Nature shows many examples of surfaces with extraordinary wettability, which can often be associated with particular air-trapping surface patterns. Here, robust non-wetting surfaces have been created by femtosecond laser ablation of polytetrafluoroethylene (PTFE). The laser-created surface structure resembles a forest of entangled fibers, which support structural superhydrophobicity even when the surface chemistry is changed by gold coating. SEM analysis showed that the degree of entanglement of hairs and the depth of the forest pattern correlates positively with accumulated laser fluence and can thus be influenced by altering various laser process parameters. The resulting fibrous surfaces exhibit a tremendous decrease in wettability compared to smooth PTFE surfaces; droplets impacting the virgin or gold coated PTFE forest do not wet the surface but bounce off. Exploratory bioadhesion experiments showed that the surfaces are truly air-trapping and do not support cell adhesion. Therewith, the created surfaces successfully mimic biological surfaces such as insect wings with robust anti-wetting behavior and potential for antiadhesive applications. In addition, the fabrication can be carried out in one process step, and our results clearly show the insensitivity of the resulting non-wetting behavior to variations in the process parameters, both of which make it a strong candidate for industrial applications.

Polylactide (PLA) is a promising biosourced and biodegradable polymer substitute for traditional petroleum-based products. Despite its recognized potential, its widespread adoption is restricted by its brittleness and low ductility and, thus, to enhance its material properties, plasticizers must be blended with PLA to lower the glass transition temperature (T g) and impart flexibility into the blend. As such, this work focused on the synthesis of a family of biosourced plasticizers for applications in flexible food packaging using glycerol, succinic anhydride, and alcohols of varying chain lengths. The effect of the chemical structure on plasticization performance, migration, blend morphology, and toxicity was evaluated and compared to the commercial plasticizer acetyl tributyl citrate. Plasticizer/PLA blends were prepared using solvent-casting as well as melt-mixing to produce thin films and bulk specimens. At loadings of 20 wt %, improved flexibility (up to 435% elongation) was observed in films with the glycerol plasticizers relative to neat PLA (6% elongation), while T g’s were reduced by up to 45 °C from that of neat PLA (T g ∼ 60 °C). Phase morphologies evaluated with scanning electron microscopy showed good incorporation of the plasticizers into the PLA matrix. Leaching behavior of the plasticized blends was evaluated in different food simulants and showed that plasticizers composed of branched or longer alkyl chains produced two- to sixfold lower migration rates compared to those with short alkyl chains. Finally, plasticizer candidates were shown to be nontoxic and did not impact HepG2 cell viability over a period of 7 days in an in vitro mammalian cell assay.

Transplantation of hydrogel-encapsulated pancreatic islets is a promising long-term treatment for type 1 diabetes that restores blood glucose regulation while providing graft immunoprotection. Most human-scale islet encapsulation devices that rely solely on diffusion fail to provide sufficient surface area to meet islet oxygen demands. Perfused macroencapsulation devices use blood flow to mitigate oxygen limitations but increase the complexity of blood-device interactions. Here we describe a human-scale in vitro perfusion system to study hemocompatibility and performance of islet-like cell clusters (ILCs) in alginate hydrogel. A cylindrical perfusion device was designed for multi-day culture without leakage, contamination, or flow occlusion. Rat blood perfusion was assessed for prothrombin time and international normalized ratio and demonstrated no significant change in clotting time. Ex vivo perfusion performed with rats showed patency of the device for over 100 min using Doppler ultrasound imaging. PET-CT imaging of the device successfully visualized metabolically active mouse insulinoma 6 ILCs. ILCs cultured for 7 days under static conditions exhibited abnormal morphology and increased activated caspase-3 staining when compared with the perfused device. These findings reinforce the need for convective transport in macroencapsulation strategies and offer a robust and versatile in vitro system to better inform preclinical design.

Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 μM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 μM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 μM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 μM. A higher simvastatin concentration of 10 μM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.

Islet encapsulation devices serve to deliver pancreatic beta cells to type 1 diabetic patients without the need for chronic immunosuppression. However, clinical translation is hampered by mass transport limitations causing graft hypoxia. This is exacerbated in devices relying only on passive diffusion for oxygenation. Here, we describe the application of a cylindrical in vitro perfusion system to study oxygen effects on islet-like clusters immobilized in alginate hydrogel. Mouse insulinoma 6 islet-like clusters were generated using microwell plates and characterized with respect to size distribution, viability, and oxygen consumption rate to determine an appropriate seeding density for perfusion studies. Immobilized clusters were perfused through a central channel at different oxygen tensions. Analysis of histological staining indicated the distribution of viable clusters was severely limited to near the perfusion channel at low oxygen tensions, while the distribution was broadest at normoxia. The results agreed with a 3D computational model designed to simulate the oxygen distribution within the perfusion device. Further simulations were generated to predict device performance with human islets under in vitro and in vivo conditions. The combination of experimental and computational findings suggest that a multichannel perfusion strategy could support in vivo viability and function of a therapeutic islet dose.