Develop manganese-containing porous scaffolds with vasculature-like channels for potential applications in craniofacial bone regeneration

项目摘要 人工合成多孔支架作为自体骨和异体骨的替代材料，在修复过程中存在一定的局限性 由于血管化和骨形成不足导致的临界尺寸颅面骨缺损。到 为了解决这些问题，在这个项目中，我们建议构建一个新的血管样通道， 在多孔β-磷酸三钙中构筑并添加二氧化锰（MnO 2）空心纳米粒子 （b-TCP）支架以促进新血管生长并刺激骨生成。这一战略 利用新的模拟血管样通道来刺激细胞募集， 新血管的侵入，并利用新的无机含锰纳米粒子，以促进 成骨具体而言，将采用结合3D打印的模板铸造技术， 开发血管状通道的多孔MnO 2/b-TCP支架。MnO 2浓度 b-TCP中的纳米颗粒，血管样通道的最佳通道尺寸，以及体内细胞 将充分研究新支架的浸润、组织生物相容性和血管化。到 为达致这个目标，我们会致力达致以下三个具体目标。目的1：研究MnO 2的作用 纳米颗粒对多孔b-TCP支架的机械、物理化学和生物学特性的影响。 目的2：研究3D通道对机械、物理化学和生物学的影响 多孔MnO 2/b-TCP支架的性能。目的3：检查组织生物相容性，促血管生成， 在小鼠皮下模型中，通道支架的细胞指导功能。在我们完成 这个为期三年的项目，我们将产生一个新的支架与模仿结构， 促进颅面骨组织再生的成骨刺激成分。本拟议项目 将是我们长期目标的基础，将这种合成多孔支架用于再生， 巨大的颅面骨缺损

Project Summary As bone substitutes for autografts and allografts, synthetic porous scaffolds have limitations in the repair of critical-sized craniofacial bone defects due to insufficient vascularization and bone formation. To address these issues, in this project we propose to construct a new vasculature-like channels internal structure and add manganese dioxide (MnO2) hollow nanoparticles in a porous beta-tricalcium phosphate (b-TCP) scaffold to facilitate new blood vessel growth and stimulate osteogenesis. This strategy harnesses the new mimicking vasculature-like channels to stimulate cell recruitment and promote the invasion of new blood vessels, and utilizes the new inorganic Mn-containing nanoparticles to promote osteogenesis. Specifically, a template-casting technique combining 3D printing will be employed to develop vasculature-like channeled porous MnO2/b-TCP scaffolds. The concentrations of MnO2 nanoparticles in the b-TCP, the optimal channel size of the vasculature-like channels, and the in vivo cell infiltration, tissue biocompatibility, and vascularization of the new scaffold will be fully investigated. To achieve this goal, we will pursue the following three specific aims. Aim 1: Investigate the effect of MnO2 nanoparticles on the mechanical, physicochemical, and biological properties of porous b-TCP scaffolds. Aim 2: Investigate the effect of 3D channels on the mechanical, physicochemical, and biological properties of porous MnO2/b-TCP scaffolds. Aim 3: Examine the tissue biocompatibility, pro-angiogenic, cell-instructive functions of the channeled scaffold in a mouse subcutaneous model. After we complete this three-years proposed project, we will generate a new scaffold with mimicking structures and osteogenesis-stimulating components for craniofacial bone tissue regeneration. This proposed project will be the foundation for our long-term goal to translate this synthetic porous scaffold for the regeneration of large craniofacial bone defects.