Endobone

• Project number: LSC16_024
• Project Management: Stefan Nehrer, Danube University Krems / Department of Regenerative Medicine
• Project partners: Karl Landsteiner University for Health Sciences / Division of Biomechanics
• Project duration: 48 months from 1 January 2018

Background

Techniques for inserting a new piece of bone to treat large bone defects often involve the implantation of an allogenic bone graft to replace the damaged tissue. However, there is often poor integration of the graft and no functioning anastomosis, which is needed for blood vessels of the existing tissue to migrate into the graft. Therefore, many unresolved issues need to be investigated to improve clinical outcomes involving fractures, osteonecrosis and osteoporosis. Versatile tissue engineering strategies have already been developed to promote bone regeneration. The most common method involves stimulating bone development to regenerate bone, but this strategy is still ineffective. From the very beginning of research in bone tissue engineering, the idea was to mimic natural processes of bone formation by developing mechanisms for the formation of long bones (= endochondral ossification). In this project, we aim to develop bone regeneration strategies involving natural biomaterials with incorporated extracellular matrix of cartilage (= cartilage derived extracellular matrix; CD-ECM). We hypothesise that a cartilage-like template on a solid biomaterial forms a new tissue that resembles native bone in structure and functionality. To test this hypothesis, we will compare new bone formation using our proposed model with bone grafts used in the clinic. Hypertrophic chondrocytes, i.e. chondrocytes on the way to bone formation, will be embedded in the biomaterials provided with CD-ECM and the formation of a mineralised matrix will be investigated by biochemical analysis and histological methods. Furthermore, micro-computed tomography (μCT), a method in which the construct is not destroyed, is used to generate multi-slice three-dimensional images to visualise calcification and bone formation. This allows computer modulation and simulation, enabling finite element analysis to describe the stiffness and resistance of these formed constructs. The CD-ECM engineered biomaterials will then be implanted subcutaneously in rats with or without hypertrophic chondrocytes to study the de novo mineralisation of the matrix. Furthermore, bone formation will be studied by μCT as well as biochemical, biomechanical and computational methods. This interdisciplinary approach would help bioresponsive materials to recapitulate the natural mechanism of native bone healing.