Medical bone glues on the basis of calcium phosphate nanoparticles

一般来说，临床迫切需要能够有效连接骨组织的粘接剂。目前可用的医用胶水无法完成这一任务。该项目的目标是开发和合成一种基于磷酸钙的糊状物，这种糊状物能够通过胶合连接骨碎片。为了实现这一目标，将在生理环境中研究浆糊本身和骨骼的特性。这种浆糊是基于合成制备的磷酸钙纳米颗粒，经过化学修饰，允许内部交联，并与骨组织有很强的附着力。最后，我们将得到一种粘合剂，它在潮湿的骨骼环境中具有机械稳定性，生物可降解，并且可以在中等负载的缺陷中连接骨碎片。胶水不能堵塞两块骨碎片之间的接触区域，因为这将阻止它们最终通过形成新骨而连接在一起。胶水将持续约3个月，直到骨骼生物连接和愈合。首先，磷酸钙纳米颗粒以不同的方式被表面功能化。它们的生物力学性能以糊状的形式进行评估。同时进行了人类细胞系和原代细胞的生物相容性试验。最后，评估了磷酸钙纳米颗粒对骨吸收、骨生成和血管生成的影响。最后，对磷酸钙纳米颗粒进行体内测试，并在粘合实验中评估骨愈合/稳定性。目标是通过无毒性降解产物和抑制骨愈合的破骨细胞获得合适的降解特征。

In general, there is an urgent clinical demand for adhesives that are able to effectively connect bone tissue. The currently available medical glues are not able to fulfil this task. The goal of this project is the development and synthesis of a paste based on calcium phosphate which is able to join bone fragments by gluing. To achieve this, the properties of the paste itself and together with bone will be investigated in a physiological environment. The paste is based on synthetically prepared calcium phosphate nanoparticles which are chemically modified to permit am internal cross-linking and a strong adhesion to bone tissue. At the end, we will have an adhesive that is mechanically stable in the moist bone environment, biologically degradable, and can join bone fragments in a moderately loaded defect. The glue must not block the contact area between two bone fragments because this would prevent their final joining by the formation of new bone. The glue shall last for about 3 months until the bone has biologically joined and healed.First, the calcium phosphate nanoparticles are surface-functionalized in different ways. Their biomechanical properties are assessed in the form of a paste. Accompanying biocompatibility tests with human cell lines and primary cells are performed. Finally, the effect of the calcium phosphate nanoparticles on bone resorption, bone generation, and angiogenesis is assessed. Finally, the calcium phosphate nanoparticles are tested in-vivo and the bone healing/stability are assessed in a gluing experiment. A goal is also a suitable degradation profile by osteoclasts without toxic degradation products and containment of the bone healing.