Streamlined Specimen Purification for Rapid COVID-19 Diagnosis Using Positively Charged Polymer Thin Film-Coated Surfaces and Chamber Digital PCR.

The ongoing coronavirus disease 2019 (COVID-19) pandemic demands rapid and straightforward diagnostic tools to prevent early-stage viral transmission. Although nasopharyngeal swabs are a widely used patient sample collection method for diagnosing COVID-19, using these samples for diagnosis without RNA extraction increases the risk of obtaining false-positive and -negative results. Thus, multiple purification steps are necessary, which are time-consuming, generate significant waste, and result in substantial sample loss. To address these issues, we developed surface-modified polymerase chain reaction (PCR) tubes using the tertiary aminated polymer poly(2-dimethylaminomethylstyrene) (pDMAMS) via initiated chemical vapor deposition. Introducing the clinical samples into the pDMAMS-coated tubes resulted in approximately 100% RNA capture efficiency within 25 min, which occurred through electrostatic interactions between the positively charged pDMAMS surface and the negatively charged RNA. The captured RNA is then detected via chamber digital PCR, enabling a sensitive, accurate, and rapid diagnosis. Our platform provides a simple and efficient RNA extraction and detection strategy that allows detection from 22 nasopharyngeal swabs and 21 saliva specimens with 0% false negatives. The proposed method can facilitate the diagnosis of COVID-19 and contribute to the prevention of early-stage transmission.

Engineering of Surface Energy of Cell-Culture Platform to Enhance the Growth and Differentiation of Dendritic Cells via Vapor-Phase Synthesized Functional Polymer Films.

Although the dendritic cell (DC)-based modulation of immune responses has emerged as a promising therapeutic strategy for tumors, infections, and autoimmune diseases, basic research and therapeutic applications of DCs are hampered by expensive growth factors and sophisticated culture procedures. Furthermore, the platform to drive the differentiation of a certain DC subset without any additional biochemical manipulations has not yet been developed. Here, five types of polymer films with different hydrophobicity via an initiated chemical vapor deposition (iCVD) process to modulate the interactions related to cell-substrate adhesion are introduced. Especially, poly(cyclohexyl methacrylate) (pCHMA) substantially enhances the expansion and differentiation of conventional type 1 DCs (cDC1s), the prime DC subset for antigen cross-presentation, and CD8+ T cell activation, by 4.8-fold compared to the conventional protocol. The cDC1s generated from the pCHMA-coated plates retain the bona fide DC functions including the expression of co-stimulatory molecules, cytokine secretion, antigen uptake and processing, T cell activation, and induction of antitumor immune responses. To the authors' knowledge, this is the first report highlighting that the modulation of surface hydrophobicity of the culture plate can be an incisive approach to construct an advanced DC culture platform with high efficiency, which potentially facilitates basic research and the development of immunotherapy employing DCs.

High-Fidelity, Sub-5 nm Patterns from High-χ Block Copolymer Films with Vapor-Deposited Ultrathin, Cross-Linked Surface-Modification Layers.

Despite their capability, sub-10 nm periodic nano-patterns formed by strongly segregating block copolymer (BCP) thin films cannot be easily oriented perpendicular to the substrate due to the huge surface energy differences of the constituent blocks. To produce perpendicular nano-patterns, the interfacial energies of both the substrate and free interfaces should be controlled precisely to induce non-preferential wetting. Unfortunately, high-performance surface modification layers are challenging to design, and different kinds of surface modification methods must be devised respectively for each neutral layer and top coat. Furthermore, conventional approaches, largely based on spin-coating processes, are highly prone to defect formation and may readily cause dewetting at sub-10 nm thickness. To date, these obstacles have hampered the development of high-fidelity, sub-5 nm BCP patterns. Herein, an all-vapor phase deposition approach initiated chemical vapor deposition is demonstrated to form 9-nm-thick, uniform neutral bottom layer and top coat with exquisite control of composition and thickness. These layers are employed in BCP films to produce perpendicular cylinders with a diameter of ≈4 nm that propagate throughout a BCP thickness of up to ≈60 nm, corresponding to five natural domain spacings of the BCP. Such a robust approach will serve as an advancement for the reliable generation of sub-10 nm nano-patterns.

Polymer Analog Memristive Synapse with Atomic-Scale Conductive Filament for Flexible Neuromorphic Computing System.

With the advent of artificial intelligence (AI), memristors have received significant interest as a synaptic building block for neuromorphic systems, where each synaptic memristor should operate in an analog fashion, exhibiting multilevel accessible conductance states. Here, we demonstrate that the transition of the operation mode in poly(1,3,5-trivinyl-1,3,5-trimethyl cyclotrisiloxane) (pV3D3)-based flexible memristor from conventional binary to synaptic analog switching can be achieved simply by reducing the size of the formed filament. With the quantized conductance states observed in the flexible pV3D3 memristor, analog potentiation and depression characteristics of the memristive synapse are obtained through the growth of atomically thin Cu filament and lateral dissolution of the filament via dominant electric field effect, respectively. The face classification capability of our memristor is evaluated via simulation using an artificial neural network consisting of pV3D3 memristor synapses. These results will encourage the development of soft neuromorphic intelligent systems.

Hydrogel-laden paper scaffold system for origami-based tissue engineering.

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

reliable Synthesis of Monodisperse Microparticles: Prevention of Oxygen Diffusion and Organic Solvents Using Conformal Polymeric Coating onto Poly(dimethylsiloxane) Micromold.

An effective polymeric thin film deposited by initiated chemical vapor deposition (iCVD) process was presented and its application as a barrier film on the PDMS micromold blocking the penetration of oxygen and organic solvents was investigated. With this barrier film, we were able to synthesize monodisperse polymeric particles of sizes down to 3 µm, which has been reported to be extremely challenging with bare PDMS micromold. The polymeric barrier film on the PDMS micromold enabled this successful synthesis of microparticles by effectively blocking the diffusion of oxygen, which is a well-known radical quencher in radical polymerization, through the PDMS micromold. Furthermore, the iCVD barrier film substantially decreased the penetration of various organic solvents such as acetone, tert-butanol, PDMS oil, and decane as well as organic substances including fluorescent molecules like rhodamine B and fluorescein isothiocyanate (FITC). Therefore, the polymeric barrier film coated on PDMS micromold via iCVD process will broaden the application of PDMS to microfluidic area for the synthesis of smaller microparticles with various organic substances.

Heparin-mediated electrostatic immobilization of bFGF via functional polymer films for enhanced self-renewal of human neural stem cells.

Preserving the self-renewal capability of undifferentiated human neural stem cells (hNSCs) is one of the crucial prerequisites for efficient hNSC-based regenerative medicine. Considering that basic fibroblast growth factor (bFGF) is one of the key contributing factors in maintaining the self-renewal property of hNSCs, the bioactivity and stability of bFGF in the hNSC culture should be regulated carefully. In this study, we developed a functional polymer film of poly(glycidyl methacrylate (GMA)-co-N,N-dimethylaminoethyl methacrylate (DMAEMA)) (coGD, or p(GMA-co-DMAEMA)) via initiated chemical vapor deposition (iCVD), which facilitated a stable, electrostatic adsorption of heparin and subsequent immobilization of bFGF. The bFGF-immobilized coGD surface substantially enhanced the proliferation rate and neurosphere forming ability of hNSCs compared to tissue culture plate (TCP). The expression of the stemness markers of hNSCs such as NESTIN and SOX-2 was also upregulated prominently on the coGD surface. Also, the hNSCs cultured on the coGD surface showed enhanced neurogenesis upon spontaneous differentiation. The immobilized bFGF on the coGD surface stimulated the expression of bFGF receptors and subsequently activated the mitogen-activated protein kinase (MAPK) pathway, attributed to the increase in self-renewal property of hNSCs. Our results indicate that the coGD surface allowed in situ heparin-mediated bFGF immobilization, which served as a robust platform to generate hNSC neurospheres with enhanced self-renewal and differentiation capabilities and thereby will prompt an advance in the field of therapeutics of neurodegenerative diseases.

Three-Dimensional Spheroid Culture on Polymer-Coated Surface Potentiate Stem Cell Functions via Enhanced Cell-Extracellular Matrix Interactions.

The aggregation of mesenchymal stem cells (MSCs) into three-dimensional (3D) spheroids has emerged as a promising therapeutic candidate for the treatment of a variety of diseases. In spite of the numerous 3D culture methods suggested recently for MSC spheroid generation, it is still elusive to fully reflect real stem cell niches; this effort majorly suffers from a lack of cell-extracellular matrix (ECM) interactions within the 3D spheroids. In this study, we develop a simple but versatile method for generating human MSC (hMSC) spheroids by culturing the cells on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). Interestingly, the pV4D4-coated surface allows a dynamic cell adhesion to the polymer surface while developing the formation of 3D spheroids. The corresponding mechanotransduction promotes the expression of the endogenous ECM and, in turn, results in a remarkable improvement in self-renewal abilities, pro-angiogenic potency, and multilineage differentiation capabilities. This observation highlights the significance of our method compared to the conventional spheroid-generating methods in terms of recreating the ECM-rich microenvironment. We believe the developed surface can serve as a versatile but reliable method for stem cell-based tissue engineering and regenerative medicine.

Antibacterial Nanopillar Array for an Implantable Intraocular Lens.

Postsurgical intraocular lens (IOL) infection caused by pathogenic bacteria can result in blindness and often requires a secondary operation to replace the contaminated lens. The incorporation of an antibacterial property onto the IOL surface can prevent bacterial infection and postoperative endophthalmitis. This study describes a polymeric nanopillar array (NPA) integrated onto an IOL, which captures and eradicates the bacteria by rupturing the bacterial membrane. This is accomplished by changing the behavior of the elastic nanopillars using bending, restoration, and antibacterial surface modification. The combination of the polymer coating and NPA dimensions can decrease the adhesivity of corneal endothelial cells and posterior capsule opacification without causing cytotoxicity. An ionic antibacterial polymer layer is introduced onto an NPA using an initiated chemical vapor deposition process. This improves bacterial membrane rupture efficiency by increasing the interactions between the bacteria and nanopillars and damages the bacterial membrane using quaternary ammonium compounds. The newly developed ionic polymer-coated NPA exceeds 99% antibacterial efficiency against Staphylococcus aureus, which is achieved through topological and physicochemical surface modification. Thus, this paper provides a novel, efficient strategy to prevent postoperative complications related to bacteria contamination of IOL after cataract surgery.

Remodeling of Adhesion Network within Cancer Spheroids via Cell-Polymer Interaction.

3D spheroids are considered as the improved in vitro model to mimic the distinct arrangements of the cells in vivo. To date, low-attachment surfaces have been most widely used to induce the spontaneous aggregation of cells in suspension by simply tuning the relative strength of the cell-cell adhesion over cell-substrate adhesion. However, aggregating cancer cells into 3D clusters should mean more than just adjoining the cells in the physical proximity. The tumor cell functionality is strongly affected by the adhesion networks between cancer cells and extracellular matrix (ECM). Here, we performed an in-depth analysis of how the nonmetastatic breast cancer cells (MCF7) can be transformed to gain invasive phenotypes through compact aggregation into 3D spheroids on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). By comparing the adhesion networks and invasion dynamics between 3D spheroids cultured on the pV4D4 surface with those cultured on conventional ultra-low-attachment (ULA) dishes, we report that only spheroids on the pV4D4 display active and sporadic cell-surface binding activities via dynamic protrusions, which correlates strongly with an increase in integrin ß1. Moreover, localized laminin expression at the core of the pV4D4-cultured spheroids confirms the prominence of the intimate integrin-laminin interactions prompted by the exposure to pV4D4. This study suggests that structurally and functionally dissimilar 3D spheroids can be generated from the same type of cells on the surfaces of different physicochemical properties without any chemical treatment or genetic manipulation.

A Surface-Tailoring Method for Rapid Non-Thermosensitive Cell-Sheet Engineering via Functional Polymer Coatings.

Cell sheet engineering, a technique utilizing a monolayer cell sheet, has recently emerged as a promising technology for scaffold-free tissue engineering. In contrast to conventional tissue-engineering approaches, the cell sheet technology allows cell harvest as a continuous cell sheet with intact extracellular matrix proteins and cell-cell junction, which facilitates cell transplantation without any other artificial biomaterials. A facile, non-thermoresponsive method is demonstrated for a rapid but highly reliable platform for cell-sheet engineering. The developed method exploits the precise modulation of cell-substrate interactions by controlling the surface energy of the substrate via a series of functional polymer coatings to enable prompt cell sheet harvesting within 100 s. The engineered surface can trigger an intrinsic cellular response upon the depletion of divalent cations, leading to spontaneous cell sheet detachment under physiological conditions (pH 7.4 and 37 °C) in a non-thermoresponsive manner. Additionally, the therapeutic potential of the cell sheet is successfully demonstrated by the transplantation of multilayered cell sheets into mouse models of diabetic wounds and ischemia. These findings highlight the ability of the developed surface for non-thermoresponsive cell sheet engineering to serve as a robust platform for regenerative medicine and provide significant breakthroughs in cell sheet technology.

A conformal nano-adhesive via initiated chemical vapor deposition for microfluidic devices.

A novel high-strength nano-adhesive is demonstrated for fabricating nano- and microfluidic devices. While the traditional plasma sealing methods are specific for sealing glass to poly(dimethylsiloxane) (PDMS), the new method is compatible with a wide variety of polymeric and inorganic materials, including flexible substrates. Additionally, the traditional method requires that sealing occur within minutes after the plasma treatment. In contrast, the individual parts treated with the nano-adhesive could be aged for at least three months prior to joining with no measurable deterioration of post-cure adhesive strength. The nano-adhesive is comprised of a complementary pair of polymeric nanolayers. An epoxy-containing polymer, poly(glycidyl methacrylate) (PGMA) was grown via initiated chemical vapor deposition (iCVD) on the substrate containing the channels. A plasma polymerized polyallylamine (PAAm) layer was grown on the opposing flat surface. Both CVD monomers are commercially available. The PGMA nano-adhesive layer displayed conformal coverage over the channels and was firmly tethered to the substrate. Contacting the complementary PGMA and PAAm surfaces, followed by curing at 70 degrees C, resulted in nano- and micro-channel structures. The formation of the covalent tethers between the complementary surfaces produces no gaseous by-products which would need to outgas. The nano-adhesive layers did not flow significantly as a result of curing, allowing the cross-sectional profile of the channel to be maintained. This enabled fabrication of channels with widths as small as 200 nm. Seals able to withstand > 50 psia were fabricated employing many types of substrates, including silicon wafer, glass, quartz, PDMS, polystyrene petri dishes, poly(ethylene terephthalate) (PET), polycarbonate (PC), and poly(tetrafluoro ethylene) (PTFE).

Prevention of Bacterial Colonization on Catheters by a One-Step Coating Process Involving an Antibiofouling Polymer in Water.

As reports of multidrug resistant pathogens have increased, patients with implanted medical catheters increasingly need alternative solutions to antibiotic treatments. As most catheter-related infections are directly associated with biofilm formation on the catheter surface, which, once formed, is difficult to eliminate, a promising approach to biofilm prevention involves inhibiting the initial adhesion of bacteria to the surface. In this study, we report an amphiphilic, antifouling polymer, poly(DMA-mPEGMA-AA) that can facilely coat the surfaces of commercially available catheter materials in water and prevent bacterial adhesion to and subsequent colonization of the surface, giving rise to an antibiofilm surface. The antifouling coating layer was formed simply by dipping a model substrate (polystyrene, PET, PDMS, or silicon-based urinary catheter) in water containing poly(DMA-mPEGMA-AA), followed by characterization by X-ray photoelectron spectroscopy (XPS). The antibacterial adhesion properties of the polymer-coated surface were assessed for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) growth under static (incubation in the presence of a bacterial suspension) and dynamic (bacteria suspended in a solution under flow) conditions. Regardless of the conditions, the polymer-coated surface displayed significantly reduced attachment of the bacteria (antiadhesion effect > ∼8-fold) compared to the bare noncoated substrates. Treatment of the implanted catheters with S. aureus in vivo further confirmed that the polymer-coated silicon urinary catheters could significantly reduce bacterial adhesion and biofilm formation in a bacterial infection animal model. Furthermore, the polymer-coated catheters did not induce hemolysis and were resistant to the adhesion of blood-circulating cells, indicative of high biocompatibility. Collectively, the present amphiphilic antifouling polymer is potentially useful as a coating platform that renders existing medical devices resistant to biofilm formation.

Hydrogel Functionalized Janus Membrane for Skin Regeneration.

In this study, a hydrogel functionalized Janus membrane is developed and its capacity is examined as a wound dressing biomaterial. A hydrophobic fluoropolymer, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl methacrylate) (PHFDMA), is uniformly coated onto macroporous polyester membrane through initiated chemical vapor deposition process on both sides. PHFDMA-coated macroporous membrane exhibits antibacterial property, allows air permeation, and inhibits water penetration. Janus membrane property is obtained by exposing one side of PHFDMA coated membrane with 1 m KOH solution, which allows PHFDMA cleavage resulting in carboxylic acid residue. This carboxylic acid residue is then further functionalized with gelatin methacrylate-based photocrosslinkable hydrogel for moisture retention and growth factor release. When applied to full thickness dorsal skin defect model, functionalized hydrogel allows moisture retention and hydrophobic surface prevents exudate leaks via water repellence. Furthermore, hydrogel functionalized Janus membrane enhances the wound healing rate and induces thick epidermal layer formation. In conclusion, the multifunctional Janus membrane with hydrophobic outer surface and immobilized hydrogel on the other surface is fabricated for an innovative strategy for wound healing.

Surface-Modified Mesh Filter for Direct Nucleic Acid Extraction and its Application to Gene Expression Analysis.

Rapid and convenient isolation of nucleic acids (NAs) from cell lysate plays a key role for onsite gene expression analysis. Here, this study achieves one-step and efficient capture of NA directly from cell lysate by developing a cationic surface-modified mesh filter (SMF). By depositing cationic polymer via vapor-phase deposition process, strong charge interaction is introduced on the surface of the SMF to capture the negatively charged NAs. The NA capturing capability of SMF is confirmed by X-ray photoelectron spectroscopy, fluorescent microscopy, and zeta potential measurement. In addition, the genomic DNAs of Escherichia Coli O157:H7 can be extracted by the SMF from artificially infected food, and fluorescent signal is observed on the surface of SMF after amplification of target gene. The proposed SMF is able to provide a more simplified, convenient, and fast extraction method and can be applied to the fields of food safety testing, clinical diagnosis, or environmental pollutant monitoring.

A Simple, Cost-Efficient Method to Separate Microalgal Lipids from Wet Biomass Using Surface Energy-Modified Membranes.

For the efficient separation of lipid extracted from microalgae cells, a novel membrane was devised by introducing a functional polymer coating onto a membrane surface by means of an initiated chemical vapor deposition (iCVD) process. To this end, a steel-use-stainless (SUS) membrane was modified in a way that its surface energy was systemically modified. The surface modification by conformal coating of functional polymer film allowed for selective separation of oil-water mixture, by harnessing the tuned interfacial energy between each liquid phase and the membrane surface. The surface-modified membrane, when used with chloroform-based solvent, exhibited superb permeate flux, breakthrough pressure, and also separation yield: it allowed separation of 95.5 ± 1.2% of converted lipid (FAME) in the chloroform phase from the water/MeOH phase with microalgal debris. This result clearly supported that the membrane-based lipid separation is indeed facilitated by way of membrane being functionalized, enabling us to simplify the whole downstream process of microalgae-derived biodiesel production.

Electroconductive Nanopatterned Substrates for Enhanced Myogenic Differentiation and Maturation.

Electrically conductive materials provide a suitable platform for the in vitro study of excitable cells, such as skeletal muscle cells, due to their inherent conductivity and electroactivity. Here it is demonstrated that bioinspired electroconductive nanopatterned substrates enhance myogenic differentiation and maturation. The topographical cues from the highly aligned collagen bundles that form the extracellular matrix of skeletal muscle tissue are mimicked using nanopatterns created with capillary force lithography. Electron beam deposition is then utilized to conformally coat nanopatterned substrates with a thin layer of either gold or titanium to create electroconductive substrates with well-defined, large-area nanotopographical features. C2C12 cells, a myoblast cell line, are cultured for 7 d on substrates and the effects of topography and electrical conductivity on cellular morphology and myogenic differentiation are assessed. It is found that biomimetic nanotopography enhances the formation of aligned myotubes and the addition of an electroconductive coating promotes myogenic differentiation and maturation, as indicated by the upregulation of myogenic regulatory factors Myf5, MyoD, and myogenin (MyoG). These results suggest the suitability of electroconductive nanopatterned substrates as a biomimetic platform for the in vitro engineering of skeletal muscle tissue.

Polymer Thin Films with Tunable Acetylcholine-like Functionality Enable Long-Term Culture of Primary Hippocampal Neurons.

In vitro culture systems for primary neurons have served as useful tools for neuroscience research. However, conventional in vitro culture methods are still plagued by challenging problems with respect to applications to neurodegenerative disease models or neuron-based biosensors and neural chips, which commonly require long-term culture of neural cells. These impediments highlight the necessity of developing a platform capable of sustaining neural activity over months. Here, we designed a series of polymeric bilayers composed of poly(glycidyl methacrylate) (pGMA) and poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA), designated pGMA:pDMAEMA, using initiated chemical vapor deposition (iCVD). Harnessing the surface-growing characteristics of iCVD polymer films, we were able to precisely engraft acetylcholine-like functionalities (tertiary amine and quaternary ammonium) onto cell culture plates. Notably, pGD3, a pGMA:pDMAEMA preparation with the highest surface composition of quaternary ammonium, fostered the most rapid outgrowth of neural cells. Clear contrasts in neural growth and survival between pGD3 and poly-l-lysine (PLL)-coated surfaces became apparent after 30 days in vitro (DIV). Moreover, brain-derived neurotrophic factor level continuously accumulated in pGD3-cultured neurons, reaching a 3-fold increase at 50 DIV. Electrophysiological measurements at 30 DIV revealed that the pGD3 surface not only promoted healthy maturation of hippocampal neurons but also enhanced the function of hippocampal ionotropic glutamate receptors in response to synaptic glutamate release. Neurons cultured long-term on pGD3 also maintained their characteristic depolarization-induced Ca2+ influx functions. Furthermore, primary hippocampal neurons cultured on pGD3 showed long-term survival in a stable state up to 90 days-far longer than neurons on conventional PLL-coated surfaces. Taken together, our findings indicate that a polymer thin film with optimal acetylcholine-like functionality enables a long-term culture and survival of primary neurons.

Application of monodirectional Janus patch to oromucosal delivery system.

Drug delivery through mucosae has received huge research attention owing to its advantageous characteristics such as accurate dose control and the avoidance of premature metabolism of vulnerable drugs by oral administration. However, body fluid in mucosae may dissolve the drug, releasing it to unwanted directions. Here, a Janus drug delivery patch with monodirectional diffusion property is devised to deliver drugs efficiently and to overcome the issue of unwanted drug release. A polyester fabric is coated with a hydrophobic polymer, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-heptadecafluorodecyl methacrylate), via initiated chemical vapor deposition. Subsequently, hydrophilicity is rendered selectively on one surface by base-catalyzed hydrolysis to obtain a Janus substrate with both hydrophobic and hydrophilic surfaces. The hydrophilic surface of the Janus substrate is further coated with resveratrol-loaded hydrogel to produce a Janus drug delivery patch. The fabricated patch efficiently blocks fluid penetration from one side to the other in mucous environment. Delivery of resveratrol through hairless mouse skin and reconstructed human mucosae using Janus patch shows higher permeation flux compared to bare control patch. The Janus drug delivery patch shown in this study can be a useful tool for efficient transmucosal delivery of various kinds of drugs.

Effects of interfacial layer wettability and thickness on the coating morphology and sirolimus release for drug-eluting stent.

Drug-eluting stents (DESs) have been used to treat coronary artery diseases by placing in the arteries. However, current DESs still suffer from polymer coating defects such as delamination and peeling-off that follows stent deployment. Such coating defects could increase the roughness of DES and might act as a source of late or very late thrombosis and might increase the incident of restenosis. In this regard, we modified the cobalt-chromium (Co-Cr) alloy surface with hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) or hydrophobic poly(2-hydroxyethyl methacrylate)-grafted-poly(caprolactone) (PHEMA-g-PCL) brushes. The resulting surfaces were biocompatible and biodegradable, which could act as anchoring layer for the drug-in-polymer matrix coating. The two modifications were characterized by ATR-FTIR, XPS, water contact angle measurements, SEM and AFM. On the control and modified Co-Cr samples, a sirolimus (SRL)-containing poly(D,L-lactide) (PDLLA) were ultrasonically spray-coated, and the drug release was examined for 8weeks under physiological conditions. The results demonstrated that PHEMA as a primer coating improved the coating stability and degradation morphology, and drug release profile for short-term as compared to control Co-Cr, but fails after 7weeks in physiological buffer. On the other hand, the hydrophobic PHEMA-g-PCL brushes not only enhanced the stability and degradation morphology of the PDLLA coating layer, but also sustained SRL release for long-term. At 8-week of release test, the surface morphologies and release profiles of coated PDLLA layers verified the beneficial effect of hydrophobic PCL brushes as well as their thickness on coating stability. Our study concludes that 200nm thickness of PHEMA-g-PCL as interfacial layer affects the stability and degradation morphology of the biodegradable coating intensively to be applied for various biodegradable-based DESs.