How To Track Blood Flow In Tiny Vessels

Scientists have designed gold nanoparticles, no bigger than 100 nanometres, which can be coated and used to track blood flow in the smallest blood vessels in the body. By improving our understanding of blood flow in vivo the nanoprobes represent an opportunity to help in the early diagnosis of diseaseLight microscopy is a rapidly evolving field for understanding in vivo systems where high resolution is required. It is particularly crucial for cardiovascular research, where clinical studies are based on ultrasound technologies which inherently have lower resolution and provide limited information.

The ability to monitor blood flow in the sophisticated vascular tree (notably in the smallest elements of the microvasculaturecapillaries) can provide invaluable information to understand disease processes such as thrombosis and vascular inflammation. There are further applications for the improved delivery of therapeutics, such as targeting tumours.

Currently, blood flow in the microvasculature is poorly understood. Nanoscience is uniquely placed to help understand the processes happening in the micron-dimensioned vessels. Designing probes to monitor blood flow is challenging because of the environment; the high protein levels in plasma and the high red blood cell concentrations are detrimental to optical imaging. Conventional techniques rely on staining red blood cells, using organic dyes with short-lived usage due to photobleaching, as the tracking motif. The relatively large size of the red blood cells (7-8 micrometres), which are effectively the probes, limits the resolution in imaging and analysis of flow dynamics of the smallest vessels which are of a similar width. Therefore, to have more detailed resolution and information about the blood flow in the microvasculature, even smaller probes are required.

The key to these iridium-coated nanoparticles lies in both their small size, and in the characteristic luminescent properties. The iridium gives a luminescent signal in the visible spectrum, providing an optical window which can be detected in blood. It is also long-lived compared to organic fluorophores, while the tiny gold particles are shown to be ideal for tracking flow and detect clearly in tissues“, explains Professor Zoe Pikramenou, from the School of Chemistry at  the University of Birmingham.

The findings have been published in the journal Nanomedicine.


Bionic Cardiac Patch

Scientists have built a “bioniccardiac patch that could act similarly to a pacemaker and monitor as well as respond to cardiac problems, a kind of nanocomputer. The researchers from Harvard University constructed nanoscale electronic scaffolds that can be seeded with cardiac cells to produce a bionic cardiac patch — the engineered heart tissue with ability to replace heart muscle damaged during a heart attack.

bionic cardiac patch

I think one of the biggest impacts would ultimately be in the area that involves replaced of damaged cardiac tissue with pre-formed tissue patches,” said Charles Lieber, who along with colleagues described the work in the journal Nature Nanotechnology. “Rather than simply implanting an engineered patch built on a passive scaffold, our works suggests it will be possible to surgically implant an innervated patch that would now be able to monitor and subtly adjust its performance,” he added.

Once implanted, the “bionic” patch could act similarly to a pacemakerdelivering electrical shocks to correct arrhythmia. Unlike traditional pacemakers, the “bionic” patch — because its electronic components are integrated throughout the tissue — can detect arrhythmia far sooner, and operate at far lower voltages. “Even before a person started to go into large-scale arrhythmia that frequently causes irreversible damage or other heart problems, this could detect the early-stage instabilities and intervene sooner,” Lieber said. “It can also continuously monitor the feedback from the tissue and actively respond,” he added.

The patch might also find use as a tool to monitor the responses under cardiac drugs, or to help pharmaceutical companies to screen the effectiveness of drugs under development.


How To Follow Nanoparticles In The Body

Treating a disease without causing side effects is one of the big promises of nanoparticle technology. But fulfilling it remains a challenge. One of the obstacles is that researchers have a hard time seeing where nanoparticles go once they’re inside various parts of the body. But now one team has developed a way to help overcome this problem — by making tissues and organs clearer in the lab. Their study on mice appears in the journal ACS Nano.

3D mapping of nanoparticle

Scientists are trying to design nanoparticles that deliver a therapeutic cargo directly to a disease site. This specific targeting could help avoid the nasty side effects that patients feel when a drug goes to heathy areas in the body. But barriers, such as blood vessel walls, can divert particles from reaching their intended destination. To get around such obstacles, scientists need a better understanding of how nanoparticles interact with structures inside the body. Current techniques, however, are limited. Warren C. W. Chan and colleagues from the University of Toronto  (Canada) wanted to develop a method to better track where nanoparticles go within tissues.

The researchers injected an acrylamide hydrogel into organs and tissues removed from mice. The gel linked all of the molecules together, except for the lipids, which are responsible for making tissues appear opaque. The lipids easily washed away, leaving the tissues clear but otherwise intact. Using this technique, the researchers could image nanoparticles at a depth of more than 1 millimeter, which is 25 times deeper than existing methods. In addition to helping scientists understand how nanoparticles interact with tumors and organs, the new approach could also contribute to tissue engineering, implant and biosensor applications, say the researchers.


Obesity: How To Burn Fat

Researchers at MIT and Brigham and Women’s Hospital have developed nanoparticles that can deliver antiobesity drugs directly to fat tissue. Overweight mice treated with these nanoparticles lost 10 percent of their body weight over 25 days, without showing any negative side effects. The drugs work by transforming white adipose tissue, which is made of fat-storing cells, into brown adipose tissue, which burns fat. The drugs also stimulate the growth of new blood vessels in fat tissue, which positively reinforces the nanoparticle targeting and aids in the white-to-brown transformation. These drugs, which are not FDA-approved to treat obesity, are not new, but the research team developed a new way to deliver them so that they accumulate in fatty tissues, helping to avoid unwanted side effects in other parts of the body.


The advantage here is now you have a way of targeting it to a particular area and not giving the body systemic effects. You can get the positive effects that you’d want in terms of antiobesity but not the negative ones that sometimes occur,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.

More than one-third of Americans are considered to be obese, and last year obesity overtook smoking as the top preventable cause of cancer death in the United States, with 20 percent of the 600,000 cancer deaths attributed to obesity.

Langer and Omid Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital, are the senior authors of the study, which appears in theProceedings of the National Academy of Sciences the week of May 2. The paper’s lead authors are former MIT postdoc Yuan Xue and former BWH postdoc Xiaoyang Xu.


Nanoparticle-Based Cancer Therapies Shown to Work in Humans

A team of researchers led by Caltech scientists has shown that nanoparticles can function to target tumors while avoiding adjacent healthy tissue in human cancer patients.

nanoparticle against brain cancer

Our work shows that this specificity, as previously demonstrated in preclinical animal studies, can in fact occur in humans“, says study leader Mark E. Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech. “The ability to target tumors is one of the primary reasons for using nanoparticles as therapeutics to treat solid tumors.
The scientists demonstrate that nanoparticle-based therapies can act as a “precision medicine” for targeting tumors while leaving healthy tissue intact. In the study, Davis and his colleagues examined gastric tumors from nine human patients both before and after infusion with a drug—camptothecin—that was chemically bound to nanoparticles about 30 nanometers in size.

Our nanoparticles are so small that if one were to increase the size to that of a soccer ball, the increase in size would be on the same order as going from a soccer ball to the planet Earth,” says Davis, who is also a member of the City of Hope Comprehensive Cancer Center in Duarte, California, where the clinical trial was conducted.

The team found that 24 to 48 hours after the nanoparticles were administered, they had localized in the tumor tissues and released their drug cargo, and the drug had had the intended biological effects of inhibiting two proteins that are involved in the progression of the cancer. Equally important, both the nanoparticles and the drug were absent from healthy tissue adjacent to the tumors.

The findings, have been published online in the journal Proceedings of the National Academy of Sciences.


Walking Again After Spinal Cord Injuries

Scientists at the Ecole Polytechnique Fédérale de Lausanne (EPFL)  in Switzerland proved in 2012 that electrical-chemical stimulation of the spinal cord could restore lower body movement in paralysed rats. Now they’re a step closer to making this a possibility for humans with spinal injuries. By applying so-called ‘surface implants‘ directly to the spinal cord, any movement or stretching of the nerve tissues could cause inflammation and, ultimately, rejection of the implant. This is their solution. Called e-Dura, it’s a soft and stretchy implant that can be bent and deformed similar to the living tissue that surrounds it.


One important aspect of our studies is that we design the implant so that it could, one day, be used in a therapeutical context. So we wanted an implant that could stay for quite some time in vivo without inducing any detrimental effect. And so the first question we asked was: is soft making a difference?“, said Professor Stephanie Lacour, co-author of the study at EPFL.
E-Dura has a small tube through which neuro-transmitting drugs can be administered to the injured tissue to reanimate nerve cells. Built by on-site engineers, the device is made from silicon substrate covered with stretchable gold electric conducting tracks. Researchers found that when the prototype was implanted into rats’ spinal cords it caused neither damage nor rejection, even after two months. They concede, however, there is one significant hurdle to overcome.

There’s no link at the moment between the brain; so the motor command between the brain and the actual stimulation pattern on the spinal cord. So we now also have to find a way to link the two so that the person will think about moving and, indeed, the stimulation will be synchronised“, comments Prof. Lacour.
The team has set its sights on human clinical trails, and sees potential new therapies for e-Dura to treat conditions such as epilepsy, Parkinson’s disease and pain management.


Nanotechnology To Heal Pets

Modern medicine is evolving quickly. Now, with the introduction of bioengineering, doctors can have tissue made for their patients and veterinarians are having great success using nanotechnology in our pets.
Dr. Jed Johnson has a PhD in engineering and his firm engineers body tissue. He explains: “The part that I focus on is tissue engineering, where we are basically focusing and building or engineering new tissue for the body.”
Their nanotechnology is an integral part of regenerative medicine.
We’ve all seen regeneration. We’ve all had cuts on our hands, right? And those cuts heal. So, our body is capable of healing, but we have to provide the right environment,” , said the Dr. Hutchinson, from Animal General in Cranberry.
Enter nanofibers.
It takes a hundred of the microscopic fibers laid side-by-side to be as wide as a human hair.
Weave them together, and they provide a framework for healing.
Cells and tissue can’t move across open space, they have to crawl on something, and this is really the key aspect to having a scaffold is it allows those cells to have a highway to move on to refill that wound, regenerate that native tissue,” Dr. Johnson said.
You can’t do that synthetically. I mean, we can’t do that without the help of what someone like Dr. Johnson’s doing with nanofibers,” Dr. Mike Hutchinson said.
Dr. Hutchinson uses nanofibers in combination with stem cells to speed up the healing.
They will do a lot of good for as long as they stay, but we would like to keep them there longer in that damaged environment. So, they have made some nanowhiskers, if you will, that we mix with the stem cells before we inject them in, and they will hold them there. They will give them something to grow on or to hug to and keep them there longer,” Dr. Hutchinson said.


Hybrid Patch Instead Of A Heart Transplant

Because heart cells cannot multiply and cardiac muscles contain few stem cells, heart tissue is unable to repair itself after a heart attack. Now Tel Aviv University (TAU) researchers are literally setting a new gold standard in cardiac tissue engineering.

Dr. Tal Dvir and his graduate student Michal Shevach of TAU‘s Department of Biotechnology, Department of Materials Science, and Center for Nanoscience , have been developing sophisticated micro- and nanotechnological tools — ranging in size from one millionth to one billionth of a meter — to develop functional substitutes for damaged heart tissues. Searching for innovative methods to restore heart function, especially cardiac “patches” that could be transplanted into the body to replace damaged heart tissue, Dr. Dvir literally struck gold. He and his team discovered that gold particles are able to increase the conductivity of biomaterials. In a study published by Nano Letters, Dr. Dvir’s team presented their model for a superior hybrid cardiac patch, which incorporates biomaterial harvested from patients and gold nanoparticles.

Our goal was twofold,” said Dr. Dvir. “To engineer tissue that would not trigger an immune response in the patient, and to fabricate a functional patch not beset by signalling or conductivity problems.”
We now have to prove that these autologous hybrid cardiac patches improve heart function after heart attacks with minimal immune response,” said Dr. Dvir. “Then we plan to move it to large animals and after that, to clinical trials.

How To Close Deep Wounds In A Few Seconds

A significant breakthrough could revolutionize surgical practice and regenerative medicine. A team led by Ludwik Leibler from the Laboratoire Matière Molle et Chimie (CNRS/ESPCI Paris Tech) and Didier Letourneur from the Laboratoire Recherche Vasculaire Translationnelle (INSERM/Université Paris Diderot and Université Paris 13) – France -, has just demonstrated that the principle of adhesion by aqueous solutions of nanoparticles can be used in vivo to repair soft-tissue organs and tissues.

This easy-to-use gluing method has been tested on rats. When applied to skin, it closes deep wounds in a few seconds and provides aesthetic, high quality healing. It has also been shown to successfully repair organs that are difficult to suture, such as the liver. Finally, this solution has made it possible to attach a medical device to a beating heart, demonstrating the method’s potential for delivering drugs and strengthening tissues.
This work has been published on the website of the journal Angewandte Chemie.

Bionic Ear

Scientists at Princeton University used off-the-shelf printing tools to create a functional ear that can “hear” radio frequencies far beyond the range of normal human capability. The researchers’ primary purpose was to explore an efficient and versatile means to merge electronics with tissue. The scientists used 3D printing of cells and nanoparticles followed by cell culture to combine a small coil antenna with cartilage, creating what they term a bionic ear.

bionic ear

In general, there are mechanical and thermal challenges with interfacing electronic materials with biological materials,” said Michael McAlpine, an assistant professor of mechanical and aerospace engineering at Princeton and the lead researcher. “Previously, researchers have suggested some strategies to tailor the electronics so that this merger is less awkward. That typically happens between a 2D sheet of electronics and a surface of the tissue. However, our work suggests a new approach — to build and grow the biology up with the electronics synergistically and in a 3D interwoven format.”


Cyborg Era Is Coming

Harvard scientists have created a type of “cyborg” tissue for the first time by embedding a three-dimensional network of functional, biocompatible, nanoscale wires into engineered human tissues.As described in a paper published Aug. 26 in the journal Nature Materials, a research team led by Charles M. Lieber, the Mark Hyman Jr. Professor of Chemistry at Harvard, and Daniel Kohane, a Harvard Medical School professor in the Department of Anesthesia at Children’s Hospital Boston, developed a system for creating nanoscale “scaffolds” that can be seeded with cells that grow into tissue.
The current methods we have for monitoring or interacting with living systems are limited,” said Lieber. “We can use electrodes to measure activity in cells or tissue, but that damages them. With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it. Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin.”

Charles M. Lieber explains: “With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it. Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin.”