Effect of a bioactive rapidly resorbing silica containing calcium alkaliphosphate bone grafting material on osteo-, angiogenesis and micromechanic bone properties in biopsies 6 months after sinus floor augmentation as compared to tricalcium phosphate and

在过去的几十年里，人们越来越多地在种植牙科中寻找合适的骨移植材料，用于窦底增强和牙槽骨隆起。然而，对于大多数临床可用的骨移植材料，能够提供这些材料的细胞和组织反应的详细特征的数据，包括来自具有临床代表性的大型动物模型和临床研究的数据，是极其稀少的。理想的骨移植材料应该具有高度的生物活性，在促进成骨的同时，还能迅速吸收，从而促进大量、快速的骨形成和骨再生，从而促进功能完整的骨组织的形成，进而促进种植体的早期植入和较短的治疗时间。因此，DFG以前资助的一个项目成功地开发了一种含有碱性磷酸钙(Si-CAOP)的高生物活性二氧化硅(Si-CAOP)骨移植材料，并在临床代表性大型动物模型和体外实验中展示了与磷酸三钙(TCP)相比，更大的骨形成和生物降解性以及对成骨的更大刺激作用。当使用TCP进行SFA时，获得了较高的临床成功率。然而，在人类身上，TCP在1-2年内就会吸收。由于Si-CAOP已被FDA批准，并根据先前资助的DFG项目中产生的数据获得CE标志，因此，拟议的项目旨在确认Si-CAOP在人体组织中具有优异的成骨特性，以及与TCP相比对骨形成的更大促进作用，从而成功地转化到临床领域。为此，将建立信号转导数据以及在大型动物绵羊研究背景下产生的数据与通过分析患者活检和放射数据获得的数据之间的相关性，以促进在患者中基于证据的使用Si-CAOP(基于可靠的综合数据集)。因此，在植入SFA 6个月后的30名患者的活检组织中，利用综合的、尖端的硬组织组织学、免疫组织化学、同步显微断层扫描和微机械分析，将Si-CAOP对成骨和血管生成的影响进行表征。这是在锥束CT数据的基础上评估移植区域的体积稳定性之外的。因此，这项拟议的项目旨在验证这样一个假设，即先前在体外和体内证明的优越的成骨特性也将导致使用Si-CAOP治疗SFA时显著促进患者组织的骨形成，而不是使用TCP。如果这一假设得到证实，在SFA后4个月而不是6个月后更早植入种植体是合乎伦理学的。

Over the last few decades there has been an ever increasing search for adequate bone grafting materials in implant dentistry for use for sinus floor augmentation (SFA) and alveolar ridge augmentation. For most clinically available bone grafting materials, however, data which would provide a detailed characterization of the cell and tissue responses to these materials including data derived from clinically representative large animal models and clinical studies are extremely scarce. An ideal bone grafting material should be highly bioactive and stimulate osteogenesis, while resorbing rapidly at the same time, thereby facilitating copious and expeditious bone formation and bone regeneration with fully functional bone, which then in its turn facilitates earlier implant placement and shorter treatment durations. As a result, a former DFG funded project succeeded in developing a highly bioactive silica containing calcium alkali orthophosphate (Si-CAOP) bone grafting material and in demonstrating greater bone formation and biodegradability as well as a greater stimulatory effect on osteogenesis, when compared to tricalcium phosphate (TCP), in the context of a clinically representative large animal model and in vitro. When using TCP for SFA, high clinical success rates were achieved. TCP, however, resorbs within 1-2 years in humans. Since Si-CAOP was cleared by the FDA and received the CE mark on the basis of the data generated in the previously funded DFG projects, the proposed project aims at confirming the excellent osteogenic properties of Si-CAOP and greater stimulatory effect on bone formation when compared to TCP, which were demonstrated in the context of these previous projects, in human tissue, so as to obtain successful translation into the clinical arena. To this end, the correlation between the signal transduction data as well as the data generated in the context of the large animal sheep study and data obtained by analyzing patient biopsies and radiological data will be established in order to facilitate the evidence-based use of Si-CAOP in patients (on the basis of robust comprehensive data sets). As a result, the effect of Si-CAOP on osteogenesis and angiogenesis will be characterized in biopsies obtained from 30 patients 6 months after SFA at implant placement, and compared to that of TCP, utilizing comprehensive, cutting-edge hard tissue histologic, immunohistochemical and synchrotronmicrotomographic and micromechanic analyses. This is in addition to evaluating the volume stability of the grafted region on the basis of cone beam CT data. Hence, the proposed project aims at testing the hypothesis that the superior osteogenic properties, which were previously demonstrated in vitro and in vivo, will also result in markedly enhanced bone formation in patient tissue when using Si-CAOP for SFA as compared to TCP. If this hypothesis will be confirmed, earlier implant placement after 4 instead of 6 months after SFA can be justified ethically.