TY - JOUR
T1 - Acceleration of Bone Regeneration Induced by a Soft-Callus Mimetic Material
AU - Longoni, Alessia
AU - Utomo, Lizette
AU - Robinson, Abbie
AU - Levato, Riccardo
AU - Rosenberg, Antoine J W P
AU - Gawlitta, Debby
N1 - 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
PY - 2022/2/24
Y1 - 2022/2/24
N2 - 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.
AB - 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.
KW - allogeneic
KW - devitalization
KW - endochondral bone tissue regeneration
KW - mesenchymal stromal cells
KW - orthotopic bone defect
UR - http://www.scopus.com/inward/record.url?scp=85122025188&partnerID=8YFLogxK
U2 - 10.1002/advs.202103284
DO - 10.1002/advs.202103284
M3 - Article
C2 - 34962103
VL - 9
SP - 1
EP - 14
JO - Advanced Science
JF - Advanced Science
IS - 6
M1 - 2103284
ER -