Biomineralization potential of inorganic polymer for bone tissue regenerative engineering

无机聚合物在骨组织再生工程中的生物矿化潜力

• 批准号: 10728774
• 负责人: Ange-Therese Akono
• 金额: $ 14.15万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-06 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728774
• 关键词: Acceleration; AlamarBlue; Alkali Metals; Alkalies; Alkaline Phosphatase; Animal Model; Automobile Driving; Award; Biological Assay; Biomedical Engineering; Biomimetics; Bone Growth; Bone Regeneration; Bone Tissue; Bone Transplantation; Bone structure; Cations; Cell Proliferation; Cell Wall; Cell-Matrix Junction; Cells; Ceramics; Chemicals; Chemistry; Clinical; Craniofacial Abnormalities; Defect; Engineering; Exhibits; Fibroblasts; Future; Generations; Geometry; Goals; Grant; Growth Factor; Harvest; Histologic; Human; Hydration status; Implant; In Vitro; Infection; Inorganic Chemistry; Knowledge; Link; Mathematics; Mesenchymal; Mesenchymal Stem Cells; Methods; Modeling; Morbidity - disease rate; Mus; National Center for Advancing Translational Sciences; Orthopedics; Osteoblasts; Osteogenesis; Outcome; Performance; Polymers; Porosity; Potassium; Procedures; Proliferating; Property; Public Health; Qualifying; Rattus; Regenerative engineering; Research; Roentgen Rays; Route; Scanning Electron Microscopy; Silicates; Sodium; Source; Structure; Testing; Tissue Transplantation; Tissues; Titanium; Training; Transplantation; Vascularization; Work; aluminosilicate; biomaterial compatibility; biomineralization; bone; bone loss; bone scaffold; career; cell motility; cold temperature; comparative; cortical bone; craniofacial complex; design; fabrication; healing; high reward; high risk; improved; in vivo; in vivo evaluation; innovation; learning materials; materials science; mechanical behavior; mechanical properties; micropore; mineralization; nanocomposite; nanomaterials; nanopolymer; nanoscale; nerve supply; novel; osteoblast differentiation; physical property; physical science; regenerative; regenerative tissue; scaffold; translational medicine; tricalcium phosphate

Biomineralization potential of inorganic polymer for bone tissue regenerative engineering Project Abstract Bone grafting is the second most common tissue transplantation procedure, with 2.2 million procedures being conducted worldwide. The clinical gold standard for treating large non-healing craniofacial defects is to harvest and transplant autogenous grafts. However, the supply of autogenous grafts is limited, and post-surgery morbidities are frequent. Due to a reliance on titanium-based, polymer-based, and ceramic-based orthopaedic implants, standard synthetic bone scaffolds often result in complications such as infection or bone degeneration due to a mismatch in both geometry and physical properties between the implant and the surrounding natural bone structure. Therefore, there is a gap of knowledge in novel multiscale materials for tissue regenerative engineering to mitigate bone loss, and promote bone proliferation around the host bone structure. The long- term research goal is to discover novel multiscale bone scaffolds by integrating composite materials science, physical sciences, and translational medicine. My long-term career goal is to enable tissue fabrication for bone regeneration through the integration of advanced materials science, physical sciences, and translational medicine. I plan to focus on a new class of materials, inorganic polymers that are synthesized at low temperatures by dissolving an aluminosilicate source in an alkali-silicate solution. My research hypothesis is inorganic polymer materials can be used to mimic the multiscale microstructure and mechanical behavior of compact bone and induce bone regeneration thanks to their nanoscale structure, mesoporosity, and excellent mechanical properties. Nanoscale structural features are frequently linked to improved osseointegrativity whereas as micropores promote cell migration, vascularization and innervation. My preliminary results have shown that the pore size and total porosity of inorganic polymer composites can be modified by adjusting the mix design and the processing route. Unreinforced pure inorganic polymer exhibits stiffness and strength values close to that of compact bone, suggesting that a closer match in mechanical properties can be obtained through materials design. My work has shown that inorganic polymer, is biocompatible with mouse fibroblast cells and human mesenchymal cells. However, what is yet unknown are the cell-wall interactions, the osteoblast mineralization mechanisms, and the in-vivo performance for inorganic polymer scaffolds. Therefore, this discovery has laid the groundwork to move to translational regenerative bioengineering to elucidate the factors driving the biocompatibility of novel engineered inorganic polymer-based scaffold. Two specific research aims are proposed. Aim One will yield optimized synthesis routes for biocompatible inorganic polymer-based bone scaffolds with a fundamental understanding of the mechanisms of cell attachment and migration in inorganic polymer scaffolds. Aim Two will enable a fundamental understanding of osteoblast differentiation and mineralization mechanisms in inorganic polymer nanocomposites. Aim Three will investigate the potential of inorganic polymer scaffolds to accelerate the healing of complex craniofacial defects in-vivo using rat animal models. The proposed RO3 project will yield novel materials for bone tissue regenerative engineering.

骨组织再生工程用无机高分子材料的生物矿化潜力 项目摘要 骨移植是第二种最常见的组织移植手术， 在全球范围内进行。治疗大型非愈合性颅面缺损的临床金标准是采集 移植自体移植物然而，自体移植物的供应是有限的，并且手术后 发病率很高。由于对钛基、聚合物基和陶瓷基骨科的依赖， 标准的合成骨支架通常会导致并发症，如感染或骨退化 由于植入物和周围自然环境之间的几何形状和物理性质不匹配 骨骼结构因此，在用于组织再生的新型多尺度材料方面存在知识空白 工程化以减轻骨丢失，并促进宿主骨结构周围的骨增殖。很长的- 长期的研究目标是通过整合复合材料科学， 物理科学和转化医学。我的长期职业目标是使骨组织制造成为可能 再生通过先进的材料科学，物理科学和转化的整合， 药我计划把重点放在一类新的材料上，即在低温度下合成的无机聚合物。 通过将铝硅酸盐源溶解在碱金属硅酸盐溶液中来在温度下进行。我的研究假设是 无机聚合物材料可用于模拟多尺度微结构和机械行为， 由于其纳米级结构、中孔性和优异的生物相容性， 力学性能纳米级结构特征通常与骨整合性的改善有关 而As微孔促进细胞迁移、血管化和神经支配。我的初步结果显示 表明无机聚合物复合材料的孔径和总孔隙率可以通过调节 配合比设计和加工路线。未增强的纯无机聚合物表现出刚度和强度值 接近密质骨，这表明可以通过以下方式获得更接近的力学性能匹配： 材料设计我的工作表明，无机聚合物，与小鼠成纤维细胞是生物相容的， 人类间充质细胞然而，目前尚不清楚的是细胞壁的相互作用，成骨细胞 矿化机制和无机聚合物支架的体内性能。因此本 这一发现为转向转化再生生物工程来阐明这些因素奠定了基础 驱动新型工程无机聚合物基支架的生物相容性。两个具体的研究目标 被提议。目的优化无机聚合物基生物相容性骨的合成路线 支架与细胞附着和迁移机制的基本理解，在无机 聚合物支架。目的二将使成骨细胞分化的基本理解， 无机聚合物纳米复合材料的矿化机制。目标三将研究 无机聚合物支架促进大鼠复杂颅面缺损的体内愈合 模型拟议的RO 3项目将产生用于骨组织再生工程的新型材料。