A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration

Abstract Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse...

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Autores principales:	Daisuke Tateiwa, Shinichi Nakagawa, Hiroyuki Tsukazaki, Rintaro Okada, Joe Kodama, Junichi Kushioka, Zeynep Bal, Yuichiro Ukon, Hiromasa Hirai, Takashi Kaito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d434f4005814c69917236e42c7b0c5c
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spelling	oai:doaj.org-article:3d434f4005814c69917236e42c7b0c5c2021-12-02T18:51:52ZA novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration10.1038/s41598-021-96484-42045-2322https://doaj.org/article/3d434f4005814c69917236e42c7b0c5c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96484-4https://doaj.org/toc/2045-2322Abstract Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse effects. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. In vitro assessment of release kinetics by enzyme-linked immunosorbent assay demonstrated sustained release of rhBMP-2 from NP and burst release from collagen sponge (CS), and in vivo assessment of release kinetics by longitudinal tracking of fluorescently labeled rhBMP-2 showed a longer biological half-life of rhBMP-2 with NP than with CS. Furthermore, osteogenic gene expression in MC3T3-E1 cells was significantly higher after co-culture with NP than after co-culture with CS, suggesting that the sustained release of rhBMP-2 from NP effectively contributed to the differentiation of osteoblasts. In a rat spinal fusion model, the volume and quality of newly formed bone was higher in the NP group than in the CS group. Use of NP results in efficient bone regeneration through sustained release of rhBMP-2 and improves the quality of BMP-induced bone.Daisuke TateiwaShinichi NakagawaHiroyuki TsukazakiRintaro OkadaJoe KodamaJunichi KushiokaZeynep BalYuichiro UkonHiromasa HiraiTakashi KaitoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daisuke Tateiwa Shinichi Nakagawa Hiroyuki Tsukazaki Rintaro Okada Joe Kodama Junichi Kushioka Zeynep Bal Yuichiro Ukon Hiromasa Hirai Takashi Kaito A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
description	Abstract Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse effects. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. In vitro assessment of release kinetics by enzyme-linked immunosorbent assay demonstrated sustained release of rhBMP-2 from NP and burst release from collagen sponge (CS), and in vivo assessment of release kinetics by longitudinal tracking of fluorescently labeled rhBMP-2 showed a longer biological half-life of rhBMP-2 with NP than with CS. Furthermore, osteogenic gene expression in MC3T3-E1 cells was significantly higher after co-culture with NP than after co-culture with CS, suggesting that the sustained release of rhBMP-2 from NP effectively contributed to the differentiation of osteoblasts. In a rat spinal fusion model, the volume and quality of newly formed bone was higher in the NP group than in the CS group. Use of NP results in efficient bone regeneration through sustained release of rhBMP-2 and improves the quality of BMP-induced bone.
format	article
author	Daisuke Tateiwa Shinichi Nakagawa Hiroyuki Tsukazaki Rintaro Okada Joe Kodama Junichi Kushioka Zeynep Bal Yuichiro Ukon Hiromasa Hirai Takashi Kaito
author_facet	Daisuke Tateiwa Shinichi Nakagawa Hiroyuki Tsukazaki Rintaro Okada Joe Kodama Junichi Kushioka Zeynep Bal Yuichiro Ukon Hiromasa Hirai Takashi Kaito
author_sort	Daisuke Tateiwa
title	A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
title_short	A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
title_full	A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
title_fullStr	A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
title_full_unstemmed	A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
title_sort	novel bmp-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d434f4005814c69917236e42c7b0c5c
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A novel BMP-2–loaded hydroxyapatite/beta-tricalcium phosphate microsphere/hydrogel composite for bone regeneration

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