Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair

Jietao Xu; Jana Vecstaudza; Marinus A. Wesdorp; Margot Labberté; Nicole Kops; Manuela Salerno; Joeri Kok; Marina Simon; Marie-Françoise Harmand; Karin Vancíková; Bert van Rietbergen; Massimiliano Maraglino Misciagna; Laura Dolcini; Giuseppe Filardo; Eric Farrell; Gerjo J.V.M. van Osch; Janis Locs; Pieter A.J. Brama

doi:10.1016/j.mtbio.2024.100959

Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair

Jietao Xu, Jana Vecstaudza, Marinus A. Wesdorp, Margot Labberté, Nicole Kops, Manuela Salerno, Joeri Kok, Marina Simon, Marie-Françoise Harmand, Karin Vancíková, Bert van Rietbergen, Massimiliano Maraglino Misciagna, Laura Dolcini, Giuseppe Filardo, Eric Farrell, Gerjo J.V.M. van Osch, Janis Locs (Corresponding author), Pieter A.J. Brama (Corresponding author)

Orthopaedic Biomechanics

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Abstract

Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 μm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

Original language	English
Article number	100959
Number of pages	15
Journal	Materials Today Bio
Volume	25
DOIs	https://doi.org/10.1016/j.mtbio.2024.100959
Publication status	Published - Apr 2024

Funding

This work was supported by the European Union's Horizon 2020 research and innovation programme [grant numbers EURONANOMED2017-077 ]; Science Foundation of Ireland [grant Number SFI /16/ENM- ERA /3458]; Ministero della Salute ( IMH ); Stated Education Development Agency SEDA /VIAA; Technology Foundation ( STW ). The authors acknowledge financial support from the European Union's Horizon 2020 research and innovation programme under the grant agreement No. 857287 (BBCE – Baltic Biomaterials Centre of Excellence).

Funders	Funder number
Institute of Mental Hygiene
Science Foundation Ireland - SFI	SFI /16/ENM- ERA /3458
Stichting voor de Technische Wetenschappen	857287
Horizon 2020	EURONANOMED2017-077
State Education Development Agency Republic of Latvia	SEDA /VIAA

Keywords

Amorphous calcium phosphate
Osteochondral defect
Regenerative medicine
Strontium
Tissue engineering

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Xu, J., Vecstaudza, J., Wesdorp, M. A., Labberté, M., Kops, N., Salerno, M., Kok, J., Simon, M., Harmand, M.-F., Vancíková, K., van Rietbergen, B., Misciagna, M. M., Dolcini, L., Filardo, G., Farrell, E., van Osch, G. J. V. M., Locs, J., & Brama, P. A. J. (2024). Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair. Materials Today Bio, 25, Article 100959. https://doi.org/10.1016/j.mtbio.2024.100959

@article{65a8ad2a9011439182157fcb25a0784a,

title = "Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair",

abstract = "Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 μm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair. ",

keywords = "Amorphous calcium phosphate, Osteochondral defect, Regenerative medicine, Strontium, Tissue engineering",

author = "Jietao Xu and Jana Vecstaudza and Wesdorp, {Marinus A.} and Margot Labbert{\'e} and Nicole Kops and Manuela Salerno and Joeri Kok and Marina Simon and Marie-Fran{\c c}oise Harmand and Karin Vanc{\'i}kov{\'a} and {van Rietbergen}, Bert and Misciagna, {Massimiliano Maraglino} and Laura Dolcini and Giuseppe Filardo and Eric Farrell and {van Osch}, {Gerjo J.V.M.} and Janis Locs and Brama, {Pieter A.J.}",

year = "2024",

month = apr,

doi = "10.1016/j.mtbio.2024.100959",

language = "English",

volume = "25",

journal = "Materials Today Bio",

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Xu, J, Vecstaudza, J, Wesdorp, MA, Labberté, M, Kops, N, Salerno, M, Kok, J, Simon, M, Harmand, M-F, Vancíková, K, van Rietbergen, B, Misciagna, MM, Dolcini, L, Filardo, G, Farrell, E, van Osch, GJVM, Locs, J & Brama, PAJ 2024, 'Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair', Materials Today Bio, vol. 25, 100959. https://doi.org/10.1016/j.mtbio.2024.100959

TY - JOUR

T1 - Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair

AU - Xu, Jietao

AU - Vecstaudza, Jana

AU - Wesdorp, Marinus A.

AU - Labberté, Margot

AU - Kops, Nicole

AU - Salerno, Manuela

AU - Kok, Joeri

AU - Simon, Marina

AU - Harmand, Marie-Françoise

AU - Vancíková, Karin

AU - van Rietbergen, Bert

AU - Misciagna, Massimiliano Maraglino

AU - Dolcini, Laura

AU - Filardo, Giuseppe

AU - Farrell, Eric

AU - van Osch, Gerjo J.V.M.

AU - Locs, Janis

AU - Brama, Pieter A.J.

PY - 2024/4

Y1 - 2024/4

N2 - Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 μm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

AB - Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 μm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

KW - Amorphous calcium phosphate

KW - Osteochondral defect

KW - Regenerative medicine

KW - Strontium

KW - Tissue engineering

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DO - 10.1016/j.mtbio.2024.100959

M3 - Article

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SN - 2590-0064

VL - 25

JO - Materials Today Bio

JF - Materials Today Bio

M1 - 100959

ER -

Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair

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