Jain Tanmay, Saylor David, Piard Charlotte, Liu Qianhui, Patel Viraj, Kaushal Rahul, Choi Jae-Won, Fisher John, Isayeva Irada, Joy Abraham
Department of Polymer Science, The University of Akron, 170 University Avenue, Akron, Ohio 44325, United States.
Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, United States.
ACS Biomater Sci Eng. 2019 Feb 11;5(2):846-858. doi: 10.1021/acsbiomaterials.8b00964. Epub 2019 Jan 2.
Three-dimensional (3D) printing has enabled benchtop fabrication of customized bioengineered constructs with intricate architectures. Various approaches are being explored to enable optimum integration of such constructs into the physiological environment including addition of bioactive fillers. In this work, we incorporated a corticosteroid drug, dexamethasone (Dex), in a low modulus polyester (SC5050) and examined the effect of Dex incorporation on solvent-, initiator-, and monomer-free pneumatic extrusion-based 3D printing of the polymer. Dex-SC5050 interactions were characterized by plotting thermodynamic binary phase diagrams based on the Flory-Huggins theory. The effect of Dex composition on the 3D printability of the SC5050 polyester was examined by rheological characterization and by image analysis of each layer of the 3D printed scaffolds. The drug release and the degradation of the polymer from the 3D printed scaffolds was used to analyze the effect of Dex composition on the performance of the 3D printed scaffolds. We found that Dex was insoluble in SC5050 polyester at relevant 3D printing temperatures and the insoluble drug particles physically reinforced the polymer, increasing the viscosity and the shear modulus of the base polymer. In addition, the reinforcing effect improved the shape fidelity of the printed filaments and the overall quality of the scaffolds. The Dex particles demonstrated a two-phase release, with an initial burst release and a slower sustained release of drug under in vitro conditions. To investigate preliminary host response of the 3D printed SC5050 scaffolds for tissue engineering applications, the printed scaffolds were implanted subcutaneously in Sprague-Dawley rats for 6 weeks and examined for fibrous tissue formation, infiltration of cells, and vascularization into the pores of the scaffolds.
三维(3D)打印技术已实现了具有复杂结构的定制化生物工程构建体的台式制造。人们正在探索各种方法,以使此类构建体能够最佳地整合到生理环境中,包括添加生物活性填料。在这项工作中,我们将一种皮质类固醇药物地塞米松(Dex)掺入低模量聚酯(SC5050)中,并研究了掺入Dex对该聚合物基于无溶剂、无引发剂和无单体的气动挤出3D打印的影响。基于弗洛里 - 哈金斯理论绘制热力学二元相图,对Dex - SC5050的相互作用进行了表征。通过流变学表征以及对3D打印支架各层的图像分析,研究了Dex组成对SC5050聚酯3D可打印性的影响。利用3D打印支架中聚合物的药物释放和降解情况,分析Dex组成对3D打印支架性能的影响。我们发现,在相关的3D打印温度下,Dex不溶于SC5050聚酯,不溶性药物颗粒对聚合物起到物理增强作用,提高了基础聚合物的粘度和剪切模量。此外,这种增强作用改善了打印细丝的形状保真度和支架的整体质量。Dex颗粒呈现出两相释放,在体外条件下,药物最初会有一个突发释放,随后是较慢的持续释放。为了研究用于组织工程应用的3D打印SC5050支架的初步宿主反应,将打印好的支架皮下植入Sprague - Dawley大鼠体内6周,然后检查支架孔隙内的纤维组织形成、细胞浸润和血管化情况。