Hydrogel Inverse Replicas of Breath Figures Exhibit Superoleophobicity Due to Patterned Surface Roughness.

The wetting behavior of a surface depends on both its surface chemistry and the characteristics of surface morphology and topography. Adding structure to a flat hydrophobic or oleophobic surface increases the effective contact angle and thus the hydrophobicity or oleophobicity of the surface, as exemplified by the lotus leaf analogy. We describe a simple strategy to introduce micropatterned roughness on surfaces of soft materials, utilizing the template of hexagonally packed pores of breath figures as molds. The generated inverse replicas represent micron scale patterned beadlike protrusions on hydrogel surfaces. This added roughness imparts superoleophobic properties (contact angle of the order of 150° and greater) to an inherently oleophobic flat hydrogel surface, when submerged. The introduced pattern on the hydrogel surface changes morphology as it swells in water to resemble morphologies remarkably analogous to the compound eye. Analysis of the wetting behavior using the Cassie-Baxter approximation leads to estimation of the contact angle in the superoleophobic regime and in agreement with the experimental value.

Effect of Two Novel Sustained-Release Drug Delivery Systems on Bleb Fibrosis: An In Vivo Glaucoma Drainage Device Study in a Rabbit Model.

PURPOSE: To evaluate two drug delivery systems, a nonbiodegradable poly(2-hydroxyethyl methacrylate) (P[HEMA]) system with mitomycin C (MMC) and a biodegradable poly(lactic-co-glycolic acid) (PLGA) system with 5-fluorouracil (5-FU) with and without MMC for their ability to reduce fibrosis when attached to an Ahmed glaucoma valve (AGV) and implanted in a rabbit model. METHODS: New Zealand albino rabbits (48) were divided into six equal groups, and AGVs, modified as described below, were implanted in the right eye of each rabbit. The groups included (1) PLGA alone; (2) P(HEMA) plus MMC (6.5 µg); (3) PLGA plus 5-FU (0.45 mg); (4) PLGA plus 5-FU (1.35 mg); (5) PLGA plus 5-FU and MMC (0.45 mg and 0.65 µg, respectively); (6) PLGA plus 5-FU and MMC (1.35 mg and 0.65 µg, respectively). The rabbits were followed for 3 months prior to euthanasia. RESULTS: The bleb wall thickness was significantly less in groups 2, 5, and 6 compared to the rest. At 3 months, the PLGA polymer had completely disappeared, while the P(HEMA) polymer remained intact. There were no statistical differences in the degree of clinically graded conjunctival injection, histologic inflammation, or histologic fibrosis among the six groups. CONCLUSIONS: We successfully created a sustained-release drug delivery system that decreased the postoperative fibrosis using both a nonbiodegradable P(HEMA) polymer and a biodegradable (PLGA) polymer. Both systems appear to work equally well with no side effects. TRANSLATIONAL RELEVANCE: These results are supportive of the antifibrotic effect of the slow-release drug delivery system following glaucoma drainage device implantation, thus paving the way for human pilot studies.

Novel "breath figure"-based synthetic PLGA matrices for in vitro modeling of mammary morphogenesis and assessing chemotherapeutic response.

Biodegradable poly(lactic-co-glycolic acid) (PLGA) porous films are developed to support mammary cell growth and function. Such porous polymer matrices of PLGA are generated using the easily implemented water-templating "breath-figure" technique that allows water droplets to penetrate the nascent polymer films to create a rough porous polymer film. Such breath figure-based micropatterned porous films show higher epithelial differentiation and growth than the corresponding flat 2D films, and represent the first instance of using them for tissue culture. Specifically, the breath figure morphology supports robust acinar growth with almost double the number of lobular-alveolar units compared to the 2D cultures. Gene profile analysis indicates that the cells grown on porous polymer films show enhanced expressions of mammary differentiation genes (GATA3, EMA, and INTEGB4) but lower the expression of mesenchymal gene (CALLA). Hormonal stimulation of these cultures dramatically increases expression of progenitor marker gene Notch1. Importantly, cells grown on porous PLGA films exhibit an enhanced resistance to doxorubicin treatment in comparison to 2D cultures. Breath-figure PLGA films show promise in mimicking in vivo mammary functions and can potentially be used to screen chemotherapeutic drugs. The simplicity and ease of fabrication of these polymer films is especially appealing to the development of effective biomaterials to support cell culture and differentiation.

A novel antiproliferative drug coating for glaucoma drainage devices.

PURPOSE: The implantation of a glaucoma drainage device (GDD) is often necessary for intractable cases of glaucoma. Currently, the success rate of GDD implants is relatively low because fibrosis that develops during the wound-healing process ultimately blocks fluid drainage. We describe herein a novel porous coating for Ahmed glaucoma valves based on biodegradable poly(lactic-co-glycolic acid) (PLGA). MATERIALS AND METHODS: Thin films of PLGA were fabricated using a spin-coating technique. The procedure led to an asymmetric pore structure that was exploited to control the rate of dissolution. Double-layered porous films were constructed to achieve continuous drug release. A cell culture system was used to test the efficacy of these coatings. RESULTS: Double-layered films were manufactured to provide a burst of mitomycin C (MMC) release followed by a slow release of 5-fluorouracil (5-FU), which together prevented fibrosis over the most active period of postoperative wound healing (0 to 28 d). Double-layered films containing 5-FU only in the bottom layer showed a 3- to 5-day delay in drug release, followed by a sharp increase that continued for ~28 days. MMC was stable only when surface-loaded, and this drug was therefore surface-loaded onto the top PLGA layer to provide a continuous release of antifibrotics over the wound-healing period. CONCLUSIONS: The combined use of both MMC and 5-FU in a biodegradable device inhibits cell proliferation in a tissue culture model and has the potential to reduce fibrosis and increase the success rate of GDD implants. The design is simple and can be scaled for commercial production.

In vitro degradation and release characteristics of spin coated thin films of PLGA with a "breath figure" morphology.

Poly (lactic-co-glycolic acid) (PLGA) coatings on implant materials are widely used in controlled drug delivery applications. Typically, such coatings are made with non-porous films. Here, we have synthesized a thin PLGA film coating with a highly ordered microporous structure using a simple and inexpensive water templating "breath figure" technique. A single stage process combining spin coating and breath figure process was used to obtain drug incorporated porous thin films. The films were characterized by scanning electron microscope (SEM) to observe the surface and bulk features of porosity and also, degradation pattern of the films. Moreover, the effect of addition of small amount of poly (ethylene glycol) (PEG) into PLGA was characterized. SEM analysis revealed an ordered array of ~2 µm sized pores on the surface with the average film thickness measured to be 20 µm. The incorporation of hydrophilic poly (ethylene glycol) (PEG) enhances pore structure uniformity and facilitates ingress of water into the structure. A five week in vitro degradation study showed a gradual deterioration of the breath figure pores. During the course of degradation, the surface pore structure deteriorates to initially flatten the surface. This is followed by the formation of new pinprick pores that eventually grow into a macroporous film prior to film breakup. Salicylic acid (highly water soluble) and Ibuprofen (sparingly water soluble) were chosen as model drug compounds to characterize release rates, which are higher in films of the breath figure morphology rather than in non-porous films. The results are of significance in the design of biodegradable films used as coatings to modulate delivery.