Biofabrication of New Composite Scaffolds for Bone Tissue Engineering Applications

最近的评论强调了电纺纳米纤维在各种组织工程应用中的主要潜力。该研究计划旨在利用静电纺丝技术和水凝胶制备新型可生物降解的骨组织工程复合支架。物理特性（组成、结构、孔径等）的熔融电纺聚（ε-己内酯）（PCL）网将首先优化，以促进骨祖细胞的附着和分化。然后将使用纤维蛋白-藻酸盐水凝胶以受控方式递送的内皮细胞和生长因子掺入PCL网片（先前接种有骨祖细胞）中以促进血管形成。事实上，骨修复的一个主要挑战是提供一个不仅促进骨矿化，而且促进血管化的环境。研究将细分如下：** 目标1：通过熔融静电纺丝、表面改性和骨祖细胞制备具有特定物理特性的矿化聚（ε-己内酯）（PCL）补片。将具有不同孔径的PCL网进行熔融电纺，用磷酸钙（CaP）涂覆，并通过扫描电子显微镜和能量色散X射线光谱进行表征。然后在补片表面培养骨祖细胞进行矿化。*目标二：在灌注条件下，测定矿化PCL补片（在目标1中开发）与负载血管内皮生长因子（VEGF）-165和内皮细胞的纤维蛋白-藻酸盐水凝胶组合的生物学和机械性能。将进行SEM、碱性磷酸酶定量、共聚焦显微镜、免疫细胞化学、组织学/免疫组织化学和机械试验，以评价结构的生物学和机械性能。**这项拟议中的研究使用尖端技术来制造新的矿化和血管化骨替代品。自体骨移植通常用于愈合临界尺寸的骨缺损，但骨替代品的使用提供了这种侵入性技术的替代方案。然而，目前的骨替代物仍然面临着显著的局限性，包括供应不足、成本高以及替代物不能与周围宿主组织整合。因此，拟议的研究将为加拿大的保健系统带来切实的好处。此外，它还可能导致新的可申请专利的产品和/或工艺最终可用于商业化。最后，这项研究只有通过招募高素质的团队成员才有可能，他们将接触到最先进的技术，并将有独特的机会在基础研究和应用研究之间的界面上获得多学科培训。

Recent reviews have highlighted the major potential of electrospun nanofibers for various tissue engineering applications. The proposed research program aims to fabricate new biodegradable composite scaffolds for bone tissue engineering applications using electrospinning technologies and hydrogels. The physical characteristics (composition, architecture, pore size, etc.) of melt electrospun poly(e-caprolactone) (PCL) meshes will first be optimized to promote osteoprogenitor cell attachment and differentiation. Endothelial cells and growth factors, delivered in a controlled manner using fibrin-alginate hydrogels, will then be incorporated into the PCL meshes (previously seeded with osteoprogenitor cells) to promote vascularization. Indeed, a major challenge for bone repair is to provide an environment that promotes not only bone mineralization, but also vascularization. Research will be segmented as follows: ******Objective 1: Fabricate mineralized poly(e-caprolactone) (PCL) meshes with specific physical characteristics by using melt electrospinning, surface modification, and osteoprogenitor cells. PCL meshes with different pore sizes will be melt electrospun, coated with calcium phosphate (CaP) and characterized by scanning electron microscopy and energy dispersive X-ray spectroscopy. Osteoprogenitor cells will then be cultured on the mesh surface for mineralization.***Objective 2: Determine the biological and mechanical properties of the mineralized PCL meshes (developed in Objective 1) combined with fibrin-alginate hydrogels loaded with vascular endothelial growth factor (VEGF)-165 and endothelial cells, under perfused conditions. SEM, quantification of alkaline phosphatase, confocal microscopy, immunocytochemistry, histology/immunohistochemistry, and mechanical testing will be performed to evaluate the biological and mechanical properties of the constructs.******The proposed research uses cutting-edge technology to fabricate new mineralized and vascularized bone substitutes. Autologous bone grafts are often used to heal critical-size bone defects, but the use of bone substitutes presents an alternative to this invasive technique. However, current bone substitutes are still facing significant limitations including insufficient supply, high cost and the inability of the substitutes to integrate with the surrounding host tissue. The proposed research will therefore provide tangible benefits to the Canadian health-care system. In addition, it will potentially lead to new and patentable products and/or processes eventually transferable for commercialization. Finally, this research will only be possible by recruiting highly qualified team members, who will be exposed to state-of-the-art technologies and will have a unique opportunity to acquire multidisciplinary training at the interface between fundamental and applied research.