Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing

Mozhgan Keshavarz; Parvin Alizadeh; Firoz Babu Kadumudi; Gorka Orive; Akhilesh K. Gaharwar; Miguel Castilho; Nasim Golafshan; Alireza Dolatshahi-Pirouz

doi:10.1021/acsami.3c01717

Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing

Mozhgan Keshavarz, Parvin Alizadeh (Corresponding author), Firoz Babu Kadumudi, Gorka Orive (Corresponding author), Akhilesh K. Gaharwar, Miguel Castilho, Nasim Golafshan, Alireza Dolatshahi-Pirouz (Corresponding author)

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Abstract

Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.

Original language	English
Pages (from-to)	21476-21495
Number of pages	20
Journal	ACS Applied Materials and Interfaces
Volume	15
Issue number	17
DOIs	https://doi.org/10.1021/acsami.3c01717
Publication status	Published - 3 May 2023

Bibliographical note

Funding Information:
P.A. wishes to thank the Iranian Ministry of Science and the PhD funding support from Tarbiat Modares University of Tehran. This work has also received funding from the Iran National Science Foundation (INSF) Collaboration Grants Scheme Iran (ref no.: 97014136). M.K. thanks to the Tarbiat Modares University of Tehran for the PhD grant and the University of the Basque Country and Technical University of Denmark for hosting her during the secondment. A.D.-P. would like to acknowledge the Danish Council for Independent Research (Technology and Production Sciences, 8105-00003B) and the VIDI research programme with project number R0004387, which is (partly) financed by The Netherlands Organisation for Scientific Research (NWO). This work has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 951747. M.C. would like to acknowledge the financial support from The Netherlands Organization for Scientific Research with the project number OCENW.XS5.161 and the Gravitation Program “Materials Driven Regeneration”, project number 024.003.013. This work has also supported by the Spanish Ministry of Economy, Industry, and Competitiveness (PID2019-106094RB-I00/AEI/10.13039/501100011033) and technical assistance from the (Drug Formulation Unit, U10) at the University of the Basque Country.

Keywords

alginate
bio glass
hydrogels
laponite
mesenchymal stem cells
nanomaterials
nanosilicate

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Cite this

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title = "Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing",

abstract = "Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.",

keywords = "alginate, bio glass, hydrogels, laponite, mesenchymal stem cells, nanomaterials, nanosilicate",

author = "Mozhgan Keshavarz and Parvin Alizadeh and Kadumudi, {Firoz Babu} and Gorka Orive and Gaharwar, {Akhilesh K.} and Miguel Castilho and Nasim Golafshan and Alireza Dolatshahi-Pirouz",

note = "Funding Information: P.A. wishes to thank the Iranian Ministry of Science and the PhD funding support from Tarbiat Modares University of Tehran. This work has also received funding from the Iran National Science Foundation (INSF) Collaboration Grants Scheme Iran (ref no.: 97014136). M.K. thanks to the Tarbiat Modares University of Tehran for the PhD grant and the University of the Basque Country and Technical University of Denmark for hosting her during the secondment. A.D.-P. would like to acknowledge the Danish Council for Independent Research (Technology and Production Sciences, 8105-00003B) and the VIDI research programme with project number R0004387, which is (partly) financed by The Netherlands Organisation for Scientific Research (NWO). This work has also received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement no. 951747. M.C. would like to acknowledge the financial support from The Netherlands Organization for Scientific Research with the project number OCENW.XS5.161 and the Gravitation Program “Materials Driven Regeneration”, project number 024.003.013. This work has also supported by the Spanish Ministry of Economy, Industry, and Competitiveness (PID2019-106094RB-I00/AEI/10.13039/501100011033) and technical assistance from the (Drug Formulation Unit, U10) at the University of the Basque Country. ",

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AU - Keshavarz, Mozhgan

AU - Alizadeh, Parvin

AU - Kadumudi, Firoz Babu

AU - Orive, Gorka

AU - Gaharwar, Akhilesh K.

AU - Castilho, Miguel

AU - Golafshan, Nasim

AU - Dolatshahi-Pirouz, Alireza

N1 - Funding Information: P.A. wishes to thank the Iranian Ministry of Science and the PhD funding support from Tarbiat Modares University of Tehran. This work has also received funding from the Iran National Science Foundation (INSF) Collaboration Grants Scheme Iran (ref no.: 97014136). M.K. thanks to the Tarbiat Modares University of Tehran for the PhD grant and the University of the Basque Country and Technical University of Denmark for hosting her during the secondment. A.D.-P. would like to acknowledge the Danish Council for Independent Research (Technology and Production Sciences, 8105-00003B) and the VIDI research programme with project number R0004387, which is (partly) financed by The Netherlands Organisation for Scientific Research (NWO). This work has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 951747. M.C. would like to acknowledge the financial support from The Netherlands Organization for Scientific Research with the project number OCENW.XS5.161 and the Gravitation Program “Materials Driven Regeneration”, project number 024.003.013. This work has also supported by the Spanish Ministry of Economy, Industry, and Competitiveness (PID2019-106094RB-I00/AEI/10.13039/501100011033) and technical assistance from the (Drug Formulation Unit, U10) at the University of the Basque Country.

PY - 2023/5/3

Y1 - 2023/5/3

N2 - Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.

AB - Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.

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KW - hydrogels

KW - laponite

KW - mesenchymal stem cells

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Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing

Abstract

Bibliographical note

Keywords

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