Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2
The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-pre...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.920696/full |
| _version_ | 1811289003045945344 |
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| author | Gaoli Xu Gaoli Xu Chenxi Shen Chenxi Shen Haiyan Lin Haiyan Lin Jian Zhou Ting Wang Ben Wan Ben Wan Munerah Binshabaib Tymour Forouzanfar Guochao Xu Nawal Alharbi Gang Wu Gang Wu |
| author_facet | Gaoli Xu Gaoli Xu Chenxi Shen Chenxi Shen Haiyan Lin Haiyan Lin Jian Zhou Ting Wang Ben Wan Ben Wan Munerah Binshabaib Tymour Forouzanfar Guochao Xu Nawal Alharbi Gang Wu Gang Wu |
| author_sort | Gaoli Xu |
| collection | DOAJ |
| description | The repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the in-vivo osteoinductive efficacy in a subcutaneous bone induction model in rats. In-vitro characterization data showed that the BpNcCaP + BMP-2 granules were comprised of hexagonal hydroxyapatite with an average crystallite size ranging from 19.7 to 25.1 nm and a grain size at 84.13 ± 28.46 nm. The vickers hardness of BpNcCaP was 32.50 ± 3.58 HV 0.025. BpNcCaP showed no obvious cytotoxicity and was favorable for the adhesion of pre-osteoblasts. BMP-2 incorporation rate could be as high as 65.04 ± 6.01%. In-vivo histomorphometric analysis showed that the volume of new bone induced by BpNcCaP exhibited a BMP-2 amount-dependent increasing manner. The BpNcCaP+50 μg BMP-2 exhibited significantly more degradation and fewer foreign body giant cells in comparison with BpNcCaP. These data suggested a promising application potential of BpNcCaP + BMP-2 in repairing LVBDs. |
| first_indexed | 2024-04-13T03:47:16Z |
| format | Article |
| id | doaj.art-c15ea532fac141369335f70895689415 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-13T03:47:16Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-c15ea532fac141369335f708956894152022-12-22T03:03:59ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-07-011010.3389/fbioe.2022.920696920696Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2Gaoli Xu0Gaoli Xu1Chenxi Shen2Chenxi Shen3Haiyan Lin4Haiyan Lin5Jian Zhou6Ting Wang7Ben Wan8Ben Wan9Munerah Binshabaib10Tymour Forouzanfar11Guochao Xu12Nawal Alharbi13Gang Wu14Gang Wu15Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam, NetherlandsDepartment of Stomatology, Zhejiang Hospital, Hangzhou, ChinaDepartment of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam, NetherlandsHangzhou Huibo Science and Technology Co. Ltd., Xinjie Science Park, Hangzhou, ChinaDepartment of Implantology, Hangzhou Stomatology Hospital, Hangzhou, ChinaSavid School of Stomatology, Hangzhou Medical College, Hangzhou, ChinaDepartment of Implantology, Hangzhou Stomatology Hospital, Hangzhou, ChinaDepartment of Stomatology, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam, NetherlandsHangzhou Huibo Science and Technology Co. Ltd., Xinjie Science Park, Hangzhou, ChinaDepartment of Preventive Dental Sciences, College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaDepartment of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam, NetherlandsDepartment of Stomatology, Zhejiang Hospital, Hangzhou, ChinaDepartment of Prosthetic Dental Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam, NetherlandsDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam, NetherlandsThe repair of large-volume bone defects (LVBDs) remains a great challenge in the fields of orthopedics and maxillofacial surgery. Most clinically available bone-defect-filling materials lack proper degradability and efficient osteoinductivity. In this study, we synthesized a novel biomimetically-precipitated nanocrystalline calcium phosphate (BpNcCaP) with internally incorporated bone morphogenetic protein-2 (BpNcCaP + BMP-2) with an aim to develop properly degradable and highly osteoinductive granules to repair LVBDs. We first characterized the physicochemical properties of the granules with different incorporation amounts of BMP-2 using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We evaluated the cytotoxicity and cytocompatibility of BpNcCaP by assessing the viability and adhesion of MC3T3-E1 pre-osteoblasts using PrestoBlue assay, Rhodamine-Phalloidin and DAPI staining, respectively. We further assessed the in-vivo osteoinductive efficacy in a subcutaneous bone induction model in rats. In-vitro characterization data showed that the BpNcCaP + BMP-2 granules were comprised of hexagonal hydroxyapatite with an average crystallite size ranging from 19.7 to 25.1 nm and a grain size at 84.13 ± 28.46 nm. The vickers hardness of BpNcCaP was 32.50 ± 3.58 HV 0.025. BpNcCaP showed no obvious cytotoxicity and was favorable for the adhesion of pre-osteoblasts. BMP-2 incorporation rate could be as high as 65.04 ± 6.01%. In-vivo histomorphometric analysis showed that the volume of new bone induced by BpNcCaP exhibited a BMP-2 amount-dependent increasing manner. The BpNcCaP+50 μg BMP-2 exhibited significantly more degradation and fewer foreign body giant cells in comparison with BpNcCaP. These data suggested a promising application potential of BpNcCaP + BMP-2 in repairing LVBDs.https://www.frontiersin.org/articles/10.3389/fbioe.2022.920696/fullnanocrystallinehydroxyapatitebone morphogenetic protein-2biomimeticbone regeneration |
| spellingShingle | Gaoli Xu Gaoli Xu Chenxi Shen Chenxi Shen Haiyan Lin Haiyan Lin Jian Zhou Ting Wang Ben Wan Ben Wan Munerah Binshabaib Tymour Forouzanfar Guochao Xu Nawal Alharbi Gang Wu Gang Wu Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2 Frontiers in Bioengineering and Biotechnology nanocrystalline hydroxyapatite bone morphogenetic protein-2 biomimetic bone regeneration |
| title | Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2 |
| title_full | Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2 |
| title_fullStr | Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2 |
| title_full_unstemmed | Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2 |
| title_short | Development, In-Vitro Characterization and In-Vivo Osteoinductive Efficacy of a Novel Biomimetically-Precipitated Nanocrystalline Calcium Phosphate With Internally-Incorporated Bone Morphogenetic Protein-2 |
| title_sort | development in vitro characterization and in vivo osteoinductive efficacy of a novel biomimetically precipitated nanocrystalline calcium phosphate with internally incorporated bone morphogenetic protein 2 |
| topic | nanocrystalline hydroxyapatite bone morphogenetic protein-2 biomimetic bone regeneration |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.920696/full |
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