Biphasic calcium phosphate (BCP) materials are widely employed as bone substitute materials due to their resorption/degradation properties. Inflammation after implantation of such materials represents a prerequisite for bone tissue repair and regeneration but can be also problematic if it is not only transient and if it is followed by fibrosis and scarring. Here, we modified BCP covalently with hyaluronan (HA) and heparin (Hep), glycosaminoglycans that possess anti-inflammatory properties. Beside the characterization of particle surface properties, the focus was on in vivo tissue response after subcutaneous implantation in mice. Histological analysis revealed a decrease in signs of inflammatory response to BCP when modified with either HA or Hep. Reduced vascularization after 30 days was noticed when BCP was modified with either HA or Hep with greater cellularity in all examined time points. Compared to plain BCP, expression of endothelial-related genes Flt1 and Vcam1 was higher in BCP-HA and BCP-Hep group at day 30. Expression of osteogenesis-related genes Sp7 and Bglap after 30 days was the highest in BCP group, followed by BCP-Hep, while the lowest expression was in BCP-HA group which correlates with collagen amount. Hence, coating of BCP particles with HA seems to suppress inflammatory response together with formation of new bone-like tissue, while the presence of Hep delays the onset of inflammatory response but permits osteogenesis in this subcutaneous bone-forming model. Transferring the results of this study to other coated materials intended for biomedical application may also pave the way to reduction of inflammation after their implantation.

中文翻译：

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在小鼠皮下植入模型中，组织对肝素或透明质酸共价修饰的双相磷酸钙的反应

双相磷酸钙 (BCP) 材料由于其再吸收/降解特性而被广泛用作骨替代材料。植入此类材料后的炎症是骨组织修复和再生的先决条件，但如果炎症不仅是暂时性的，并且随后出现纤维化和瘢痕形成，也可能成为问题。在这里，我们用透明质酸 (HA) 和肝素 (Hep) 共价修饰 BCP，这些糖胺聚糖具有抗炎特性。除了颗粒表面特性的表征，重点是在小鼠皮下植入后的体内组织反应。组织学分析显示，当用 HA 或 Hep 修饰时，对 BCP 的炎症反应迹象减少。当在所有检查的时间点用 HA 或 Hep 修改 BCP 时，发现 30 天后血管化减少。与普通 BCP 相比，内皮相关基因的表达Flt1和Vcam1在BCP-HA和BCP-Hep组第30天较高。成骨相关基因Sp7和Bglap在30天后BCP组表达最高，BCP-Hep次之，BCP最低表达-HA组，与胶原蛋白量相关。因此，用 HA 包覆 BCP 颗粒似乎可以抑制炎症反应以及新骨样组织的形成，而 Hep 的存在延迟了炎症反应的发生，但在这种皮下骨形成模型中允许成骨。将这项研究的结果转移到其他用于生物医学应用的涂层材料也可能为减少植入后的炎症铺平道路。