NSF/FDA SIR: Fabrication and Evaluation of Bioactive and Biodegradable 3D Printed Polymer Scaffolds

摘要：这项由美国阿克伦大学材料研究部生物材料项目授予的NSF/FDA驻校学者项目旨在优化一组将被包裹在治疗药物中的聚合物底物。该项目将研究如何将治疗纳入3D打印材料将影响其打印过程和打印结构。3D打印吸引了科学家和非科学家的想象力。现在可以想象，未来的制造协议将包括3D打印作为制造工程和医疗产品的一种方法。3D打印的强大功能与医疗产品更加相关，在医疗产品中，有可能创建个性化的合成“器官”来取代受损或患病的器官。这种装置也可用于以个性化剂量递送治疗药物。然而，为了便于将这种3D打印设备转化为临床，需要解决几个方面的问题。此外，这些研究还将检查这些聚合物结构的降解和治疗药物释放的速度。这些研究将在FDA使用标准化协议进行，这将与未来FDA对3D打印支架的监管检查相关。此外，该奖项将为研究生提供培训机会，并为他们在工程和科学领域的职业生涯做好准备。该奖项还将使本科生和高中生接触3D打印领域。技术摘要：3D打印作为一种制造个性化医疗支架的有效方法正在迅速兴起。3D打印医疗设备解决了几个所需的植入物特征，例如需要打印不规则的特征形状和大小，需要植入物孔隙度以及合并或封装生物活性分子的能力。该领域的一个关键需求是聚合物材料具有正确的性能集，使其能够打印并融入生理环境。此外，为了在生物环境中实现合成材料的最佳整合，通常需要用生物活性分子封装它们。打印后，它们将被交联以“固定”打印的支架。这种粘弹性聚酯将被地塞米松（一种抗炎皮质类固醇）包裹。或者，聚酯将被骨形态发生蛋白包裹。早期的研究已经证明了这些疗法的临床相关性。该奖项将研究这些治疗方法对打印过程和打印结构的影响，打印结构的可重复性、生物相容性和生物降解性。此外，本研究还将研究包封的生物活性物质的释放特征。用于评估这些支架的方法将与FDA合作进行，这些研究有望帮助FDA建立分析和评估3D打印支架的一般方案。

Non-technical Abstract: This NSF/FDA Scholar-in-Residence program award by the Biomaterials Program in the Division of Materials Research to University of Akron is aimed towards the optimization of a set of polymeric substrates that will be encapsulated with therapeutics. This project will examine how the incorporation of therapeutics within the 3D printing materials will affect their printing process and the printed structures. 3D printing has caught the imagination of scientists and non-scientists alike. It is now conceivable that future manufacturing protocols will include 3D printing as a method to manufacture engineering and medical products. The power of 3D printing becomes all the more relevant for medical products, where it may be possible to create personalized synthetic 'organs' to replace damaged or diseased organs. Such devices may also be used to deliver therapeutics at personalized dosages. However to facilitate the translation of such 3D printed devices to the clinic, several aspects need to be addressed. In addition, these studies will also examine the degradation of these polymeric structures and the rates at which the therapeutic is released. These studies will be carried out at FDA using standardized protocols that will be relevant for future FDA regulatory examinations of 3D printed scaffolds. In addition, the award will provide training opportunities to graduate students and will prepare them for careers in engineering and science. The award will also expose undergraduate and high school students to the field of 3D printing. Technical Abstract: 3D printing is rapidly emerging as an efficient method for the fabrication of personalized medical scaffolds. 3D printing medical devices addresses several desired implant features such as the need to print irregular feature shapes and sizes and the need for implant porosity and the ability to incorporate or encapsulate bioactive molecules. A critical need in this area is for polymeric materials having the right set of properties that enable their printing and integration into the physiological environment. In addition, to enable optimal integration of synthetic materials in a biological environment, it is often necessary to encapsulate them with bioactive molecules. Upon printing they will be cross-linked to 'fix' the printed scaffolds. Such viscoelastic polyesters will be encapsulated with dexamethasone, an anti-inflammatory corticosteroid. Alternatively, the polyesters will be encapsulated with bone morphogenetic proteins. Earlier studies have demonstrated clinical relevance of these therapeutics. This award will examine the effect of such therapeutics on the printing process and on the printed structures, the reproducibility, biocompatibility and biodegradation of the printed structures. In addition, this study will also examine the release profile of the encapsulated bioactive materials. The methodologies adopted for the evaluation of these scaffolds will be carried out in collaboration with the FDA, and these studies are expected to help FDA in establishing protocols for analysis and evaluation of 3D printed scaffolds in general.