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

• Applicant: Dr.-Ing. Benjamin Kruppke
• Subject Area: Biomaterials
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497439310

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.

• DFG Programme: Research Grants