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Archive for the ‘Tissue Engineering’ Category


Functioning Human Neural Networks Grown in 3-D from Stem Cells

Reporter: Irina Robu, PhD

 

Researchers at Tuffs University developed three-dimensional human tissue model that mimics structural and functional features of the brain and were able to demonstrate sustained neural activity over several months. The 3D brain tissue models were the result of a collaborative effort between researchers from Tufts University School of Engineering, Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences at Tufts, and the Jackson Laboratory.

 

These tissue models have the ability to populate a 3D matrix of silk protein and collagen with cells from patients with Parkinson’s disease, Alzheimer’s disease and the ability to

  • explore cell interactions,
  • disease progression and
  • response to treatment.

The 3D brain tissue models overcome a crucial challenge of previous models which is the availability of human source neurons due to the fact that neurological tissues are rarely removed from

  • healthy patients, and are usually available
  • post-mortem from diseased patients.

The 3D tissue models are populated with human induced pluripotent stem cells (iPSCs) that can be derived from several sources, including patient skin. The iPSCs are generated by turning back the clock on cell development to their embryonic-like precursors. They can then be dialed forward again to any cell type, including neurons. The porous structure of the 3D tissue cultures labeled in the research delivers sufficient oxygenation, access for nutrients and measurement of cellular properties. A clear window in the center of each 3D matrix allows researchers to visualize the

  • growth,
  • organization and
  • behavior of individual cells.

According to David L. Kaplan, “the silk-collagen scaffolds provide the right environment to produce cells with the genetic signatures and electrical signaling found in native neuronal tissues”. Compared to growing and culturing cells in two dimensions, the three-dimensional matrix yields a knowingly extra complete mix of cells found in neural tissue, with the appropriate morphology and expression of receptors and neurotransmitters. Other researchers have used iPSCs to create brain-like organoids, but can still make it difficult figuring out what individual cells are doing in real time. Likewise, cells in the center of the organoids may not obtain enough oxygen or nutrients to function in a native state.

However, the researchers can see a great advantage of the 3D tissue models with advanced imaging techniques, and the addition of cell types such as microglia and endothelial cells,to create a more complete model of the brain environment and the complex interactions that are involved in

  • signaling,
  • learning and plasticity, and
  • degeneration.

 

SOURCE

https://www.rdmag.com/news/2018/10/scientists-grow-functioning-human-neural-networks-3d-stem-cells

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3D Print Shape-Shifting Smart Gel

Reporter: Irina Robu, PhD

Hydrogel scaffolds that mimic the native extracellular matrix (ECM) environment play a crucial role in tissue engineering and they are ubiquitously in our lives, including in contact lenses, diapers and the human body.

Researchers at Rutgers have invented a printing method for a smart gel that can be used to create materials for transporting small molecules like drugs to human organs. The approach includes printing a 3D object with a hydrogel that changes shape over time when temperature changes. The potential of the smart hydrogels could be to create a new are of soft robotics and enable new applications in flexible sensors and actuators, biomedical devices and platforms or scaffolds for cells to grow.

Rutgers engineers operated with a hydrogel that has been in use for decades in devices that generate motion and biomedical applications such as scaffolds for cells to grow on. The engineers learned how to precisely control hydrogel growth and shrinkage. In temperatures below 32 degrees Celsius, the hydrogel absorbs more water and swells in size. When temperatures exceed 32 degrees Celsius, the hydrogel begins to expel water and shrinks, the study showed.

According to the Rutgers engineers, the objects they can produce with the hydrogel range from the width of a human hair to several millimeters long. The engineers also showed that they can grow one area of a 3D-printed object by changing temperatures.

Source

https://news.rutgers.edu/rutgers-engineers-3d-print-shape-shifting-smart-gel/20180131

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A magnetic wire could replace the lottery of cancer blood tests

Reporter: Irina Robu, PhD

Stanford University scientists developed a magnetic wire which doctors can use to detect cancer before symptoms are detected in patients. The device is threaded into a vein, screens for the disease by attracting scarce and hard to capture tumor cells just like a magnet. The wire would be predominantly valuable to detect ‘silent killers’ such as pancreatic, ovarian and kidney cancer where symptoms only seem in the late stages when it has spread too far to treat. The magnetic wire can save thousands of lives by catching the disease at a time when drugs would be effective. Cells that have broken off a tumor to wander the bloodstream easily can assist as cancer biomarkers signaling the presence of the disease.

Dr. Gambhir’s team published the results in Nature Biomedical Engineering which described how using a wire that has magnetic nano-particles engineered to stick to cancerous cells. The original experiment is on pigs, which are structurally alike to humans and suffer from the same genetic malfunctions that cause cancer. The wire captured 10 to 80 times more tumor cells and was placed in a vein near the pig’s ear which can be removed from and the cells can be used for analysis. In real standings it chosen up 500 to 5,000 more cancerous cells than normal blood samples.

The circulating tumor cells were magnetized with nanoparticles containing an antibody that latch onto them. When attached, the cell carries the tiny magnet around with it and flows past the wire to veer from its regular path in the bloodstream and stick to the wire.  Professor Gambhir hopes that this approach will enrich detection capability and give insight how circulating tumor cells are and how early on they exist once the cancer is present. Once the technology is accepted for humans, the goal is to mature it into a multi-pronged tool that will increase detection, diagnosis, treatment and evaluation of cancer therapy.

It can also be used to gather genetic information about tumors located in places from where it’s hard to take biopsies.

Source

http://med.stanford.edu/news/all-news/2018/07/magnetized-wire-could-be-used-to-detect-cancer-in-people.html

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Print’s Technology Used to Help Produce 3D Printed Glass Molds for Droplet Microfluidic Chips

Reporter: Irina Robu, PhD

Scientists from Leibniz HKI, Friedrich Schiller University, the Ilmenau University of Technology, FEMTOprint  and the Fraunhofer Institute for Applied Optics and Precision Engineering fabricated 3D polydimethylsiloxane (PDMS) chips for droplet microfluidics by using FEMTOprint’s innovative glass technology to make 3D printed glass molds. The 3D printed glass mold can pack 192 nozzles into a design that’s 25 mm long and 4 mm wide, including all inlets and outlets, which produce monodisperse droplets of 70 µm. It’s also easy to scale this structure so it is capable of holding 1,000 nozzles in a 6.5 cm structure.

FEMTOprint’s direct writing process makes it possible to produce microfluidic designs with diverse levels, continuously changing heights, and complex 3D shapes, along with sub-micrometric resolution. 3D printed glass molds are used to combine the replication and ease of production that soft lithography is capable of with the advantages of high-resolution prototyping. Moreover, it can facilitate fabrication of multilevel structures even ones with gradients of confinement, which can make important droplet microfluidic operations better.

This technique, paired with simple polydimethylsiloxane replica molding, can offer users with a solution for non-specialized and specialized labs in order to customize and expand microfluidic experimentation. In order to leverage the immense potential of droplet microfluidics, the process of chip design and fabrication needs to be simplified. While the PDMS replica molding has significantly transformed the chip-production process, its dependence on 2D-limited photolithography has limited the design possibilities, as well as further dissemination of microfluidics to non-specialized labs. The technique permits new possibilities in the university, meanwhile as of right now, no other methodology exists except this one that allows architectures with structures from 15 µm to hundreds of micrometers in all dimensions to be produced.

According to FEMTOprint, 3D printed glass structures characterize a negative part, and can be used as chips by bonding them to a PDMS slab or glass, which makes it possible to utilize structures, like mirrors, lenses, and filters, that replica molding cannot recreate. Chip fabrication doesn’t have to be the holdup for non-microfluidic labs adopting microfluidic approaches, instead it should be looked at as a way to device novel functionalities, like optical fiber incorporation for fluorescence detection.

 SOURCE

https://www.industrial-lasers.com/articles/2018/07/3d-printing-creates-molds-for-droplet-microfluidic-chips.html

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New Liver Tissue Implants Showing Potential

Reporter: Irina Robu,PhD

To develop new tissues, researchers at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh have found that stem cells transformed into 3-D liver tissue can support liver function when implanted into the mice suffering with a liver disease.

The scientists stimulated human embryonic stem cells and induced pluripotent stem cells to mature pluripotent stem cells into liver cells, hepatocytes. Hepatocytes are the chief functional cells of the liver and perform an astonishing number of metabolic, endocrine and secretory functions. Hepatocytes are exceptionally active in synthesis of protein and lipids for export. The cells are grown in 3-D conditions as small spheres for over a year. However, keeping the stem cells as liver cells for a long time is very difficult, because the viability of hepatocytes decreases in-vitro conditions.

Succeeding the discovery, the team up with materials chemists and engineers to detect appropriate polymers that have already been approved for human use that can be developed into 3-D scaffolds. The best material to use a biodegradable polyester, called polycaprolactone (PCL).PCL is degraded by hydrolysis of its ester linkages in physiological conditions (such as in the human body) and it is especially interesting for the preparation of long term implantable devices, owing to its degradation which is even slower than that of polylactide. They spun the PCL into microscopic fibers that formed a scaffold one centimeter square and a few millimeters thick.

At the same time, hepatocytes derived from embryonic cells had been grown in culture for 20 days and were then loaded onto the scaffolds and implanted under the skin of mice.Blood vessels successfully grew on the scaffolds with the mice having human liver proteins in their blood, demonstrating that the tissue had successfully integrated with the circulatory system. The scaffolds were not rejected by the animals’ immune systems.

The scientists tested the liver tissue scaffolds in mice with tyrosinaemia,a potentially fatal genetic disorder where the enzymes in the liver that break down the amino acid tyrosine are defective, resulting in the accumulation of toxic metabolic products. The implanted liver tissue aided the mice with tyrosinaemia to break down tyrosine and the mice finally lost less weight, had less buildup of toxins in the blood and exhibited fewer signs of liver damage than the control group that received empty scaffolds.

According to Rob Buckle, PhD, Chief Science Officer at the MRC, “Showing that such stem cell-derived tissue is able to reproduce aspects of liver function in the lab also offers real potential to improve the testing of new drugs where more accurate models of human tissue are needed”. It is believed that the discovery could be the next step towards harnessing stem cell reprogramming technologies to provide renewable supplies of liver tissue products for transplantation.

SOURCE

https://www.rdmag.com/article/2018/08/new-liver-tissue-implants-showing-promise?et_cid=6438323

 

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Artificial Skin That “Feels” Temperature Changes

Reporter: Irina Robu, PhD

Engineers and scientists at California Institute of Technology (Caltech) and ETH Zurich developed an artificial skin capable of detecting temperature changes using a mechanism similar to the biological mechanism that allow snakes to sense prey through heat.  In those organs, ion channels in the cell membrane of sensory nerve fibers expand as temperature increases. This dilation allows calcium ions to flow, triggering electrical impulses.

The material used is a long chain molecule found in plant cells which gives the skin its temperature sensing capabilities. The team chose pectin because the pectin molecules in the film have a weakly bonded double-strand structure that contains calcium ions. As temperature increases, these bonds break down and the double strands “unzip,” releasing the positively charged calcium ions.

This would make pectin sensors useful for industrial applications, such as thermal sensors in consumer electronics or robotic skins to augment human-robot interactions. However, they need to change the fabrication process as that the current process leads to the presence of water which tends to bubble or evaporate at high temperatures.

Source

https://www.rdmag.com/news/2017/01/engineers-create-artificial-skin-feels-temperature-changes?cmpid=verticalcontent

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Intelligent Implant Biomaterials

Reporter: Irina Robu, PhD

Implants are gradually being used to treat various bone defects. A key factor for long term success of implants is the proper selection of the implant biomaterial. The biologic environment does not accept completely any material so to optimize biologic performance, implants should be selected to reduce the negative biologic response while maintaining adequate function. The implanted structure must if possible stimulate new bone formation, integrate with existing tissue and lastly be resorbed by the body to enable healthy bone growth.

The EU-funded MGNIM project which tailored biodegradable magnesium implant materials focused on producing aluminum- free Mg-based material suitable for bone applications. MAGNIM produced over 20 different Mg alloys and evaluated their mechanical and structural properties. In addition, they assessed their biological interaction, more specifically their corrosion-behavior. Out of these, two of the new alloys (Mg-2Ag and Mg-10Gd) were nominated for animal trials as pilot results indicated an anti-inflammatory function of degradation products.

The two new alloys, Mg-2Ag and Mg-10Gd as well as Mg alloy WE43 were tested in-vivo for biodegradability and functionality. Screws made of these materials were inserted into the femur of rats and their degradation was monitored. Imaging and histological data from explants revealed new bone formation in the screw implant site.

Even though the project has ended, additional testing in large animal models will be carried out prior to human clinical trials. MAGNIM partners propose to optimize implant material homogeneity and surface properties.

SOURCE
http://cordis.europa.eu/result/rcn/150629_en.html

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Novel Blood Substitute – ErythroMer

Reporter: Irina Robu, PhD

For years, scientists have tried ineffectively to create an artificial molecule that emulates the oxygen-carrying function of human red blood cell but the efforts failed because of oxygen delivery and safety issues. Now, a group of researchers led by Dr. Alan Doctor at Washington University in Saint Louis, are trying to resuscitate blood substitutes with a new nanotechnology-based, artificial red blood cell may overcome the problems that killed products designed by a team of companies such as BiopureAlliance PharmaceuticalsNorthfield Labs and even Baxter. Dr. Alan Doctor’s new company, Kalocyte is advancing the development of the

The donut-shaped artificial cells, ErythroMer are one-fiftieth the size of human red blood cells. ErythroMer is a novel blood substitute composed of a patented nanobialys nanoparticle. A special lining and control system tied to changes in blood Ph allows Erythromer to grab onto oxygen in the lungs and then dispense the oxygen in tissues where it is needed. The new artificial cells are intended to sidestep problems with vasoconstriction or narrowing of blood vessels.

Erythromer is stored freeze dried and reconstituted with water when needed but it can also be stored at room temperature which makes it for military and civilian trauma.

Trials have been successful in rats, mice, and rabbits, and human trials are planned. However, moving Erythromer into human clinical trials is still 8-10 years away.

SOURCE

https://www.thestreet.com/story/13913099/1/human-blood-substitutes-once-dead-now-resuscitated.html

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3-D Printed Ovaries Produce Healthy Offspring

Reporter: Irina Robu, PhD

Each year about 120,000 organs are transplanted from one human being to another and most of the time is a living volunteer. But lack of suitable donors, predominantly means the supply of such organs is inadequate. Countless people consequently die waiting for a transplant which has led researchers to study the question of how to build organs from scratch.

One promising approach is to print them, but “bioprinting” remains largely experimental. Nevertheless, bioprinted tissue is before now being sold for drug testing, and the first transplantable tissues are anticipated to be ready for use in a few years’ time. The first 3D printed organ includes bioprosthetic ovaries which are constructed of 3D printed scaffolds that have immature eggs and have been successful in boosting hormone production and restoring fertility was developed by Teresa K. Woodruff, a reproductive scientist and director of the Women’s Health Research Institute at Feinberg School of Medicine, at Northwestern University, in Illinois.

What sets apart these bioprosthetic ovaries is the architecture of the scaffold. The material is made of gelatin made from broken-down collagen that is safe to humans which is self-supporting and can lead to building multiple layers.

The 3-D printed “scaffold” or “skeleton” is implanted into a female and its pores can be used to optimize how follicles, or immature eggs, get wedged within the scaffold. The scaffold supports the survival of the mouse’s immature egg cells and the cells that produce hormones to boost production. The open construction permits room for the egg cells to mature and ovulate, blood vessels to form within the implant enabling the hormones to circulate and trigger lactation after giving birth. The purpose of this scaffold is to recapitulate how an ovary would function.
The scientists’ only objective for developing the bioprosthetic ovaries was to help reestablish fertility and hormone production in women who have suffered adult cancer treatments and now have bigger risks of infertility and hormone-based developmental issues.

 

SOURCES

Printed human body parts could soon be available for transplant
https://www.economist.com/news/science-and-technology/21715638-how-build-organs-scratch

 

3D printed ovaries produce healthy offspring giving hope to infertile women

http://www.telegraph.co.uk/science/2017/05/16/3d-printed-ovaries-produce-healthy-offspring-giving-hope-infertile/

 

Brave new world: 3D-printed ovaries produce healthy offspring

http://www.naturalnews.com/2017-05-27-brave-new-world-3-d-printed-ovaries-produce-healthy-offspring.html

 

3-D-printed scaffolds restore ovary function in infertile mice

http://www.medicalnewstoday.com/articles/317485.php

 

Our Grandkids May Be Born From 3D-Printed Ovaries

http://gizmodo.com/these-mice-gave-birth-using-3d-printed-ovaries-1795237820

 

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Fibrin-coated Electrospun Polylactide Nanofibers Potential Applications in Skin Tissue Engineering

Reported by: Irina Robu, PhD

 

Fibrin plays an essential role during wound healing and skin regeneration and is often applied for the treatment of skin injuries. Fibrin is formed after thrombin cleavage of fibrinopeptide A from fibrinogen Aalpha-chains, thus initiating fibrin polymerization. Double-stranded fibrils form through end-to-middle domain (D:E) associations, and concomitant lateral fibril associations and branching create a clot network. In addition, its primary role is to provide scaffolding for the intravascular thrombus.

Dr. Lucie Bacakova and her colleagues from Department of Biomaterials and Tissue engineering at Czech Academy of Sciences prepared electrospun nanofibrious membranes made from poly(L-lactide) modified with a thin fibrin nanocoating. The cell-free fibrin nanocating remained stable in cell culture medium for 14 days and did not change its morphology. The rate of fibrin degradation is correlated to the degree of cell proliferation on membrane populated with human dermal fibroblasts. It was shown that the cell spreading, mitochondrial activity and cell population density were higher on membranes coated with fibrin than on nonmodified membranes. The cell performance was improved by adding ascorbic acid in the cell culture medium. At the same time, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts. The expression of beta-integrins was improved by fibrin. And it is shown that the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acids is beneficial to tissue engineering.

Source

https://www.dovepress.com/articles.php?article_id=25743#

 

 

 

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