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

非技术总结：这个常驻学者项目将寻求更好地了解两种新型的3D打印骨替代物，这两种材料基于惰性生物陶瓷材料氧化锌和可生物降解的生物陶瓷材料磷酸钙。磷酸钙是骨替代植入物(如人工骨移植)的理想材料，因为它能刺激医疗器械表面的骨形成。一种新型的磷酸钙材料将被3D打印出来，它包含一个梯度，介于(A)一种快速释放骨刺激化学物质的磷酸钙和(B)一种可以作为植入物和周围骨骼之间持久界面的磷酸钙。由于具有微米和纳米粗糙特征的氧化锆表面表现出比光滑的氧化锆表面更好的骨整合性能，因此将通过3D打印和激光毛化来创造一种新型的图案化氧化锆生物材料。北卡罗来纳州立大学和FDA研究人员的合作将寻求了解新型3D打印陶瓷的生物陶瓷工艺参数、物理性能、化学性能、机械性能和体外生物响应之间的关系。该项目的成果将减少与3D打印陶瓷相关的知识差距，并将导致新型合成骨移植，这将为患有各种骨科疾病的患者提供更高的生活质量。科学星期六讲座和实践活动将向小学生、中学生、高中生和北卡罗来纳州自然科学博物馆的其他参观者传播该项目的成果。关于医用3D打印的最新进展的信息，包括该项目的结果，将通过在线研讨会系列传播给北卡罗来纳州的教师。技术总结：该项目将利用北卡罗来纳州州立大学和FDA关于新型生物材料的生物表征的独特能力，系统地评估制造、后处理(例如图案化和杀菌)以及对两种新型3D打印生物陶瓷的生物响应。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性质。例如，将使用扫描电子显微镜和原子力显微镜来评估3D打印生物陶瓷的表面特征的重复性和一致性。X射线衍射和X射线光电子能谱将分别用于检测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、细胞黏附动力学、细胞形态、细胞增殖和成骨分化研究，评估与应用相关的细胞(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。这项建议的独特之处在于，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。在这个学者常驻项目中获得的数据将与3D打印生物陶瓷医疗设备的开发和国际共识标准的改进相关，以促进3D打印医疗设备的监管决策。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.