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Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects
Designing the “ideal” hydrogel/matrix which can load bone morphogenetic protein-2 (BMP-2) in a low dose and with a sustained release is the key for its successful therapeutic application to enhance osteogenesis. The current use of natural collagen sponges as hydrogel/matrix is limited due to the col...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769454/ https://www.ncbi.nlm.nih.gov/pubmed/31487971 http://dx.doi.org/10.3390/biom9090450 |
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author | Chen, Zhuoyue Zhang, Zhen Ma, Xiaoxuan Duan, Zhiguang Hui, Junfeng Zhu, Chenhui Zhang, Donggang Fan, Daidi Shang, Lijun Chen, Fulin |
author_facet | Chen, Zhuoyue Zhang, Zhen Ma, Xiaoxuan Duan, Zhiguang Hui, Junfeng Zhu, Chenhui Zhang, Donggang Fan, Daidi Shang, Lijun Chen, Fulin |
author_sort | Chen, Zhuoyue |
collection | PubMed |
description | Designing the “ideal” hydrogel/matrix which can load bone morphogenetic protein-2 (BMP-2) in a low dose and with a sustained release is the key for its successful therapeutic application to enhance osteogenesis. The current use of natural collagen sponges as hydrogel/matrix is limited due to the collagen matrix showing weak mechanical strength and unmanageable biodegradability. Furthermore, the efficiency and safe dose usage of the BMP-2 has never been seriously considered other than purely chasing the lowest dose usage and extended-release time. In this paper, we customized a novel enzymatically cross-linked recombinant human-like collagen (HLC) sponge with low immunogenicity, little risk from hidden viruses, and easy production. We obtained a unique vertical pore structure and the porosity of the HLC, which are beneficial for Mesenchymal stem cells (MSCs) migration into the HLC sponge and angiopoiesis. This HLC sponge loading with low dose BMP-2 (1 µg) possessed high mechanical strength along with a burst and a sustained release profile. These merits overcome previous limitations of HLC in bone repair and are safer and more sensitive than commercial collagens. For the first time, we identified that a 5 µg dose of BMP-2 can bring about the side effect of bone overgrowth through this sensitive delivery system. Osteoinduction of the HLC-BMP sponges was proved by an in vivo mouse ectopic bone model and a rat cranial defect repair model. The method and the HLC-BMP sponge have the potential to release other growth factors and aid other tissue regeneration. Additionally, the ability to mass-produce HLC in our study overcomes the current supply shortage, which limits bone repair in the clinic. |
format | Online Article Text |
id | pubmed-6769454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67694542019-10-30 Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects Chen, Zhuoyue Zhang, Zhen Ma, Xiaoxuan Duan, Zhiguang Hui, Junfeng Zhu, Chenhui Zhang, Donggang Fan, Daidi Shang, Lijun Chen, Fulin Biomolecules Article Designing the “ideal” hydrogel/matrix which can load bone morphogenetic protein-2 (BMP-2) in a low dose and with a sustained release is the key for its successful therapeutic application to enhance osteogenesis. The current use of natural collagen sponges as hydrogel/matrix is limited due to the collagen matrix showing weak mechanical strength and unmanageable biodegradability. Furthermore, the efficiency and safe dose usage of the BMP-2 has never been seriously considered other than purely chasing the lowest dose usage and extended-release time. In this paper, we customized a novel enzymatically cross-linked recombinant human-like collagen (HLC) sponge with low immunogenicity, little risk from hidden viruses, and easy production. We obtained a unique vertical pore structure and the porosity of the HLC, which are beneficial for Mesenchymal stem cells (MSCs) migration into the HLC sponge and angiopoiesis. This HLC sponge loading with low dose BMP-2 (1 µg) possessed high mechanical strength along with a burst and a sustained release profile. These merits overcome previous limitations of HLC in bone repair and are safer and more sensitive than commercial collagens. For the first time, we identified that a 5 µg dose of BMP-2 can bring about the side effect of bone overgrowth through this sensitive delivery system. Osteoinduction of the HLC-BMP sponges was proved by an in vivo mouse ectopic bone model and a rat cranial defect repair model. The method and the HLC-BMP sponge have the potential to release other growth factors and aid other tissue regeneration. Additionally, the ability to mass-produce HLC in our study overcomes the current supply shortage, which limits bone repair in the clinic. MDPI 2019-09-04 /pmc/articles/PMC6769454/ /pubmed/31487971 http://dx.doi.org/10.3390/biom9090450 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Zhuoyue Zhang, Zhen Ma, Xiaoxuan Duan, Zhiguang Hui, Junfeng Zhu, Chenhui Zhang, Donggang Fan, Daidi Shang, Lijun Chen, Fulin Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects |
title | Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects |
title_full | Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects |
title_fullStr | Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects |
title_full_unstemmed | Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects |
title_short | Newly Designed Human-Like Collagen to Maximize Sensitive Release of BMP-2 for Remarkable Repairing of Bone Defects |
title_sort | newly designed human-like collagen to maximize sensitive release of bmp-2 for remarkable repairing of bone defects |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769454/ https://www.ncbi.nlm.nih.gov/pubmed/31487971 http://dx.doi.org/10.3390/biom9090450 |
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