Osteoclast activation by radiolytic degradation of organic/inorganic double hybrid materials (DHM) for controlled enhanced degradation of bone substitute materials

本研究项目的出发点是超临界骨缺损，必须用生物材料来治疗，以确保骨组织的完全再生。这样的生物材料受到广泛的要求，通常只能通过将不同的材料组合在复合材料中来满足。这就提出了一个问题，这些成分是如何在不同的长度尺度上排列的，也就是说，它们是否遵循骨骼模型的层次结构。这将增加使材料适应目标组织的自由度。在这样的结构下，重要的功能和性质，如机械强度、降解和可吸收性、骨细胞刺激等，可以被分离或耦合。为了满足这一系列的要求，该项目将研究双重混合材料（DHM），它对应于自然界中经常发现的“砖和砂浆”模型，因为它们由混合材料颗粒和有机基质（胶原蛋白）组成。在这种情况下，杂交颗粒由有机（胶原蛋白）和无机（二氧化硅）组分组成。该材料系统允许-通过在合成的不同阶段的胶原蛋白预处理和组分比例的选择-特异性地修改DHM的可降解性。因此，DHM可以适应骨再生，并在必要时刺激它。为此，使用伽马射线照射刺激破骨细胞物质的吸收，DHM的胶原蛋白（更准确地说是它们的成分）将被辐射分解降解预先破坏。材料系统的灵活性允许胶原蛋白在所有不同的层次结构中使用。此外，可变材料合成允许在所有水平上使用辐射处理和未处理的胶原蛋白。因此，该材料可以刺激破骨细胞，即加速可吸收性，快速脱细胞降解，同时具有高机械强度。为了能够保证即使在较大的骨缺损和相应的较大的生物材料标本的情况下也能进行这一过程，将通过基于挤压的3D绘图来增加进一步的分层水平。DHM通过膏体挤压加工成大孔支架，其中空隙相使骨细胞能够接近链表面。在这里，伽马射线照射可以改善基质胶原的粘弹性，从而通过三维绘图实现良好的加工。未来，骨替代材料的降解和吸收可能会根据骨骼状况和患者的一般情况通过预处理胶原蛋白复合材料进行调节。

Starting point for this research project are supercritical bone defects, which have to be treated with a biomaterial to ensure a complete regeneration of the bone tissue. Such biomaterials are subject to a wide range of requirements, which can often only be met by combining different materials in a composite. This raises the question of how these components are arranged on different length scales, i.e. whether they follow a hierarchical structure following the bone model. This would increase the degrees of freedom to adapt the material to the target tissue. Following such a structure, important functions and properties, such as mechanical strength, degradation and resorbability, bone cell stimulation, etc., could be either separated or coupled.In order to meet this range of requirements, this project will investigate double hybrid materials (DHM), which correspond to the "brick and mortar" model often found in nature, as they consist of granules of a hybrid material and an organic matrix (collagen). The hybrid granules, in this case, are composed of an organic (collagen) and an inorganic (silica) component. This material system allows – by pre-treatment of the collagen in different stages of synthesis and by a choice of component ratios – to specifically modify the degradability of the DHM. The DHM can thus be adapted to bone regeneration and, if necessary, stimulate it. To this end, the collagen of the DHM (more precisely of their components) will be pre-damaged by radiolytic degradation using gamma irradiation to stimulate osteoclastic material resorption. The flexibility of the material system allows collagen to be used at all different levels of the hierarchy. Furthermore, the variable material synthesis allows the use of both radiation-treated and untreated collagen at all levels. Thus, the material can address osteoclast stimulation, i.e. accelerated resorbability, and rapid acellular degradation with simultaneous high mechanical strengths. In order to be able to guarantee this processes even in case of large bone defects and correspondingly large biomaterial specimens, a further hierarchical level will be added by means of extrusion-based 3D plotting. The DHM are processed by paste extrusion to macroporous scaffolds, whereby a void phase enables the accessibility of the strand surfaces for bone cells. Here, gamma irradiation serves to improve the viscoelastic properties of the matrix collagen to realize good processing via 3D plotting.In future, degradation and resorption of bone substitute materials might be adjustable according to the bone status and general patient condition via pre-treatment of the collagen-containing composites.