Limelette Maxence, De Fourmestraux Claire, Despas Christelle, Lafragette Audrey, Veziers Joelle, Le Guennec Yohan, Touzot-Jourde Gwenola, Lefevre François-Xavier, Verron Elise, Bouler Jean-Michel, Bujoli Bruno, Gauthier Olivier
CNRS, CEISAM, UMR 6230, Nantes Université, 44000 Nantes, France.
Graftys SA, Eiffel Park, Pôle d'activités d'Aix en Provence, 13080 Aix en Provence, France.
J Funct Biomater. 2023 Apr 7;14(4):204. doi: 10.3390/jfb14040204.
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.
将一种商用磷酸钙（Graftys HBS）的固相与用柠檬酸钠或肝素钠稳定的绵羊或人类血液相结合。血液的存在使骨水泥的凝固反应延迟了约7 - 15小时，这取决于血液和血液稳定剂的性质。发现这种现象与HBS固相的颗粒大小直接相关，因为对后者进行长时间研磨会导致凝固时间缩短（10 - 30分钟）。尽管HBS血液复合材料硬化大约需要10小时，但与HBS对照物相比，其注射后的内聚力以及可注射性都有所提高。在HBS血液复合材料中逐渐形成了一种基于纤维蛋白的材料，大约100小时后，在晶间空间中形成了致密的三维有机网络，从而影响了复合材料的微观结构。实际上，对抛光横截面的扫描电子显微镜（SEM）分析显示，在HBS血液复合材料的整个体积中都分布着低矿物质密度区域（超过10 - 20微米）。最重要的是，当将两种骨水泥配方注射到骨髓损伤绵羊模型的胫骨软骨下松质骨中时，定量SEM分析显示HBS对照物与其与血液结合的类似物之间存在高度显著差异。植入4个月后，组织学分析清楚地表明，HBS血液复合材料发生了高度吸收（剩余骨水泥：约13.1±7.3%）和新骨形成（新形成的骨：41.8±14.7%）。这与观察到低吸收率的HBS对照物情况形成鲜明对比（剩余骨水泥：79.0±6.9%；新形成的骨：8.6±4.8%）。这项研究表明，使用血液作为HBS液相所诱导的特殊微观结构有利于植入物更快地被定植，并加速其被新形成的骨替代。因此，HBS血液复合材料可能值得被视为一种潜在适用于软骨下成形术的材料。
