Superhydrophobic surfaces are actively studied across a wide range of applications and industries, and are now finding increased use in the biomedical arena as substrates to control protein adsorption, cellular interaction, and bacterial growth, as well as platforms for drug delivery devices and for diagnostic tools. The commonality in the design of these materials is to create a stable or metastable air state at the material surface, which lends itself to a number of unique properties. These activities are catalyzing the development of new materials, applications, and fabrication techniques, as well as collaborations across material science, chemistry, engineering, and medicine given the interdisciplinary nature of this work. The review begins with a discussion of superhydrophobicity, and then explores biomedical applications that are utilizing superhydrophobicity in depth including material selection characteristics, in vitro performance, and in vivo performance. General trends are offered for each application in addition to discussion of conflicting data in the literature, and the review concludes with the authors’ future perspectives on the utility of superhydrophobic surfaces for biomedical applications.

Superhydrophobic, porous, 3D materials composed of poly( ε -caprolactone) (PCL) and the hydrophobic polymer dopant poly(glycerol monostearate-co- ε -caprolactone) (PGC-C18) are fabricated using the electrospinning technique. These 3D materials are distinct from 2D superhydrophobic surfaces, with maintenance of air at the surface as well as within the bulk of the material. These superhydrophobic materials float in water, and when held underwater and pressed, an air bubble is released and will rise to the surface. By changing the PGC-C18 doping concentration in the meshes and/or the fiber size from the micro- to nanoscale, the long-term stability of the entrapped air layer is controlled. The rate of water infiltration into the meshes, and the resulting displacement of the entrapped air, is quantitatively measured using X-ray computed tomography. The properties of the meshes are further probed using surfactants and solvents of different surface tensions. Finally, the application of hydraulic pressure is used to quantify the breakthrough pressure to wet the meshes. The tools for fabrication and analysis of these superhydrophobic materials as well as the ability to control the robustness of the entrapped air layer are highly desirable for a number of existing and emerging applications.

Layered superhydrophobic electrospun meshes composed of poly(ε-caprolactone) (PCL) and poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) are described as a local source of chemotherapeutic delivery. Specifically, the chemotherapeutic agent SN-38 is incorporated into a central ‘core’ layer, between two ‘shield’ layers of mesh without drug. This mesh is resistant to wetting of the surface and throughout the bulk due to the pronounced hydrophobicity imparted by the high roughness of a hydrophobic polymer, PGC-C18. In serum solution, these meshes exhibit slow initial drug release over 10 days corresponding to media infiltrating the shield layer, followed by steady release over >30 days, as the drug-loaded core layer is wetted. This sequence of events is supported by X-ray computed tomography imaging of a contrast agent solution infiltrating the mesh. In vitro cytotoxicity data collected with Lewis Lung Carcinoma (LLC) cells are consistent with this release profile, remaining cytotoxic for over 20 days, longer than the unlayered version. Finally, after subcutaneous implantation in rats, histology of meshes with and without drug demonstrated good integration and lack of adverse reaction over 28 days. The drug release rates, robust superhydrophobicity, in vitro cytotoxicity of SN-38 loaded meshes, and compatibility provide key design parameters for the development of an implantable chemotherapeutic-loaded device for the prevention of local lung cancer recurrence following surgical resection.

Real-time, accurate assessment of islet viability is critical for avoiding transplantation of nontherapeutic preparations. Measurements of the intracellular ADP/ATP ratio have been recently proposed as useful prospective estimates of islet cell viability and potency. However, dead cells may be rapidly depleted of both ATP and ADP, which would render the ratio incapable of accounting for dead cells. Since the DNA of dead cells is expected to remain stable over prolonged periods of time (days), we hypothesized that use of the ATP/DNA ratio would take into account dead cells and may be a better indicator of islet cell viability than the ADP/ATP ratio. We tested this hypothesis using mixtures of healthy and lethally heat-treated (HT) rat insulinoma cells and human islets. Measurements of ATP/DNA and ADP/ATP from the known mixtures of healthy and HT cells and islets were used to evaluate how well these parameters correlated with viability. The results indicated that ATP and ADP were rapidly (within 1 hour) depleted in HT cells. The fraction of HT cells in a mixture correlated linearly with the ATP/DNA ratio, whereas the ADP/ADP ratio was highly scattered, remaining effectively unchanged. Despite similar limitations in both ADP/ADP and ATP/ DNA ratios, in that ATP levels may fluctuate significantly and reversibly with metabolic stress, the results indicated that ATP/DNA was a better measure of islet viability than the ADP/ATP ratio.Islet cell transplantation is emerging as a promising therapy for the treatment of type 1 diabetes. [1][2][3][4][5] Despite recent advances, the transplantation of islets poses a unique challenge with respect to achieving a consistent clinical outcome. Part of this challenge is being able to reliably and rapidly assess clinical islet quality through the quantification of viability and function before transplantation. Current viability assays are limited in their ability to accurately predict transplantation outcomes in vivo. 6 Consequently, to improve the clinical islet transplantation outcomes, it is imperative to develop more accurate viability assays.A proposed method to assess islet viability and potency before transplantation is quantification of the ADP/ATP ratio. 6 -10 This ratio has been specifically applied in discriminating islet preparations that are suitable for clinical transplantation from those that are not. 6 However, this application may be problematic under certain conditions. Intracellular ADP and ATP levels fluctuate rapidly because these high-energy phosphate molecules are rapidly produced and consumed in many intracellular biochemical reactions. It is widely known that viable cells turn over entire ATP stores on the order of minutes, and that dead cells are incapable of replenishing To better account for dead cells and to more accurately assess the viability of an islet preparation, we suggest the use of an ATP/DNA ratio. DNA does not degrade as rapidly as ADP or ATP in a dead cell. Therefore, using direct measurements of DNA, dead cells in an islet preparation...

Introduction Despite significant progress in the last decade, islet transplantation remains an experimental therapy for a limited number of patients with type 1 diabetes. Tissue-engineered approaches may provide promising alternatives to the current clinical protocol and would benefit greatly from concurrent development of graft quality assessment techniques. This study was designed to evaluate whether viability of tissue-engineered islet grafts can be assessed using fluorine magnetic resonance spectroscopy (19F-MRS), by the noninvasive measurement of oxygen partial pressure (pO2) and the subsequent calculation of islet oxygen consumption rate (OCR). Methods Scaffolds composed of porcine plasma were seeded with human islets and perfluorodecalin. Each graft was covered with the same volume of culture media in a Petri dish. Four scaffolds were seeded with various numbers (0–8000) of islet equivalents (IE) aliquoted from the same preparation. After randomizing run order, grafts were examined by 19F-MRS at 37°C using a 5T spectrometer and a single-loop surface coil placed underneath. A standard inversion recovery sequence was used to obtain characteristic 19F spin-lattice relaxation times (T1), which were converted to steady-state average pO2 estimates using a previously determined linear calibration (R2 = 1.000). Each condition was assessed using replicate 19F-MRS measurements (n = 6–8). Results Grafts exhibited IE dose-dependent increases in T1 and decreases in pO2 estimates. From the difference between scaffold pO2 estimates and ambient pO2, the islet preparation OCR was calculated to be 95 ± 12 (mean ± standard error of the mean) nmol/(min · mg DNA) using theoretical modeling. This value compared well with OCR values measured using established methods for human islet preparations. Conclusions 19F-MRS can be used for noninvasive pre- and possibly posttransplant assessment of tissue-engineered islet graft viability by estimating the amount of viable, oxygen-consuming tissue in a scaffold.