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

本项目提案的目的是研究一种新的基于聚合物的治疗方法（由RAFT聚合实现）对生长因子BMP-2的转染和表达的影响。除了以这种方式实现的成骨的有益作用外，生物可降解支架（CSIRO）将在体内研究其成骨特性。此外，支架材料孔径（250微米和500微米）的作用将在再生骨组织内的血管生成方面进行评估。为此，使用了先前建立的临界尺寸缺陷动物模型，其中支架放置在大鼠颚的角度。新骨的血管生成以及支架与周围生理骨之间的相互连接（关于新生血管的形成）是迄今尚未充分研究的因素。同时研究骨和血管结构（微ct）的可能性可能会彻底改变对骨愈合的理解。传统的组织形态测量方法必须处理二维参数。到目前为止，还没有一项研究可以同时对大鼠颌骨的骨骼和血管进行三维检查。在这里，设想使用高分辨率临床CT收集相同的扫描结果，可用于患者诊断，并将骨骼参数的结果关联起来。目的是检查是否有可能进行无损测量，这将为后续实验节省大量实验动物。对于那些身体状况不佳的患者，或者那些正在接受药物治疗的患者，或者那些阻止非自体移植的患者，目前还没有同种异体材料能够成功地替代颌面区域功能稳定的骨。在这种情况下，具有优化特性的支架与无毒转染聚合物疗法相结合，可以提供一种解决方案，首次通过同种异体材料在颌面区域实现功能稳定的骨骼。随后将在大型动物模型中进行研究，以建立概念证明。在此之后，以低成本提供技术简单性的制造过程有望有助于快速翻译。重要的是，不需要复杂，耗时和昂贵的方法，如CAD/CAM/ 3d打印。总的来说，成功的动物实验后很有可能产生重大的商业利益。

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.