Electrochemically assisted deposition of trace element modified calcium and magnesium phosphate coatings on titanium for improved implant healing in osteoporotic bone

电化学辅助沉积微量元素修饰的磷酸钙和磷酸镁涂层在钛上，以改善骨质疏松骨的种植体愈合

• 批准号: 250488887
• 负责人: Professor Dr. Uwe Gbureck, since 2/2017
• 金额: --
• 依托单位: Institut für Werkstoffwissenschaft
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/250488887?language=en
• 关键词: Electrochemically; assisted; deposition; trace; element

Implants made from titanium and its alloys are well-established biomaterials and have been in use for load-bearing applications as well as for implantation into soft tissue for decades. Despite the generally good implant success rates concerning healing and retention time there is still a need for further improvements, particularly for use in more challenging situations, e.g. in the case of a weakened osseous bed caused by systemic diseases like osteoporosis. Hence the aim of this project is to further improve implant integration, specifically during the initial healing phase, by using inorganic bioactive mediators: Controlled release of the trace elements copper and zinc can stimulate vascularization, while chemotactic zinc ions recruit and stimulate osteogenic cells, and strontium release reduces osteoclastic activity. In combination, these effects are expected to increase bone formation adjacent to the modified surfaces.During the first project phase, the immobilization and controlled release of the separate trace elements could be established in calcium and magnesium phosphate coatings, namely brushite (CaHPO4 * 2H2O) and struvite (MgNH4PO4 * 6H2O), deposited on titanium substrates. The second 12-month project phase is dedicated to the fabrication and characterization of coating systems which will combine several trace elements to obtain synergetic effects of their specific biological activities.The resulting coatings will be examined regarding their physicochemical properties, namely their quantitative composition, morphology, crystallinity, as well as the distribution of the incorporated trace elements and their oxidation state. In particular, the newly available focused ion beam (FIB) technique will be combined with release studies in order to analyze the influence of the local coating composition on the release kinetics of the trace elements.For the evaluation of the angiogenetic potential both endothelial cell monocultures in 2D and 3D techniques as well as co-cultures with other cell types relevant for angiogenesis in vivo will be used. In particular the influence of the trace metal ions on the interaction of endothelial cells with monocytes and smooth muscle cells will be analyzed. Both the osteoblast activating potential of zinc and the osteoclast inhibiting activity of strontium containing coatings will be evaluated by means of colonization with an osteoblast (MG63) or an osteoclast (RAW) cell line, respectively.In a first animal study, both the effect of the strontium concentration in the coating and the effect of the coating matrix (struvite or brushite) will be examined. Utilizing the bioactive effects of the mentioned trace elements as an alternative to growth factors with comparable effects is believed to improve the performance of implants in a likewise manner, but with a higher safety margin.

由钛及其合金制成的植入物是一种成熟的生物材料，几十年来一直用于承载应用以及植入软组织。尽管在愈合和保留时间方面，植入物的成功率总体上很好，但仍需要进一步改进，特别是在更具挑战性的情况下使用，例如在骨质疏松症等全身性疾病引起的骨床弱化的情况下。因此，该项目的目的是通过使用无机生物活性介质进一步改善种植体的整合，特别是在初始愈合阶段：微量元素铜和锌的可控释放可以刺激血管化，而趋化锌离子可以招募和刺激成骨细胞，锶的释放可以降低破骨活性。综上所述，这些影响预计会增加修饰表面附近的骨形成。在第一期项目中，可以在钛基上沉积的磷酸钙镁涂层即刷石（CaHPO4 * 2H2O）和鸟粪石（MgNH4PO4 * 6H2O）中建立单独微量元素的固定和控释。第二个为期12个月的项目阶段致力于涂层系统的制造和表征，该涂层系统将结合几种微量元素以获得其特定生物活性的协同效应。所得到的涂层将检查其物理化学性质，即它们的定量组成，形态，结晶度，以及所加入的微量元素的分布及其氧化状态。特别是，新出现的聚焦离子束（FIB）技术将与释放研究相结合，以分析局部涂层成分对微量元素释放动力学的影响。为了评估血管生成潜力，将使用2D和3D技术的内皮细胞单培养以及与体内血管生成相关的其他细胞类型的共培养。特别是微量金属离子对内皮细胞与单核细胞和平滑肌细胞相互作用的影响将被分析。锌的成骨细胞激活电位和含锶涂层的破骨细胞抑制活性将分别通过成骨细胞（MG63）或破骨细胞（RAW）细胞系定植来评估。在第一个动物研究中，将检查涂层中锶浓度的影响和涂层基质（鸟粪石或刷石）的影响。利用上述微量元素的生物活性效应作为生长因子的替代品，具有类似的效果，被认为可以以同样的方式改善植入物的性能，但具有更高的安全边际。

项目成果

Osteoclast and osteoblast response to strontium-doped struvite coatings on titanium for improved bone integration

• DOI: 10.1515/bmt-2019-0265
• 发表时间: 2020-05
• 期刊: Biomedical Engineering / Biomedizinische Technik
• 作者: C. Moseke;Katharina Wimmer;M. Meininger;J. Zerweck;C. Wolf-Brandstetter;U. Gbureck;A. Ewald

Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements

• DOI: 10.1088/1748-605x/ab5d7b
• 发表时间: 2019-11
• 期刊: Biomedical Materials
• 影响因子: 4
• 作者: C. Wolf-Brandstetter;R. Beutner;R. Hess;S. Bierbaum;Katrin Wagner;D. Scharnweber;U. Gbureck;C. Moseke