Biomimetic hydrogel-CNT network induced enhancement of fluid-structure interactions for ultrasensitive nanosensors

Flexible, self-powered, miniaturized, ultrasensitive flow sensors are in high demand for human motion detection, myoelectric prosthesis, biomedical robots, and health-monitoring devices. This paper reports a biomimetic nanoelectromechanical system (NEMS) flow sensor featuring a PVDF nanofiber sensing membrane with a hydrogel infused, vertically aligned carbon nanotube (VACNT) bundle that mechanically interacts with the flow. The hydrogel-VACNT structure mimics the cupula structure in biological flow sensors and gives the NEMS flow sensor ultrahigh sensitivity via a material-induced drag force enhancement mechanism. Through hydrodynamic experimental flow characterization, this work investigates the contributions of the mechanical and structural properties of the hydrogel in offering a sensing performance superior to that of conventional sensors. The ultrahigh sensitivity of the developed sensor enabled the detection of minute flows generated during human motion and micro-droplet propagation. The novel fabrication strategies and combination of materials used in the biomimetic NEMS sensor fabrication may guide the development of several wearable, flexible, and self-powered nanosensors in the future.Singapore. Prime Minister’s Offic

Cupula-Inspired Hyaluronic Acid-Based Hydrogel Encapsulation to Form Biomimetic MEMS Flow Sensors

Blind cavefishes are known to detect objects through hydrodynamic vision enabled by arrays of biological flow sensors called neuromasts. This work demonstrates the development of a MEMS artificial neuromast sensor that features a 3D polymer hair cell that extends into the ambient flow. The hair cell is monolithically fabricated at the center of a 2 µm thick silicon membrane that is photo-patterned with a full-bridge bias circuit. Ambient flow variations exert a drag force on the hair cell, which causes a displacement of the sensing membrane. This in turn leads to the resistance imbalance in the bridge circuit generating a voltage output. Inspired by the biological neuromast, a biomimetic synthetic hydrogel cupula is incorporated on the hair cell. The morphology, swelling behavior, porosity and mechanical properties of the hyaluronic acid hydrogel are characterized through rheology and nanoindentation techniques. The sensitivity enhancement in the sensor output due to the material and mechanical contributions of the micro-porous hydrogel cupula is investigated through experiments.Singapore. National Research Foundation (Campus for Research Excellence and Technological Enterprise programme

Studies on the release behavior of drugs in hyaluronic acid-nano/micro carrier composite hydrogels

Hyaluronic acid (HA) is a natural polymer that has gained significant attention as a potential biomaterial for a wide range of biomedical applications due to its unique physical and chemical properties. The mechanical and degradation properties of HA can be improved by physically or chemically crosslinking the chains into hydrogels. HA hydrogels have been extensively investigated as drug delivery carriers; however, the release of entrapped drugs is rapid and cannot be sustained significantly. Composite hydrogels of HA with drug loaded particulate carriers have been developed recently that combine advantages of physical/chemical properties of HA and sustained release property of entrapped drug carriers. These systems have not been studied in detail in terms of the transport behavior of drugs through the crosslinked networks. This transport is affected by several factors and understanding the mechanisms of drug transport would help to optimize the design of HA based composite hydrogels for specific therapeutic applications. In this work, HA based composite hydrogels were developed with drug loaded egg phosphatidylcholine (EPC) liposomes, poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), and PLGA microparticles (MPs) and investigated for in vitro drug release and physical stability of entrapped carriers. 5-Fluorouracil (5Fu) and latanoprost (Ltp) were selected as model hydrophilic and hydrophobic drug, respectively. HA was modified using methacrylic anhydride (MA) and adipic dihydrazide (ADH) moieties and then crosslinked to obtain hydrogels and characterized for morphology, swelling behavior, rheology, and in vitro drug release. 5Fu was loaded into PLGA MPs and Ltp was loaded into EPC liposomes, PLGA NPs, and PLGA MPs. The delivery carriers were characterized for morphology, size distribution, % encapsulation efficiency (EE), and in vitro drug release. From drug release studies, it was found that 5Fu was rapidly released from HA hydrogels alone but encapsulating it inside PLGA MPs prolonged the release up to several days. Ltp was found to release slowly from HA hydrogels alone but the release was sustained from PLGA MPs and EPC liposomes for several days and weeks, respectively. In case of composite hydrogels, the release of 5Fu and Ltp was significantly retarded as compared to MPs and liposomes alone. Retardation from composite hydrogels was dependent upon hydrogel network structure surrounding the entrapped particulate carriers in case of 5Fu release but not for Ltp release. Degradation studies showed that there was no difference in the degradation rate of drug loaded PLGA MPs with or without hydrogel, thus indicating that the retardation of drugs from composite hydrogels was due to the additional diffusion barrier of gel network surrounding the MPs and liposomes. Future work should involve further evaluation and optimization of various factors that affect drug transport in these HA based composite hydrogels to develop them into potential sustained release carriers for different types of drugs. Drug release from composite hydrogels in the presence of enzyme hyaluronidase would be useful to study for estimating the in vivo release behavior. In addition, quantitative estimation of diffusion coefficients and resistances would be important to understand the drug release kinetics of composite systems in detail and to develop a generalized model.DOCTOR OF PHILOSOPHY (MSE

Release retardation of model protein on polyelectrolyte-coated PLGA nano- and microparticles

PEM capsules have been proposed for vehicles of drug microencapsulation, with the release triggered by pH, salt, magnetic field, or light. When built on another carrier encapsulating drugs, such as nanoparticles, it could provide additional release barrier to the releasing drug, providing further control to drug release. Although liposomes have received considerable attention with PEM coating for sustained drug release, similar results employing PEM built on poly(lactic-co-lycolic acid) (PLGA) particles is scant. In this work, we demonstrate that the build-up pH and polyelectrolyte pairs of PEM affect the release retardation of BSA from PLGA particles. PAH/PSS pair, the most commonly used polyelectrolyte pair, was used in comparison with PLL/DES. In addition, we also demonstrate that the release retardation effect of PEM-coated PLGA particles diminishes as the particle size increases. We attribute this to the diminishing relative thickness of the PEM coating with respect to the size of the particle as the particle size increases, reducing the diffusional resistance of the PEM.Published versio

Flexible Hydrogel Capacitive Pressure Sensor for Underwater Applications

This paper reports development of a novel, flexible hydrogel based capacitive pressure sensor. It features a simple design of hydrogel thin film sandwiched between two gold electrodes. The sensor shows linear increase in output with increase in pressure. The microporous network of hydrogel enables high water retention while its flexible and stretchable structure ensures usage over large areas. These factors, combined with its stability in water, make it an ideal candidate for underwater applications. Further, the physical and chemical properties of hydrogels can be tailored to tune the capacitance to specific sensing needs. Flexible arrays of capacitive sensors with hydrogel hold great potential for underwater smart skin applications. Keywords: capacitive; hydrogel; pressure sensor; smart ski

Biomimetic hydrogel-CNT network induced enhancement of fluid-structure interactions for ultrasensitive nanosensors

Flexible, self-powered, miniaturized, ultrasensitive flow sensors are in high demand for human motion detection, myoelectric prosthesis, biomedical robots, and health-monitoring devices. This paper reports a biomimetic nanoelectromechanical system (NEMS) flow sensor featuring a PVDF nanofiber sensing membrane with a hydrogel infused, vertically aligned carbon nanotube (VACNT) bundle that mechanically interacts with the flow. The hydrogel-VACNT structure mimics the cupula structure in biological flow sensors and gives the NEMS flow sensor ultrahigh sensitivity via a material-induced drag force enhancement mechanism. Through hydrodynamic experimental flow characterization, this work investigates the contributions of the mechanical and structural properties of the hydrogel in offering a sensing performance superior to that of conventional sensors. The ultrahigh sensitivity of the developed sensor enabled the detection of minute flows generated during human motion and micro-droplet propagation. The novel fabrication strategies and combination of materials used in the biomimetic NEMS sensor fabrication may guide the development of several wearable, flexible, and self-powered nanosensors in the future.NRF (Natl Research Foundation, S’pore)Published versio

Release retardation from nanoparticles with odd and even number of layers.

<p>Release retardation from particles coated at unadjusted pH with PAH/PSS (A,B), with PLL/DES at pH 4 (C,D), and with PLL/DES at pH 9 (E,F). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092393#pone-0092393-g004" target="_blank">Figure 4</a> for the release from uncoated particles. Increasing the pH during PEM build-up increases the release retardation.</p

Effect of particle size on release retardation.

<p>The morphology of particles of size 160 μm (A), 60 μm (B), and 2 μm (C), is shown above their respective release profiles (D, E, F). The loading values, are, respectively, 2.2±0.2%, 5.0±0.1%, 2.6±0.1%. Release retardation is observed only at 2 μm.</p

Total BSA loss amount.

<p>NA: Not adjusted. Values are calculated based on drug content.</p