NSF/FDA Scholar in Residence Program on Physico-Chemical Characterization and In Vitro Biological Evaluation of 3D Printed Ceramics

非技术总结：这个驻学学者项目将寻求更好地理解两种新型3D打印骨替代物，它们基于惰性生物陶瓷材料氧化锆和可生物降解生物陶瓷材料磷酸钙。磷酸钙是用于骨置换植入物（例如，合成骨移植物）的引人注目的材料，因为它刺激医疗设备表面的骨形成。一种新型的磷酸钙材料将被3D打印，它包含一种梯度，一种磷酸钙可以快速释放骨骼刺激化学物质，另一种磷酸钙可以作为植入物和周围骨骼之间的持久界面。由于具有微纳米粗糙特征的氧化锆表面比光滑的氧化锆表面具有更好的骨整合性能，因此将通过3D打印和激光纹理技术创建一种新型的图案氧化锆生物材料。北卡罗来纳州立大学和FDA研究人员之间的合作将寻求了解新型3D打印陶瓷的生物陶瓷加工参数、物理特性、化学特性、机械特性和体外生物反应之间的关系。该项目的成果将减少与3D打印陶瓷相关的知识空白，并将导致新型合成骨移植物，这将为患有各种骨科疾病的患者提供改善的生活质量。“科学星期六”的讲座和实践活动将向北卡罗莱纳自然科学博物馆的小学生、初中生、高中生和其他参观者传播研究成果。有关医疗3D打印最新进展的信息，包括该项目的成果，将通过在线研讨会系列传播给北卡罗莱纳州的教师。技术总结：该项目将利用北卡罗来纳州立大学在新型生物材料的加工和表征方面的独特能力，以及FDA在新型生物材料的生物表征方面的独特能力，系统地评估制造、后处理（例如，图图化和灭菌），以及对两种新型3D打印生物陶瓷（图案氧化锆和功能梯度磷酸钙）的生物反应。该项目的第一阶段将涉及了解3D打印图案氧化锆和功能梯度磷酸钙部件的物理化学特性。例如，扫描电子显微镜和原子力显微镜将用于评估3D打印生物陶瓷表面特征的再现性和均匀性。x射线衍射和x射线光电子能谱将分别用于检查3D打印生物陶瓷的微观结构和杂质的存在。该项目的第二阶段将涉及使用纳米压痕和四点弯曲测试来了解3D打印生物陶瓷的机械性能。该项目的第三阶段将利用FDA的设施，通过蛋白质吸收、细胞粘附动力学、细胞形态、细胞增殖和成骨分化研究，评估应用相关细胞（例如骨髓基质细胞和成骨细胞样细胞）与3D打印生物陶瓷之间的相互作用。该提案的独特之处在于，PI团队将系统地评估两种新型3D打印生物陶瓷的制造、后处理、材料特性、机械性能和生物响应。该驻校学者项目获得的数据将与3D打印生物陶瓷医疗器械的发展以及促进3D打印医疗器械监管决策的国际共识标准的完善有关。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Non-Technical Summary: This Scholar-in-Residence project will seek to better understand two new types of 3D printed bone replacements that are based on an inert bioceramic material, zirconia, and a biodegradable bioceramic material, calcium phosphate. Calcium phosphate is a compelling material for bone replacement implants (e.g., synthetic bone grafts) since it stimulates bone formation on the surface of medical device. A new type of calcium phosphate material will be 3D printed, which contains a gradient between (a) a form of calcium phosphate that rapidly releases bone-stimulating chemicals and (b) a form of calcium phosphate that can serve as long-lasting interface between an implant and the surrounding bone. Since zirconia surfaces with micro- and nano-roughened features exhibit better bone integration properties than smooth zirconia surfaces, a new type of patterned zirconia biomaterial will be created by 3D printing and laser texturing. A collaboration between NC State University and FDA researchers will seek to understand the relationships among the bioceramic processing parameters, physical properties, chemical properties, mechanical properties, and in vitro biological responses for the novel 3D printed ceramics. The results of this project will reduce knowledge gaps related to 3D printed ceramics and will lead to new types of synthetic bone grafts, which will provide an improved quality of life for patients who suffer from various orthopedic conditions. Science Saturday lectures and hands-on activities will disseminate results from the project to elementary school students, middle school students, high school students, and other visitors to the North Carolina Museum of Natural Sciences. Information on recent advances in medical 3D printing, including results from this project, will be disseminated to teachers across the state of North Carolina via an online workshop series.Technical Summary: The project will take advantage of the unique capabilities at NC State University related to processing and characterization of novel biomaterials and at the FDA related to biological characterization of novel biomaterials to systematically evaluate fabrication, post processing (e.g., patterning and sterilization), and the biological response to two new types of 3D printed bioceramics, patterned zirconia and functionally gradient calcium phosphate. Phase I of the project will involve understanding the physico-chemical properties of the 3D printed patterned zirconia and functionally gradient calcium phosphate parts. For example, scanning electron microscopy and atomic force microscopy will be used to assess the reproducibility and uniformity of the surface features of the 3D printed bioceramics. X-ray diffraction and X-ray photoelectron spectroscopy will be used to examine the microstructure and the presence of impurities in the 3D printed bioceramics, respectively. Phase II of the project will involve the use of nanoindentation and four-point bend testing to understand the mechanical properties of the 3D printed bioceramics. Phase III of the project will utilize FDA facilities to evaluate interactions between application-relevant cells (e.g., bone marrow stromal cells and osteoblast-like cells) and the 3D printed bioceramics through protein absorption, cell adhesion dynamics, cell morphology, cell proliferation, and osteogenic differentiation studies. This proposal is unique in that the PI team will systematically evaluate fabrication, post processing, material characteristics, mechanical properties, and biological response to two new types of 3D printed bioceramics. The data obtained in this Scholar-in-Residence project will be relevant to the development of 3D printed bioceramic medical devices and the improvement of international consensus standards that facilitate regulatory decision-making for 3D printed medical devices.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.