Ammann Kaitlyn R, Li Maxwell, Hossainy Syed, Slepian Marvin J
Department of Biomedical Engineering, College of Engineering, The University of Arizona, Tucson, AZ 85721, United States.
Department of Bioengineering, College of Engineering, The University of California Berkeley, Berkeley, CA, 94720.
ACS Appl Bio Mater. 2019 Aug 19;2(8):3234-3244. doi: 10.1021/acsabm.9b00175. Epub 2019 May 2.
Implantable vascular devices typically interface with blood and vascular tissues. Physical properties of device materials and coatings, independent of chemical composition, can significantly influence cell responses and implant success. Here, we analyzed the effect of various polymer processing regimes, using a single implant polymer - poly(ε-caprolactone) (PCL), on vascular endothelial cell (EC), smooth muscle cell (SMC), and platelet response. PCL films were formed by varying three parameters: 1) formation method - solvent casting, melt pressing or spin coating; 2) molecular weight - 50 or 100 kDa; and 3) solvent type - dichloromethane (DCM) or tetrahydrofuran (THF). We quantified the relationship of polymer processing choice to surface roughness, wettability, and bulk stiffness; and to EC adhesion, SMC adhesion, and platelet activity state (PAS). Multiple regression analysis identified which processing method signficantly impacted (F-ratio>p-value; p<0.1) polymer physical properties and vascular cell interaction. Film formation method affected PCL roughness (R), wettability (°), and stiffness (MPa) with spin coating resulting in the most wettable (81.8±0.7°), and stiffest (1.12±0.07 MPa; p<0.001) polymer film; however, solvent cast films were the roughest (281±66nm). Molecular weight influenced wettability, with the highest wettability on 50 kDa films (79.7±0.7°; p<0.001) and DCM solvent films (83.0±1.0°; p<0.01). The multiple regression model confidently predicted (F-ratio=9.88; p=0.005) wettability from molecular weight (p=0.002) and film formation method (p=0.03); stiffness (F-ratio=4.21; p=0.05) also fit well tofilm formation method (p=0.02). Film formation method impacted SMC adhesion and platelet activity state, but not EC adhesion, with melt press PCL promoting the highest SMC adhesion (18000±1536 SMCs; p<0.05) and PAS (5.0±0.7 %PAS). The regression model confidently fit SMC adhesion (F-ratio=3.15; p=0.09) and PAS (F-ratio=5.30; p=0.05) to polymer processing choices, specifically film formation method (p<0.03). However, only SMC adhesion had a model that fit well (F-ratio=4.13; p=0.05) to the physical properties directly, specifically roughness and wettability (p<0.04).
可植入血管装置通常与血液和血管组织相互作用。装置材料和涂层的物理性质，与化学成分无关，会显著影响细胞反应和植入成功率。在此，我们分析了各种聚合物加工方式，使用单一植入聚合物——聚（ε-己内酯）（PCL），对血管内皮细胞（EC）、平滑肌细胞（SMC）和血小板反应的影响。通过改变三个参数形成PCL薄膜：1）形成方法——溶剂浇铸、熔融压制或旋涂；2）分子量——50或100 kDa；3）溶剂类型——二氯甲烷（DCM）或四氢呋喃（THF）。我们量化了聚合物加工选择与表面粗糙度、润湿性和本体刚度之间的关系；以及与EC黏附、SMC黏附及血小板活性状态（PAS）之间的关系。多元回归分析确定了哪种加工方法对聚合物物理性质和血管细胞相互作用有显著影响（F值>p值；p<0.1）。薄膜形成方法影响PCL的粗糙度（R）、润湿性（°）和刚度（MPa），旋涂法得到的聚合物薄膜润湿性最强（81.8±0.7°）且刚度最大（1.12±0.07 MPa；p<0.001）；然而，溶剂浇铸薄膜最粗糙（281±66nm）。分子量影响润湿性，50 kDa薄膜（79.7±0.7°；p<0.001）和DCM溶剂薄膜（83.0±1.0°；p<0.01）的润湿性最高。多元回归模型可靠地预测（F值=9.88；p=0.005）了由分子量（p=0.002）和薄膜形成方法（p=0.03）决定的润湿性；刚度（F值=4.21；p=0.05）也与薄膜形成方法（p=0.02）拟合良好。薄膜形成方法影响SMC黏附和血小板活性状态，但不影响EC黏附，熔融压制的PCL促进了最高的SMC黏附（18000±1536个SMC；p<0.05）和PAS（5.0±0.7 %PAS）。回归模型可靠地将SMC黏附（F值=3.15；p=0.09）和PAS（F值=5.30；p=0.05）与聚合物加工选择，特别是薄膜形成方法（p<0.03）进行了拟合。然而，只有SMC黏附具有一个与物理性质直接拟合良好的模型（F值=4.13；p=0.05），特别是粗糙度和润湿性（p<0.04）。
