Bioinspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair

Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ≈30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures.United States. National Institutes of Health (GM086433)United States. National Institutes of Health (DE013023

Engineering arterial substitutes that recapitulate vessel microstructure and mimic native physiological responses

Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, September, 2020Cataloged from the official PDF version of thesis.Includes bibliographical references (pages 107-118).Engineering small caliber (< 6mm) arterial grafts remains an unsolved problem. Current synthetic and autologous grafts suffer from short and long-term limitations including decreased patency rates, risk of bacterial infection, and compliance mismatching that results in neointimal hyperplasia. Tissue engineering is seen as a solution; however, a true arterial replacement remains elusive. Despite the numerous publications that have appeared over the last three decades, most reported strategies mimic functional and structural arterial properties to a limited extent. Furthermore, these strategies require long maturation times before implantation and carry the risk of failure in patients, who are often elderly with multiple comorbidities. Our central hypothesis was that living arterial substitutes that display normal physiological responses after in vivo implantation can be engineered through the controlled assembly of vascular cells and free-standing collagen sheets of controlled fibril orientation in a manner that recapitulates native vessel microstructure. We first present a scalable and continuous strategy for generating strong, free-standing, ultrathin, and centimeter-wide collagen sheets with controlled anisotropy using a flow-focusing approach. This strategy represents the first of its kind to generate anisotropic collagen sheets with control over nano- and macro-molecular properties. Next, controlled assembly of vascular cells and free-standing collagen sheets allowed us to design living blood vessels that recapitulated the arterial wall microstructure, and through structural, mechanical and biological characterization confirmed mimicry of native physiologic properties. We believe that the scalable fabrication schemes, and thorough characterization techniques, presented here will serve as a strong reference for future blood vessel tissue engineering efforts.by David Miranda-Nieves.Ph. D.Ph.D. Harvard-MIT Program in Health Sciences and Technolog

Maniobrability analysis with FSRU / LNG prototype ships in a virtual stage of “El Cayao” maritime terminal and surroundings of Cartagena Bay

The research project was developed in association with the HÖEGH LNG company, to obtain a solution that would allow the standardization of its procedures, providing safe operations on the entrance and departure of FSRU / LNG ships to the maritime terminal “El Cayao”, within the Bay of Cartagena; the terminal was in the construction stage, so the maneuvers to be executed with this type of craft would be made for the first time in the country. The development of this research allowed the modeling of the virtual scenario, which incorporated relevant information from the area to be studied, the analysis of the behavior of ship prototypes integrated to the full mission bridge simulator and the training directed to national and international master pilots in the simulation of maneuvers, contributing significantly to the integral maritime security, for the entrance of the type FSRU / LNG (Floating Storage and Regasification Unit for Liquefied Natural Gas) ship, HÖEGH Grace, which made its entrance to the Bay of Cartagena on November 1, 2016, reaching the required standards to offer a safe, reliable and successful maneuver. This is how ENAP, through CIDIAM, contributes to the strengthening of maritime power in Colombia

Microfluidic platform for short-term chemotaxis assay.

<p>(<b>A</b>) Time-lapse images of MSCs migration under a PDGF-BB gradient for 24 hours. Images were taken every 15 minutes and individual color-coded cell tracks were assembled after 0, 8, 16, and 24 hours. A movie clip of the 24-hour cell migration data is available (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044995#pone.0044995.s008" target="_blank">Mov. S1</a>). (<b>B, C</b>) Migration traces of cells initially seeded in the lower PDGF-BB concentration region (cell no. 1-13) and in the higher PDGF-BB concentration region (cell no. 14-26), respectively. These cell traces (<b>B</b>) indicate that cells in the bottom half of the channel (0–50 ng/mL of PDGF-BB) exhibited directed migration, whereas (<b>C</b>) cells in the top half of the channel (50–100 ng/mL of PDGF-BB) exhibited random motion. Axes are in the units of 200 microns. (<b>D</b>) Chemotactic index, CI of MSCs in 0–50 ng/ml and 50–100 ng/ml PDGF-BB regions. Statistical significance was determined by Student's <i>t</i>-test comparing cells in the bottom and top parts of the channel (*p<0.05).</p

Microfluidic platform for long-term chemotaxis assay.

<p>(<b>A</b>) Long-term migration of MSCs (labeled with CFSE/Calcein AM) within a PDGF-BB gradient (0–100 ng/ml). The total number of cells present within the cell migration region was 105 at 0 hour and 107 at 72 hours. Limited by the visualization area of microscope, fluorescent images of adjacent areas were taken individually and spliced together. (<b>B</b>) Cell distribution within the cell migration region in the presence (0–100 ng/mL PDGF-BB) or absence (0-0 ng/mL or 100-100 ng/mL PDGF-BB) of a chemotactic gradient. Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044995#pone-0044995-g004" target="_blank">Figure 4A</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044995#pone.0044995.s003" target="_blank">S3</a>, and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044995#pone.0044995.s005" target="_blank">S5</a> were represented as ratios of number of cells present in the upper half of the channel to that in the lower half of the channel. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044995#s2" target="_blank">Results</a> are means ± STD for n = 3. Statistical significance was determined by Student's <i>t</i>-test comparing results in the presence of a gradient from 0 and 72 hours (*p<0.05).</p

Gradient evolution inside the microfluidic gradient generator.

<p>(<b>A</b>) A macroscopic image of the gradient generator. (<b>B–C</b>) Gradient evolution inside the microfluidic gradient generator at different pumping rates powered by mechanical pump: (<b>B</b>) Visualization of the gradient at level 2 (Lv2), 5 (Lv5), 8 (Lv8), and 10 (Lv10)), as denoted by the dashed boxes. Fluorescence images were captured within each zone 2 hours after starting the pump. Fluorescence intensity was measured in the middle of the cell migration region denoted by the red dashed lines. Yellow dashed lines denote the upper and lower boundaries of the microchannel. (<b>C</b>) Normalized fluorescence intensity of the fluorescein gradients along the cell migration channel (red dashed line in b) at different pumping rates. (<b>D</b>) Fluorescein gradient evolution across the cell migration region (Lv10) inside the microfluidic gradient generator powered by ALZET® osmotic pumps (5 µL/hr) throughout a 9-day period. Normalized by taking the fluorescent intensity at 0 µm as 1. (<b>E</b>) Shear stress within the cell migration region modeled using COMSOL. Inset at bottom: a model cell (height 1.5 µm), experiences shear stresses in the range of 0.03–0.14 dynes/cm².</p

Multicentre study of magnet ingestion in Spanish paediatric emergency departments.

INTRODUCTION: The ingestion of magnetic objects can cause complications in children, and there are no epidemiological or clinical data on the subject in Spain. OBJECTIVES: To determine the incidence, epidemiological characteristics and management of magnet ingestion in paediatric emergency departments in Spain. MATERIAL AND METHODS: Prospective observational multicentre study conducted over a 3-year period. The study universe consisted of patients aged less than 14 years. RESULTS: The incidence was 4.8 cases per 100 000 emergency care episodes. Of the 72 patients included (mean age, 7.2 years), 54% were male. Seven percent had neuropsychiatric disorders. Sixty-one percent of the magnets were spherical and 69% came from toys. The size was variable, most frequently between 5 and 10 mm (50%), and ranging from 3 to 30 mm. Eighty-six percent of patients were asymptomatic. The most frequent symptom was abdominal pain. Eighty-three percent of the patients sought medical care within 6 h of ingestion and 92% within 24 h. Thirty-one percent of the cases were of multiple ingestion. Endoscopy was required for extraction in 15% of cases, a proportion that rose to 36% in the group of cases of multiple ingestion. None of the patients required surgery. We did not observe any gastrointestinal complications of magnet ingestion. CONCLUSIONS: The ingestion of multiple magnets is less frequent than single magnet ingestion, and we did not observe any complications despite the lower frequency of procedures compared to other studies.The study was funded through the 2016 annual grant of the Research Network of the Sociedad Española de Urgencias de Pediatría (RiSEUP-SPERG), for an amount of euro 4000

Tracking Mesenchymal Stem Cells with Iron Oxide Nanoparticle Loaded Poly(lactide-co-glycolide) Microparticles

Monitoring the location, distribution and long-term engraftment of administered cells is critical for demonstrating the success of a cell therapy. Among available imaging-based cell tracking tools, magnetic resonance imaging (MRI) is advantageous due to its noninvasiveness, deep penetration, and high spatial resolution. While tracking cells in preclinical models via internalized MRI contrast agents (iron oxide nanoparticles, IO-NPs) is a widely used method, IO-NPs suffer from low iron content per particle, low uptake in nonphagocytotic cell types (e.g., mesenchymal stem cells, MSCs), weak negative contrast, and decreased MRI signal due to cell proliferation and cellular exocytosis. Herein, we demonstrate that internalization of IO-NP (10 nm) loaded biodegradable poly­(lactide-co-glycolide) microparticles (IO/PLGA-MPs, 0.4–3 μm) in MSCs enhances MR parameters such as the <i>r</i>₂ relaxivity (5-fold), residence time inside the cells (3-fold) and <i>R</i>₂ signal (2-fold) compared to IO-NPs alone. Intriguingly, in vitro and in vivo experiments demonstrate that internalization of IO/PLGA-MPs in MSCs does not compromise inherent cell properties such as viability, proliferation, migration and their ability to home to sites of inflammation