-based bone engineering.
format	article
author	Masahito Hara Yoshinori Sumita Yukinobu Kodama Mayumi Iwatake Hideyuki Yamamoto Rena Shido Shun Narahara Takunori Ogaeri Hitoshi Sasaki Izumi Asahina
author_facet	Masahito Hara Yoshinori Sumita Yukinobu Kodama Mayumi Iwatake Hideyuki Yamamoto Rena Shido Shun Narahara Takunori Ogaeri Hitoshi Sasaki Izumi Asahina
author_sort	Masahito Hara
title	Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation
title_short	Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation
title_full	Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation
title_fullStr	Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation
title_full_unstemmed	Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation
title_sort	gene-activated matrix with self-assembly anionic nano-device containing plasmid dnas for rat cranial bone augmentation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f565e59bc16c48db8245e49dc5e5ee38
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Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation

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