Acceleration of Bone Regeneration Induced by a Soft-Callus Mimetic Material

Alessia Longoni; Lizette Utomo; Abbie Robinson; Riccardo Levato; Antoine J W P Rosenberg; Debby Gawlitta

doi:10.1002/advs.202103284

Acceleration of Bone Regeneration Induced by a Soft-Callus Mimetic Material

Alessia Longoni, Lizette Utomo, Abbie Robinson, Riccardo Levato, Antoine J W P Rosenberg, Debby Gawlitta

Utrecht University, University Medical Center Utrecht

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Clinical implementation of endochondral bone regeneration (EBR) would benefit from the engineering of devitalized cartilaginous constructs of allogeneic origins. Nevertheless, development of effective devitalization strategies that preserves extracellular matrix (ECM) is still challenging. The aim of this study is to investigate EBR induced by devitalized, soft callus-mimetic spheroids. To challenge the translatability of this approach, the constructs are generated using an allogeneic cell source. Neo-bone formation is evaluated in an immunocompetent rat model, subcutaneously and in a critical size femur defect. Living spheroids are used as controls. Also, the effect of spheroid maturation towards hypertrophy is evaluated. The devitalization procedure successfully induces cell death without affecting ECM composition or bioactivity. In vivo, a larger amount of neo-bone formation is observed for the devitalized chondrogenic group both ectopically and orthotopically. In the femur defect, accelerated bone regeneration is observed in the devitalized chondrogenic group, where defect bridging is observed 4 weeks post-implantation. The authors' results show, for the first time, a dramatic increase in the rate of bone formation induced by devitalized soft callus-mimetics. These findings pave the way for the development of a new generation of allogeneic, "off-the-shelf" products for EBR, which are suitable for the treatment of every patient.

Original language	English
Article number	2103284
Pages (from-to)	1-14
Journal	Advanced Science
Volume	9
Issue number	6
Early online date	28 Dec 2021
DOIs	https://doi.org/10.1002/advs.202103284
Publication status	Published - 24 Feb 2022

Bibliographical note

Funding Information:
Project no. S‐16‐130G was supported by the AO Foundation. The antibody against collagen type II (II‐II6B3), developed by T. F. Linsenmayer, was obtained from the DSHB developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA52242. R.L. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 949806). Finally, the authors would like to thank Anja van der Sar for her gracious support during the animal experiments.

Funding Information:
Project no. S-16-130G was supported by the AO Foundation. The antibody against collagen type II (II-II6B3), developed by T. F. Linsenmayer, was obtained from the DSHB developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA52242. R.L. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 949806). Finally, the authors would like to thank Anja van der Sar for her gracious support during the animal experiments.

Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Keywords

allogeneic
devitalization
endochondral bone tissue regeneration
mesenchymal stromal cells
orthotopic bone defect

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Advanced Science - 2022 - Longoni - Acceleration of Bone Regeneration Induced by a Soft‐Callus Mimetic MaterialFinal published version, 5.25 MBLicence: CC BY

Cite this

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title = "Acceleration of Bone Regeneration Induced by a Soft-Callus Mimetic Material",

abstract = "Clinical implementation of endochondral bone regeneration (EBR) would benefit from the engineering of devitalized cartilaginous constructs of allogeneic origins. Nevertheless, development of effective devitalization strategies that preserves extracellular matrix (ECM) is still challenging. The aim of this study is to investigate EBR induced by devitalized, soft callus-mimetic spheroids. To challenge the translatability of this approach, the constructs are generated using an allogeneic cell source. Neo-bone formation is evaluated in an immunocompetent rat model, subcutaneously and in a critical size femur defect. Living spheroids are used as controls. Also, the effect of spheroid maturation towards hypertrophy is evaluated. The devitalization procedure successfully induces cell death without affecting ECM composition or bioactivity. In vivo, a larger amount of neo-bone formation is observed for the devitalized chondrogenic group both ectopically and orthotopically. In the femur defect, accelerated bone regeneration is observed in the devitalized chondrogenic group, where defect bridging is observed 4 weeks post-implantation. The authors' results show, for the first time, a dramatic increase in the rate of bone formation induced by devitalized soft callus-mimetics. These findings pave the way for the development of a new generation of allogeneic, {"}off-the-shelf{"} products for EBR, which are suitable for the treatment of every patient.",

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author = "Alessia Longoni and Lizette Utomo and Abbie Robinson and Riccardo Levato and Rosenberg, {Antoine J W P} and Debby Gawlitta",

note = "Funding Information: Project no. S‐16‐130G was supported by the AO Foundation. The antibody against collagen type II (II‐II6B3), developed by T. F. Linsenmayer, was obtained from the DSHB developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA52242. R.L. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 949806). Finally, the authors would like to thank Anja van der Sar for her gracious support during the animal experiments. Funding Information: Project no. S-16-130G was supported by the AO Foundation. The antibody against collagen type II (II-II6B3), developed by T. F. Linsenmayer, was obtained from the DSHB developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA52242. R.L. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 949806). Finally, the authors would like to thank Anja van der Sar for her gracious support during the animal experiments. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH",

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Acceleration of Bone Regeneration Induced by a Soft-Callus Mimetic Material

Abstract

Bibliographical note

Keywords

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