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Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models

View ORCID ProfileBregje W.M de Wildt, Robin van der Meijden, Paul A.A. Bartels, Nico A.J.M. Sommerdijk, Anat Akiva, Keita Ito, View ORCID ProfileSandra Hofmann
doi: https://doi.org/10.1101/2022.06.17.496534
Bregje W.M de Wildt
1Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
4Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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Robin van der Meijden
2Dept of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6525 GA Nijmegen, The Netherlands
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Paul A.A. Bartels
3Biomedical Materials and Chemistry, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
4Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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Nico A.J.M. Sommerdijk
2Dept of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6525 GA Nijmegen, The Netherlands
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Anat Akiva
2Dept of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, 6525 GA Nijmegen, The Netherlands
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Keita Ito
1Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
4Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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Sandra Hofmann
1Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
4Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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  • For correspondence: s.hofmann@tue.nl
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Abstract

Human in vitro bone models can create the possibility for investigation of physiological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3R). Current in vitro models lack cell-matrix interactions and their spatiotemporal complexity. To facilitate these analyses, a bone-mimetic template was developed in this study, inspired by bone’s extracellular matrix composition and organization. Silk fibroin (SF) was used as an organic matrix, poly-aspartic acid (pAsp) was used to mimic the functionality of non-collagenous proteins, and 10x simulated body fluid served as mineralization solution. By using pAsp in the mineralization solution, minerals were guided towards the SF material resulting in mineralization inside and as a coating on top of the SF. After cytocompatibility testing, remodeling experiments were performed in which mineralized scaffold remodeling by osteoclasts and osteoblasts was tracked with non-destructive micro-computed tomography and medium analyses over a period of 42 days. The mineralized scaffolds supported osteoclastic resorption and osteoblastic mineralization, in the physiological bone remodeling specific sequence. This model could therefore facilitate the investigation of cell-matrix interactions and may thus reduce animal experiments and advance in vitro drug testing for bone remodeling pathologies like osteoporosis, where cell-matrix interactions need to be targeted.

Competing Interest Statement

The authors have declared no competing interest.

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Posted June 17, 2022.
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Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models
Bregje W.M de Wildt, Robin van der Meijden, Paul A.A. Bartels, Nico A.J.M. Sommerdijk, Anat Akiva, Keita Ito, Sandra Hofmann
bioRxiv 2022.06.17.496534; doi: https://doi.org/10.1101/2022.06.17.496534
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Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models
Bregje W.M de Wildt, Robin van der Meijden, Paul A.A. Bartels, Nico A.J.M. Sommerdijk, Anat Akiva, Keita Ito, Sandra Hofmann
bioRxiv 2022.06.17.496534; doi: https://doi.org/10.1101/2022.06.17.496534

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