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.

无机聚合物在骨组织再生工程中的生物矿化潜力 项目摘要 骨移植是第二常见的组织移植手术，有 220 万例手术在进行 在全球范围内进行。治疗大面积不愈合颅面缺损的临床金标准是收获 并移植自体移植物。然而，自体移植物的供应有限，术后 发病频繁。由于对钛基、聚合物基和陶瓷基骨科材料的依赖 植入物、标准合成骨支架通常会导致感染或骨退化等并发症 由于植入物与周围自然环境之间的几何形状和物理特性不匹配 骨骼结构。因此，对于用于组织再生的新型多尺度材料存在知识空白 工程旨在减轻骨质流失，并促进宿主骨结构周围的骨增殖。长- 本学期的研究目标是通过整合复合材料科学来发现新型多尺度骨支架， 物理科学和转化医学。我的长期职业目标是实现骨骼组织制造 通过先进材料科学、物理科学和转化技术的整合实现再生 药品。我计划重点研究一类新型材料，即在低温下合成的无机聚合物 通过将硅铝酸盐源溶解在碱金属硅酸盐溶液中来调节温度。我的研究假设是 无机聚合物材料可用于模拟多尺度微观结构和机械行为 由于其纳米级结构、介孔性和优异的性能，致密骨并诱导骨再生 机械性能。纳米级结构特征通常与骨整合性的改善有关 而微孔则促进细胞迁移、血管化和神经支配。我的初步结果有 研究表明，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具有刚度和强度值 接近致密骨，这表明可以通过以下方式获得更接近的机械性能匹配 材料设计。我的工作表明，无机聚合物与小鼠成纤维细胞具有生物相容性，并且 人类间充质细胞。然而，目前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 这一发现为转化再生生物工程阐明因素奠定了基础 推动新型工程无机聚合物支架的生物相容性。两个具体研究目标 被提议。 Aim One 将为生物相容性无机聚合物骨提供优化的合成路线 对无机中细胞附着和迁移机制有基本了解的支架 聚合物支架。目标二将使人们对成骨细胞分化和成骨细胞分化有基本的了解 无机聚合物纳米复合材料的矿化机制。目标三将调查潜力 无机聚合物支架加速大鼠体内复杂颅面缺损的愈合 模型。拟议的 RO3 项目将为骨组织再生工程生产新型材料。