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.

无机聚合物对骨组织再生工程的生物矿化潜力 项目摘要 骨移植是第二大最常见的组织移植程序，其中220万程序为 在全球进行。治疗大型非治疗颅面缺陷的临床金标准是收获 和移植自体移植。但是，自动移植物的供应受到限制，手术后的供应 病毒频繁。由于依赖基于钛，基于聚合物和基于陶瓷的骨科 植入物，标准合成骨支架通常会导致并发症，例如感染或骨变性 由于植入物和周围自然之间的几何形状和物理特性不匹配 骨结构。因此，在新型多尺度材料的新知识上有一定差距 工程以减轻骨质流失，并促进宿主骨结构周围的骨增殖。长期 术语研究目标是通过整合复合材料科学来发现新型的多尺寸骨支架， 物理科学和转化医学。我的长期职业目标是使骨骼的组织制造 通过整合高级材料科学，物理科学和翻译的再生 药品。我计划专注于新的材料，无机聚合物，这些聚合物在低处合成 通过将铝硅酸盐源溶解在碱 - 硅酸盐溶液中的温度。我的研究假设是 无机聚合物材料可用于模仿多尺度的微观结构和机械行为 紧凑的骨骼并诱导骨骼再生，这要归功于其纳米级结构，介孔性和出色的 机械性能。纳米级结构特征经常与改善的骨整合性有关 而作为微孔促进细胞迁移，血管化和神经的迁移。我的初步结果 表明可以通过调整无机聚合物复合材料的孔径和总孔隙率。 混合设计和处理路线。未增强的纯无机聚合物表现出刚度和强度值 接近紧凑的骨头，表明可以通过 材料设计。我的工作表明，无机聚合物，与小鼠成纤维细胞和 人间充质细胞。但是，尚不清楚的是细胞壁相互作用，成骨细胞 矿化机制以及无机聚合物支架的体内性能。因此，这个 发现为转化再生生物工程奠定了基础，以阐明这些因素 推动新型工程无机聚合物脚手架的生物相容性。两个具体的研究目的 提出了。 AIM ONE将产生针对生物相容性无机聚合物骨的优化合成途径 脚手架对无机细胞附着和迁移的机制有基本的理解 聚合物支架。目标两个将使对成骨细胞区分的基本了解和 无机聚合物纳米复合材料中的矿化机制。 AIM三将调查潜力 无机聚合物支架可加速使用大鼠动物体内复杂颅面缺损的愈合 型号。拟议的RO3项目将产生用于骨组织再生工程的新型材料。