Entwicklung poröser, multifunktionaler Materialien zur Knochenregeneration

Abstract

Bone defects can occur, among other things, as a result of mechanical trauma, bacterial infections or even curettage after a tumour. Some of the defects can no longer be healed independently by the body. This can be accompanied by great impairment in everyday life, so that the long healing process requires optimal support. The bone itself is a composite material, which gives it its unique properties. The inorganic component is hydroxyapatite. Its crystals are embedded in the organic collagen. The outer layer of the bone is the dense compacta, which envelops the open-pored cancellous bone; both parts are highly vascularised. Bone tissue is subject to a perpetual process of building up and breaking down so that a healthy balance is normally produced. This allows the body to increase bone density in response to permanent increased stress. This occurs in different signalling cascades to the bone cells, so that, for example, osteoblasts build up bone or osteoclasts break it down. The differentiation of mesenchymal stem cells into bone cells is also part of the complex balance, which maintains the health of the bone tissue. Proteins, growth factors, hormones and ions are factors which influence this balance. In the context of this work, an elastic, open-pored bone regeneration material is the goal. The implant should be biocompatible and -active, osteogenic and -conductive and degradable. Especially the influence of ions shall be used to achieve the mentioned requirements. For this purpose, a composite material of a silica-calcium based bioactive glass and the synthetic biopolymer polyglycerol sebacate and its derivative with calcium glycerol sebacate will be synthesised using both microwave radiation and conventional heating. The bioactive glass is equipped with nanopores that can be loaded with strontium chloride. In total, the implant releases orthosilicic acid, calcium, phosphate and strontium ions, each of which plays a crucial role in the signalling cascades of bone tissue homeostasis. The bioactive glass was successfully produced via the sponge-template process, whose mass of silica material can be predicted and has open macropores. The replica obtained was equipped with mesopores and loaded with strontium chloride, although the incorporation of other molecules or salts are also possible. Polyglycerol sebacate could be successfully synthesised as a copolymer with calcium glycerol sebacate, which could be confirmed by nuclear magnetic resonance spectroscopy. Microwave synthesis in the sense of green chemistry could be established as an alternative synthesis route. The combined materials resulted in an elastic, open-pored scaffold, which is degradable. The boundary conditions of the coating process were explored. In release experiments, it was shown that orthosilicic acid, calcium and phosphate ions can be released over 65 days and strontium ions over 14 days in concentrations that are close to the physiologically effective concentrations, so that an osteogenic and -conductive effect can be expected. The biocompatibility of the scaffold was demonstrated in cell tests. The surface of the implant offers the possibility of adhesion on the inside as well as on the outside, whereby a conventionally produced scaffold type based on calcium glycerol sebacate performed best. Studies in the animal model compared scaffolds with and without incorporated calcium glycerol phosphate. Both showed very good compatibility, hardly any immune reactions and a high tendency to vascularisation. The scaffold with calcium glycerol phosphate showed significantly higher vascularisation which is an important cornerstone for successful healing of a bone defect.