Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK

Polyether ether ketone (PEEK)–based biomaterials have been widely used in the field of spine and joint surgery. However, lack of biological activity limits their further clinical application. In this study, we synthesized a bioclickable mussel-derived peptide Azide-DOPA4 as a PEEK surface coating mo...

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Autores principales:	Huan Zhao, Xiaokang Wang, Wen Zhang, Lin Wang, Can Zhu, Yingkang Huang, Rongrong Chen, Xu Chen, Miao Wang, Guoqing Pan, Qin Shi, Xichao Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PEEK clickable mussel-biomimetic peptide bone morphogenetic protein 2 functional peptides bio-orthogonal reaction osseointegration FOXP3+ regulatory T cells Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/b58ee91af6ea4fa5b90089c07bba18a0
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spelling	oai:doaj.org-article:b58ee91af6ea4fa5b90089c07bba18a02021-11-30T17:52:38ZBioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK2296-418510.3389/fbioe.2021.780609https://doaj.org/article/b58ee91af6ea4fa5b90089c07bba18a02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.780609/fullhttps://doaj.org/toc/2296-4185Polyether ether ketone (PEEK)–based biomaterials have been widely used in the field of spine and joint surgery. However, lack of biological activity limits their further clinical application. In this study, we synthesized a bioclickable mussel-derived peptide Azide-DOPA4 as a PEEK surface coating modifier and further combined bone morphogenetic protein 2 functional peptides (BMP2p) with a dibenzylcyclooctyne (DBCO) motif through bio-orthogonal reactions to obtain DOPA4@BMP2p-PEEK. As expected, more BMP2p can be conjugated on PEEK after Azide-DOPA4 coating. The surface roughness and hydrophilicity of DOPA4@BMP2p-PEEK were obviously increased. Then, we optimized the osteogenic capacity of PEEK substrates. In vitro, compared with the BMP2p-coating PEEK material, DOPA4@BMP2p-PEEK showed significantly higher osteogenic induction capability of rat bone marrow mesenchymal stem cells. In vivo, we constructed a rat calvarial bone defect model and implanted PEEK materials with a differently modified surface. Micro-computed tomography scanning displayed that the DOPA4@BMP2p-PEEK implant group had significantly higher new bone volume and bone mineral density than the BMP2p-PEEK group. Histological staining of hard tissue further confirmed that the DOPA4@BMP2p-PEEK group revealed a better osseointegrative effect than the BMP2p-PEEK group. More importantly, we also found that DOPA4@BMP2p coating has a synergistic effect with induced Foxp3+ regulatory T (iTreg) cells to promote osteogenesis. In summary, with an easy-to-perform, two-step surface bioengineering approach, the DOPA4@BMP2p-PEEK material reported here displayed excellent biocompatibility and osteogenic functions. It will, moreover, offer insights to engineering surfaces of orthopedic implants.Huan ZhaoXiaokang WangXiaokang WangWen ZhangLin WangCan ZhuYingkang HuangRongrong ChenXu ChenMiao WangGuoqing PanQin ShiXichao ZhouFrontiers Media S.A.articlePEEKclickable mussel-biomimetic peptidebone morphogenetic protein 2 functional peptidesbio-orthogonal reactionosseointegrationFOXP3+ regulatory T cellsBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PEEK clickable mussel-biomimetic peptide bone morphogenetic protein 2 functional peptides bio-orthogonal reaction osseointegration FOXP3+ regulatory T cells Biotechnology TP248.13-248.65
spellingShingle	PEEK clickable mussel-biomimetic peptide bone morphogenetic protein 2 functional peptides bio-orthogonal reaction osseointegration FOXP3+ regulatory T cells Biotechnology TP248.13-248.65 Huan Zhao Xiaokang Wang Xiaokang Wang Wen Zhang Lin Wang Can Zhu Yingkang Huang Rongrong Chen Xu Chen Miao Wang Guoqing Pan Qin Shi Xichao Zhou Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK
description	Polyether ether ketone (PEEK)–based biomaterials have been widely used in the field of spine and joint surgery. However, lack of biological activity limits their further clinical application. In this study, we synthesized a bioclickable mussel-derived peptide Azide-DOPA4 as a PEEK surface coating modifier and further combined bone morphogenetic protein 2 functional peptides (BMP2p) with a dibenzylcyclooctyne (DBCO) motif through bio-orthogonal reactions to obtain DOPA4@BMP2p-PEEK. As expected, more BMP2p can be conjugated on PEEK after Azide-DOPA4 coating. The surface roughness and hydrophilicity of DOPA4@BMP2p-PEEK were obviously increased. Then, we optimized the osteogenic capacity of PEEK substrates. In vitro, compared with the BMP2p-coating PEEK material, DOPA4@BMP2p-PEEK showed significantly higher osteogenic induction capability of rat bone marrow mesenchymal stem cells. In vivo, we constructed a rat calvarial bone defect model and implanted PEEK materials with a differently modified surface. Micro-computed tomography scanning displayed that the DOPA4@BMP2p-PEEK implant group had significantly higher new bone volume and bone mineral density than the BMP2p-PEEK group. Histological staining of hard tissue further confirmed that the DOPA4@BMP2p-PEEK group revealed a better osseointegrative effect than the BMP2p-PEEK group. More importantly, we also found that DOPA4@BMP2p coating has a synergistic effect with induced Foxp3+ regulatory T (iTreg) cells to promote osteogenesis. In summary, with an easy-to-perform, two-step surface bioengineering approach, the DOPA4@BMP2p-PEEK material reported here displayed excellent biocompatibility and osteogenic functions. It will, moreover, offer insights to engineering surfaces of orthopedic implants.
format	article
author	Huan Zhao Xiaokang Wang Xiaokang Wang Wen Zhang Lin Wang Can Zhu Yingkang Huang Rongrong Chen Xu Chen Miao Wang Guoqing Pan Qin Shi Xichao Zhou
author_facet	Huan Zhao Xiaokang Wang Xiaokang Wang Wen Zhang Lin Wang Can Zhu Yingkang Huang Rongrong Chen Xu Chen Miao Wang Guoqing Pan Qin Shi Xichao Zhou
author_sort	Huan Zhao
title	Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK
title_short	Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK
title_full	Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK
title_fullStr	Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK
title_full_unstemmed	Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK
title_sort	bioclickable mussel-derived peptides with immunoregulation for osseointegration of peek
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b58ee91af6ea4fa5b90089c07bba18a0
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Bioclickable Mussel-Derived Peptides With Immunoregulation for Osseointegration of PEEK

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