Evaluation of angiogenesis and bone regeneration after reconstruction of the facial skeleton using bioactive scaffolds

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The aim of this project proposal is to investigate the influence of a novel polymer based therapy (enabled by RAFT polymerization) aimed at transfection and expression of the growth factor BMP-2. In addition to the beneficial effect on osteogenesis achieved in this way, a biodegradable scaffold (CSIRO) will be investigated in vivo in regard to its osteogenic properties. Furthermore, the role of pore size (250 and 500 microns) of the scaffold material will be evaluated in terms of angiogenesis within the regenerated bone tissue. For this purpose a previously established critical-size-defect animal model is used, where scaffolds are placed in the angle of the jaw of the rat. The angiogenesis of new bone and the interconnectivity (with respect to the neovascularization) between the scaffold and the surrounding physiological bone are factors which have not been adequately studied so far. The possibility to investigate bone and vascular architecture simultaneously (microCT) can potentially revolutionize the understanding of bone healing. Traditional histomorphometric approaches had to manage with 2-dimensional parameters. So far, there is no study that could 3-dimensional simultaneously examine bone and blood vessels in the jaw of the rat. Here, it is envisaged to collect the same scans using a high resolution clinical CT, which can be used for patient diagnosis, and to correlate the results of the bony prameters. The aim is to examine whether nondestructive measurements are possible, which would allow a considerable saving of experimental animals for subsequent experiments. For compromised patients with medical conditions or those on medications that prohibit longer OPs, or prevent non autologous transplants, there is currently no alloplastic material which is able to successfully replace the bone functionally stable in the maxillofacial area. In such cases, the scaffold with its optimized characteristics in conjunction with the non-toxic transfection-based polymer therapy could provide a solution, leading to functionally stable bone in the maxillofacial region for the first time by an alloplastic material. This will subsequently be investigated in a large animal model to establish proof of concept. Following this, the manufacturing process, which offers technical simplicity at low cost, is expected to contribute to a quick translation. Importantly, no complicated, time-consuming and expensive methods such as CAD/CAM/3D-printing are necessary. Overall, significant commercial interest after a successful animal experiment has a high likelyhood.