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.

We have prepared 3D superhydrophobic materials from biocompatible building blocks, where air acts as a barrier component in a porous electrospun mesh to control the rate at which drug is released. Specifically, we fabricated poly(ε-caprolactone) electrospun meshes containing poly(glycerol monostearate-co-ε-caprolactone) as a hydrophobic polymer dopant, which results in high apparent contact angle meshes. We demonstrate that the apparent contact angle of these meshes dictates the rate at which water penetrates into the porous network and displaces entrapped air. Addition of a model bioactive agent (SN-38) shows a release rate with a striking dependence on apparent contact angle which can be explained by this displacement of air within the electrospun meshes. We further show that porous, higher surface area electrospun meshes can be prepared to release more slowly than control non-porous constructs. Finally, the entrapped air layer within superhydrophobic meshes is shown to be robust in the presence of serum, where drug loaded meshes are efficacious against cancer cells in vitro for >60 days, thus demonstrating applicability for long-term drug delivery.

Adsorption of lysozyme (Lys), human serum albumin (HSA), and immunoglobulin G (IgG) to anion- and cation-exchange resins is dominated by electrostatic interactions between protein and adsorbent. The solution-depletion method of measuring adsorption shows, however, that these proteins do not irreversibly adsorb to ion-exchange surfaces, even when the charge disparity between adsorbent and protein inferred from protein pI is large. Net-positively-charged Lys (pI=11) and net-negatively-charged HSA (pI=5.5) adsorb so strongly to sulfopropyl sepharose (SP; a negatively-charged, strong cation-exchange resin, -0.22 mmol/mL exchange capacity) that both resist displacement by net-neutral IgG (pI=7.0) in simultaneous adsorption competition experiments. By contrast, IgG readily displaces both Lys and HSA adsorbed either to quaternary ammonium sepharose (Q; a positively-charged, strong anion exchanger, +0.22 mmol/mL exchange capacity) or to octadecyl sepharose (ODS; a neutral hydrophobic resin, 0 mmol/mL exchange capacity). Thus it is concluded that adsorption results do not sensibly correlate with protein pI and that pI is actually a rather poor predictor of affinity for ion-exchange surfaces. Adsorption of Lys, HSA, and IgG to ion-exchange resins from stagnant solution leads to adsorbed multi-layers, into or onto which IgG adsorbs in adsorption competition experiments. Comparison of adsorption to ion-exchange resins and neutral ODS leads to the conclusion that the apparent standard free-energy of adsorption Delta Gads( degrees ) of Lys, HSA, and IgG is not large in comparison to thermal energy due to energy-compensating interactions between water, protein, and ion-exchange surfaces that leaves a small net Delta Gads( degrees ). Thus water is found to control protein adsorption to a full range of substratum types spanning hydrophobic (poorly water wettable) surfaces, hydrophilic surfaces bearing relatively-weak Lewis acid/base functionalities that wet with (hydrogen bond to) water but do not exhibit ion-exchange properties, and surfaces with strong Lewis acid/base functional groups that exhibit ion-exchange properties in the conventional chemistry sense of ion-exchange.

In this work we expand upon a recently reported local drug delivery device, where air is used as a degradable component of our material to control drug release (J. Am. Chem. Soc. 2012, 134, 2016-2019). We consider its potential use as a drug loaded strip to provide both mechanical stability to the anastomosis, and as a means to release drug locally over prolonged periods for prevention of locoregional recurrence in colorectal cancer. Specifically, we electrospun poly(ε-caprolactone) (PCL) with the hydrophobic polymer dopant poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) and used the resultant mesh to control the release of two anticancer drugs (CPT-11 and SN-38). The increase in mesh hydrophobicity with PGC-C18 addition slows drug release both by the traditional means of drug diffusion, as well as by increasing the stability of the entrapped air layer to delay drug release. We demonstrate that superhydrophobic meshes have mechanical properties appropriate for surgical buttressing of the anastomosis, permit non-invasive assessment of mesh location and documentation of drug release via ultrasound, and release chemotherapy over a prolonged period of time (>90 days) resulting in significant tumor cytotoxicity against a human colorectal cell line (HT-29).