Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions

The solid phase of a commercial calcium phosphate (Graftys<sup>®</sup> HBS) was combined with ovine or human blood stabilized either with sodium citrate or sodium heparin. The presence of blood delayed the setting reaction of the cement by ca. 7–15 h, depending on the nature of the blood...

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Main Authors: Maxence Limelette, Claire De Fourmestraux, Christelle Despas, Audrey Lafragette, Joelle Veziers, Yohan Le Guennec, Gwenola Touzot-Jourde, François-Xavier Lefevre, Elise Verron, Jean-Michel Bouler, Bruno Bujoli, Olivier Gauthier
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Journal of Functional Biomaterials
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Online Access:https://www.mdpi.com/2079-4983/14/4/204
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author Maxence Limelette
Claire De Fourmestraux
Christelle Despas
Audrey Lafragette
Joelle Veziers
Yohan Le Guennec
Gwenola Touzot-Jourde
François-Xavier Lefevre
Elise Verron
Jean-Michel Bouler
Bruno Bujoli
Olivier Gauthier
author_facet Maxence Limelette
Claire De Fourmestraux
Christelle Despas
Audrey Lafragette
Joelle Veziers
Yohan Le Guennec
Gwenola Touzot-Jourde
François-Xavier Lefevre
Elise Verron
Jean-Michel Bouler
Bruno Bujoli
Olivier Gauthier
author_sort Maxence Limelette
collection DOAJ
description The solid phase of a commercial calcium phosphate (Graftys<sup>®</sup> HBS) was combined with ovine or human blood stabilized either with sodium citrate or sodium heparin. The presence of blood delayed the setting reaction of the cement by ca. 7–15 h, depending on the nature of the blood and blood stabilizer. This phenomenon was found to be directly related to the particle size of the HBS solid phase, since prolonged grinding of the latter resulted in a shortened setting time (10–30 min). Even though ca. 10 h were necessary for the HBS blood composite to harden, its cohesion right after injection was improved when compared to the HBS reference as well as its injectability. A fibrin-based material was gradually formed in the HBS blood composite to end-up, after ca. 100 h, with a dense 3D organic network present in the intergranular space, thus affecting the microstructure of the composite. Indeed, SEM analyses of polished cross-sections showed areas of low mineral density (over 10–20 µm) spread in the whole volume of the HBS blood composite. Most importantly, when the two cement formulations were injected in the tibial subchondral cancellous bone in a bone marrow lesion ovine model, quantitative SEM analyses showed a highly significant difference between the HBS reference versus its analogue combined with blood. After a 4-month implantation, histological analyses clearly showed that the HBS blood composite underwent high resorption (remaining cement: ca. 13.1 ± 7.3%) and new bone formation (newly formed bone: 41.8 ± 14.7%). This was in sharp contrast with the case of the HBS reference for which a low resorption rate was observed (remaining cement: 79.0 ± 6.9%; newly formed bone: 8.6 ± 4.8%). This study suggested that the particular microstructure, induced by the use of blood as the HBS liquid phase, favored quicker colonization of the implant and acceleration of its replacement by newly formed bone. For this reason, the HBS blood composite might be worth considering as a potentially suitable material for subchondroplasty.
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spelling doaj.art-71edf94b1d8d4ebdb8a9c01fac2738532023-11-17T19:53:10ZengMDPI AGJournal of Functional Biomaterials2079-49832023-04-0114420410.3390/jfb14040204Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow LesionsMaxence Limelette0Claire De Fourmestraux1Christelle Despas2Audrey Lafragette3Joelle Veziers4Yohan Le Guennec5Gwenola Touzot-Jourde6François-Xavier Lefevre7Elise Verron8Jean-Michel Bouler9Bruno Bujoli10Olivier Gauthier11CNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, FranceDepartment of Small Animal and Equine Surgery and Anesthesia, Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (ONIRIS), 44307 Nantes, FranceLCPME, CNRS UMR 7564, Université de Lorraine, 54800 Villers Lès Nancy, FranceDepartment of Small Animal and Equine Surgery and Anesthesia, Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (ONIRIS), 44307 Nantes, FranceRegenerative Medicine and Skeleton, INSERM, University Hospital (CHU), UMR 1229-RMeS, Nantes University, 44000 Nantes, FranceRegenerative Medicine and Skeleton, INSERM, University Hospital (CHU), UMR 1229-RMeS, Nantes University, 44000 Nantes, FranceDepartment of Small Animal and Equine Surgery and Anesthesia, Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (ONIRIS), 44307 Nantes, FranceCNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, FranceCNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, FranceCNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, FranceCNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, FranceDepartment of Small Animal and Equine Surgery and Anesthesia, Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (ONIRIS), 44307 Nantes, FranceThe solid phase of a commercial calcium phosphate (Graftys<sup>®</sup> HBS) was combined with ovine or human blood stabilized either with sodium citrate or sodium heparin. The presence of blood delayed the setting reaction of the cement by ca. 7–15 h, depending on the nature of the blood and blood stabilizer. This phenomenon was found to be directly related to the particle size of the HBS solid phase, since prolonged grinding of the latter resulted in a shortened setting time (10–30 min). Even though ca. 10 h were necessary for the HBS blood composite to harden, its cohesion right after injection was improved when compared to the HBS reference as well as its injectability. A fibrin-based material was gradually formed in the HBS blood composite to end-up, after ca. 100 h, with a dense 3D organic network present in the intergranular space, thus affecting the microstructure of the composite. Indeed, SEM analyses of polished cross-sections showed areas of low mineral density (over 10–20 µm) spread in the whole volume of the HBS blood composite. Most importantly, when the two cement formulations were injected in the tibial subchondral cancellous bone in a bone marrow lesion ovine model, quantitative SEM analyses showed a highly significant difference between the HBS reference versus its analogue combined with blood. After a 4-month implantation, histological analyses clearly showed that the HBS blood composite underwent high resorption (remaining cement: ca. 13.1 ± 7.3%) and new bone formation (newly formed bone: 41.8 ± 14.7%). This was in sharp contrast with the case of the HBS reference for which a low resorption rate was observed (remaining cement: 79.0 ± 6.9%; newly formed bone: 8.6 ± 4.8%). This study suggested that the particular microstructure, induced by the use of blood as the HBS liquid phase, favored quicker colonization of the implant and acceleration of its replacement by newly formed bone. For this reason, the HBS blood composite might be worth considering as a potentially suitable material for subchondroplasty.https://www.mdpi.com/2079-4983/14/4/204calcium phosphate cementblood-containing injectable bone substitutebone marrow lesionbone reconstruction
spellingShingle Maxence Limelette
Claire De Fourmestraux
Christelle Despas
Audrey Lafragette
Joelle Veziers
Yohan Le Guennec
Gwenola Touzot-Jourde
François-Xavier Lefevre
Elise Verron
Jean-Michel Bouler
Bruno Bujoli
Olivier Gauthier
Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions
Journal of Functional Biomaterials
calcium phosphate cement
blood-containing injectable bone substitute
bone marrow lesion
bone reconstruction
title Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions
title_full Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions
title_fullStr Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions
title_full_unstemmed Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions
title_short Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions
title_sort calcium phosphate cements combined with blood as a promising tool for the treatment of bone marrow lesions
topic calcium phosphate cement
blood-containing injectable bone substitute
bone marrow lesion
bone reconstruction
url https://www.mdpi.com/2079-4983/14/4/204
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