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

April 07, 2023

Maxence Limelette (1) (2), Claire De Fourmestraux (3) (4), Christelle Despas (5), Audrey Lefragette (3), Joelle Veziers (4), Yohan Le Guennec (4), Gwenola Touzot-Jourde (3) (4), Francois-Xavier Lefevre (1), Elise Verron (1), Jean-Michel Bouler (1), Bruno Bujoli (1), Olivier Gauthier (3) (4)
Journal of Functional Biomaterials. Volume 14, Issue 4 (7 April 2023). DOI:


Calcium phosphate cement, blood-containing injectable bone substitute, bone marrow lesion, bone reconstruction


The solid phase of a commercial calcium phosphate (Graftys® 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.

How Our Software Was Used

Quantitative analyses were performed with DragonFly using the deep learning module for realistic and accurate quantification of bone tissue.

Author Affiliation

(1) CNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, France
(2) Graftys SA, Eiffel Park, Pôle d’activités d’Aix en Provence, 13080 Aix en Provence, France
(3) Department of Small Animal and Equine Surgery and Anesthesia, Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (ONIRIS), 44307 Nantes, France
(4) Regenerative Medicine and Skeleton, INSERM, University Hospital (CHU), UMR 1229-RMeS, Nantes University, 44000 Nantes, France
(5) LCPME, CNRS UMR 7564, Université de Lorraine, 54800 Villers Lès Nancy, France