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

开发具有类血管通道的含锰多孔支架，在颅面骨再生中具有潜在应用

• 批准号: 10514798
• 负责人: Yunqing Kang
• 金额: $ 44.4万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10514798
• 关键词: 3-Dimensional; 3D Print; Address; Affect; Allografting; Anatomy; Architecture; Autologous Transplantation; Biocompatible Materials; Biological; Biological Testing; Biomedical Research; Blood Vessels; Bone Regeneration; Bone Substitutes; Bone Tissue; Cells; Ceramics; Chemicals; Complex; Congenital Disorders; Data; Defect; Florida; Foundations; Goals; Growth; Growth Factor; Hispanic-serving Institution; Implant; In Vitro; Infiltration; Instruction; Ions; Malignant Neoplasms; Manganese; Mechanics; Mediating; Modeling; Mus; Natural regeneration; Osteogenesis; Property; Publications; Shapes; Structure; Survival Rate; Techniques; Testing; Tissue Engineering; Tissues; Translating; Transplantation; Trauma; Universities; Vascularization; Work; angiogenesis; biomaterial compatibility; bioscaffold; calcium phosphate; cell motility; craniofacial bone; craniofacial repair; design; experimental study; graduate student; implantation; in vivo; nanomaterials; nanoparticle; recruit; regenerative; regenerative approach; repaired; scaffold; side effect; stem cell differentiation; stem cell therapy; stem cells; subcutaneous; success; tissue regeneration; tissue repair; tissue stem cells; tricalcium phosphate; undergraduate student

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.

项目概要 作为自体移植物和同种异体移植物的骨替代物，合成多孔支架在修复方面存在局限性 由于血管化和骨形成不足而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，我们建议在内部构建一个新的类似脉管系统的通道 结构并在多孔β-磷酸三钙中添加二氧化锰（MnO2）中空纳米粒子 (b-TCP) 支架促进新血管生长并刺激成骨。这个策略 利用新的模仿脉管系统的通道来刺激细胞募集并促进 侵袭新血管，并利用新型无机含锰纳米颗粒促进 成骨。具体来说，将采用结合3D打印的模板铸造技术 开发类似脉管系统的通道式多孔 MnO2/b-TCP 支架。 MnO2 的浓度 b-TCP中的纳米颗粒、类脉管系统通道的最佳通道尺寸以及体内细胞 新支架的渗透、组织生物相容性和血管化将得到全面研究。到 为实现这一目标，我们将追求以下三个具体目标。目标 1：研究 MnO2 的影响 纳米颗粒对多孔 b-TCP 支架机械、物理化学和生物特性的影响。 目标 2：研究 3D 通道对机械、物理化学和生物的影响 多孔MnO2/b-TCP支架的特性。目标 3：检查组织生物相容性、促血管生成、 小鼠皮下模型中通道支架的细胞指导功能。当我们完成后 在这个为期三年的拟议项目中，我们将生成一个具有模仿结构的新脚手架 用于颅面骨组织再生的成骨刺激成分。本拟议项目 将成为我们将这种合成多孔支架转化为再生的长期目标的基础 大面积颅面骨缺损。