PDF(Pubmed)
Abstract：
The incorporation of bioactive ions into biomaterials has gained significant attention as a strategy to enhance bone tissue regeneration on the molecular level. However, little knowledge exists about the effects of the addition of these ions on the immune response and especially on the most important cellular regulators, the macrophages. Thus, this study aimed to investigate the in vitro cytocompatibility and in vivo regulation of bone remodeling and material-related immune responses of a biphasic bone substitute (BBS) coated with metal ions (Sr2+/Mg2+) and PLGA, using the pure BBS as control group. Initially, two cytocompatible modified material variants were identified according to the in vitro results obtained following the DIN EN ISO 10993-5 protocol. The surface structure and ion release of both materials were characterized using SEM-EDX and ICP-OES. The materials were then implanted into Wistar rats for 10, 30, and 90 days using a cranial defect model. Histopathological and histomorphometrical analyses were applied to evaluate material degradation, bone regeneration, osteoconductivity, and immune response. The findings revealed that in all study groups comparable new bone formation were found. However, during the early implantation period, the BBS_Sr2+ group exhibited significantly faster regeneration compared to the other two groups. Additionally, all materials induced comparable tissue and immune responses involving high numbers of both pro-inflammatory macrophages and multinucleated giant cells (MNGCs). In conclusion, this study delved into the repercussions of therapeutic ion doping on bone regeneration patterns and inflammatory responses, offering insights for the advancement of a new generation of biphasic calcium phosphate materials with potential clinical applicability.
摘要：
将生物活性离子掺入生物材料中作为在分子水平上增强骨组织再生的策略已经获得了极大的关注。然而,关于添加这些离子对免疫反应的影响，尤其是对最重要的细胞调节剂的影响，巨噬细胞。因此，本研究旨在研究涂覆有金属离子（Sr2/Mg2）和PLGA的双相骨替代物（BBS）的体外细胞相容性和体内骨重建和材料相关免疫反应的调节，以纯BBS为对照组。最初，根据根据DINENISO10993-5方案获得的体外结果鉴定了两种细胞相容性修饰的材料变体。使用SEM-EDX和ICP-OES表征了两种材料的表面结构和离子释放。然后使用颅骨缺损模型将材料植入Wistar大鼠10、30和90天。组织病理学和组织形态学分析用于评估材料降解，骨再生,骨传导性,和免疫反应。研究结果表明，在所有研究组中都发现了类似的新骨形成。然而,在植入早期，与其他两组相比，BBS_Sr2组的再生速度明显加快。此外,所有材料均可诱导类似的组织和免疫反应,包括大量促炎巨噬细胞和多核巨细胞(MNGC).总之,这项研究探讨了治疗性离子掺杂对骨再生模式和炎症反应的影响，为具有潜在临床适用性的新一代双相磷酸钙材料的发展提供见解。
