Implantable microdevice for the treatment of hydrocephalus

We present a novel microdevice for the treatment of hydrocephalus. Hydrocephalus is a pathological condition in which excessive cerebrospinal fluid (CSF) is accumulated within the subarachnoid space of the brain due to deficient arachnoid granulations, resulting in the brain damage or death. Current treatment for hydrocephalus is to surgically implant a shunt device to drain the excessive fluid from the ventricles to peritoneal cavity or other parts of the body. This method has over 50% failure rate due to occlusions and mechanical failures of shunt components. The proposed microfabricated device can mimic the function of normalarachnoid granulations and thus can replace the deficient arachnoid granulations. The microfabricated arachnoid granulations (MAG) consist of arrays of microvalves and microneedles.The microvalves are made of a PDMS/Parylene composite layer and have a 3-D dome petal shape. Such geometry enables the microvalve to rectify fluid flow in the forward and backward direction due to pressure differentials like normal arachnoid granulation. Microvalve design was optimized using 3-D numerical simulation. The microvalves were fabricated using three main microfabrication techniques: diffuser lithography for dome-shaped SU-8 mold fabrication, thin polymer film deposition and reflow for PDMS/Parylene membrane formation, and excimer laser machining for valve opening. The pressure drop vs. flow rate characteristics of the fabricated microvalve was investigated through in-vitro flow tests using a bench-top CSF simulator. The results showed that a 10x10 microvalve array with combined opening shape is optimal for our application.The microneedle array is to surgically pierce the dura mater membrane after being assembled with the microvalve. The microneedles were fabricated using three main techniques: diffraction photolithography for tapered SU-8 needle fabrication, RIE etching for needle sharpening, and excimer laser machining for through-hole creation. Puncture tests were conducted using pig’s dura mater and the microneedles coated with a Ti layer showed promising results (16 out of 100 needles pierced dura and the needles were not deformed). Blood adhesion tests were also carried out using human blood simulating the CSF dynamics and no significant platelet adhesion was observed at the microneedles. The MAG presented in this dissertation demonstrates a great potential for the treatment of hydrocephalus.Ph.D., Mechanical Engineering and Mechanics -- Drexel University, 201

Microscale Strategies for Generating Cell-Encapsulating Hydrogels

Hydrogels in which cells are encapsulated are of great potential interest for tissue engineering applications. These gels provide a structure inside which cells can spread and proliferate. Such structures benefit from controlled microarchitectures that can affect the behavior of the enclosed cells. Microfabrication-based techniques are emerging as powerful approaches to generate such cell-encapsulating hydrogel structures. In this paper we introduce common hydrogels and their crosslinking methods and review the latest microscale approaches for generation of cell containing gel particles. We specifically focus on microfluidics-based methods and on techniques such as micromolding and electrospinning.National Science Foundation (U.S.) (DMR0847287)National Institutes of Health (U.S.) (EB008392)National Institutes of Health (U.S.) (DE019024)National Institutes of Health (U.S.) (HL099073)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL092836)United States. Army Research Office (contract W911NF-07-D-0004)United States. Army Research Office (Institute for Soldier Nanotechnology)United States. Army. Corps of EngineersInnovative Med Tech (Postdoctoral fellowship

Polypoidal Choroidal Vasculopathy in Korean Patients with Large Submacular Hemorrhage

PURPOSE: To determine and compare the clinical characteristics, visual prognosis and treatment of hemorrhagic polypoidal choroidal vasculopathy (HPCV) with those of hemorrhagic choroidal neovascularization (HCNV) due to age-related macular degeneration (ARMD). MATERIALS AND METHODS: Retrospective analysis of 44 consecutive eyes with a submacular hemorrhage comprising more than 50% of the neovascular lesion. Patients were diagnosed as having HPCV or HCNV on the basis of indocyanine green angiography. RESULTS: Of the 44 eyes with submacular hemorrhage, 26 were classified as HPCV and 18 as HCNV. The baseline patient characteristics were similar for both groups. At the final follow-up the HPCV group had 17 eyes showing visual improvement, four showing maintained vision, and five showing visual deterioration. In contrast, the HCNV group had four eyes showing visual improvement, one showing maintained vision, and 13 showing visual deterioration. Visual acuity of 0.05). CONCLUSION: PCV accounts for the largest proportion of submacular hemorrhage in Koreans. PCV showed a better visual prognosis than CNV.ope

Microbiome of Saliva and Plaque in Children According to Age and Dental Caries Experience

Dental caries are one of the chronic diseases caused by organic acids made from oral microbes. However, there was a lack of knowledge about the oral microbiome of Korean children. The aim of this study was to analyze the metagenome data of the oral microbiome obtained from Korean children and to discover bacteria highly related to dental caries with machine learning models. Saliva and plaque samples from 120 Korean children aged below 12 years were collected. Bacterial composition was identified using Illumina HiSeq sequencing based on the V3-V4 hypervariable region of the 16S rRNA gene. Ten major genera accounted for approximately 70% of the samples on average, including Streptococcus, Neisseria, Corynebacterium, and Fusobacterium. Differential abundant analyses revealed that Scardovia wiggsiae and Leptotrichia wadei were enriched in the caries samples, while Neisseria oralis was abundant in the non-caries samples of children aged below 6 years. The caries and non-caries samples of children aged 6-12 years were enriched in Streptococcus mutans and Corynebacterium durum, respectively. The machine learning models based on these differentially enriched taxa showed accuracies of up to 83%. These results confirmed significant alterations in the oral microbiome according to dental caries and age, and these differences can be used as diagnostic biomarkers

Microfluidic Generation of Core-Shell Microgels as a Versatile Cell-Culture Platform

Microfabrication technology provides a versatile platform for engineering hydrogels used in biomedical applications with high-resolution control and injectability. Herein, we present a strategy of fabricating core-shell microgel structures for applications as in vitro cell culture platform and injectable tissue constructs, by combining (1) microfluidics-assisted fabrication of microgels, and (2) providing silica hydrogel layer on the microgel surface. A flow-focusing microfluidic device was utilized to generate droplets containing photocrosslinkable methacrylated gelatin, followed by exposure to UB fabricate gelatin microgels. The size of the microgels could be easily controlled by varying the ratio of flow rates of aqueous and oil phases in the microfluidic device. The microgels were used as in vitro cell culture platform to grow cardiac cells on the microgel surface: The cells readily adhered on the microgel surface and proliferated over time while maintaining high viability (>90%). The cells on the microgels were also able to migrate to their surrounding area. In addition, the microgels eventually degraded over time. These results demonstrate that cell-seeded microgels have a great potential as injectable tissue constructs. Furthermore, we demonstrated that coating the cells on microgels with biocompatible, biodegradable silica hydrogels via sol–gel method provided significant protection against oxidative stress which is often encountered during injection into host tissues and detrimental to the cells. Overall, the microfluidic approach to generate cell-adhesive microgel core, coupled with silica hydrogels as a protective shell, will be highly useful as a cell culture platform to generate a wide range of injectable tissue constructs

Long-Term Increases and Recent Slowdowns of CO2 Emissions in Korea

Korea is one of the fastest-growing CO2-emitting countries but has recently experienced a dramatic slowdown in emissions. The objective of the study is to examine the driving factors of long-term increases (1990–2015) and their slowdown (2012–2015) in emissions of Korea. This study uses an extended index decomposition analysis model that better fits Korea’s emission trends of the last 25 years by encompassing 19 energy end-use sectors (18 economic sectors and a household sector) and three energy types. The results show that emission increases in the long term (1990–2015) come from economic growth and population growth. However, improvements in energy intensity, carbon intensity, and economic structure offset large portions of CO2 emissions. The recent slowdown (2012–2015) mainly resulted from a decline in energy intensity and carbon intensity in the economic sectors. Among the different energy types, electricity has played a significant role in decreasing emissions because industries have reduced the consumption of electricity per output and the source of electricity generation has shifted to cleaner energies. These results imply that the Korean government should support strategies that reduce energy intensity and carbon intensity in the future to reduce CO2 emissions and maintain sustainable development

Enhancing the Biocompatibility of Microfluidics-Assisted Microgel Fabrication with Channel Geometry

Microfluidic flow-focusing devices (FFD) are widely used to generate monodisperse droplets and microgels with controllable size, shape and composition for various biomedical applications. However, highly inconsistent and often low viability of cells encapsulated within the microgels prepared via microfluidic FFD has been a major concern, and yet this aspect has not been systematically explored. In this study, we demonstrate that the biocompatibility of microfluidic FFD to fabricate cell-laden microgels can be significantly enhanced by controlling the channel geometry. When a single emulsion (???single???) microfluidic FFD is used to fabricate cell-laden microgels, there is a significant decrease and batch-to-batch variability in the cell viability, regardless of their size and composition. It is determined that during droplet generation, some of the cells are exposed to the oil phase which had a cytotoxic effect..Therefore, a microfluidic device with a sequential (???double???) flow-focusing channels is employed instead, in which a secondary aqueous phase containing cells enters the primary aqueous phase, so the exposure of cells to the oil phase are minimized by directing them to the center of droplets. This microfluidic channel geometry significantly enhances the biocompatibility of cell-laden microgels, while maintaining the benefits of a typical microfluidic process.This study therefore provides a simple and yet highly effective strategy to improve the biocompatibility of microfluidic fabrication of cell-laden microgels