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Targeting Atherosclerotic Plaques with Stents made of Drug-eluting Biomaterials

Posted in Biodegradable Drug-eluting Material, Bioresorbable Vascular Scaffold (BVS), Cardiac and Cardiovascular Surgical Procedures, Frontiers in Cardiology and Cardiovascular Disorders, PCI, Peripheral Arterial Disease & Peripheral Vascular Surgery, Stents & Tools, Vascular Diseases on June 9, 2020| Leave a Comment »

Targeting Atherosclerotic Plaques with Stents made of Drug-eluting Biomaterials

Reporter: Daniel Menzin, BSc BioMedical Engineering, expected, May 2021, Research Assistant 4, Core Applications Developer and Acting CTO

Atherosclerosis is a chronic cardiovascular disease with a multitude of different implications. A coronary artery plaque may lead to congestive heart failure while an aortic plaque may cause angina. Both can quite possibly lead to a heart attack unless properly managed. One way to manage this condition is through the use of stents made of a mesh that is expanded following placement into the diseased vessel.

Unfortunately, stents are oftentimes initially effective but eventually restenosis occurs. Restenosis is a condition in which the affected vessel becomes blocked again. Cholesterol-rich blood vessel environments oftentimes lead to an irritation that results in white blood cells aggregating in the area and releasing proinflammatory chemokines and cytokines, which cause fibrosis. To make matters worse, the cholesterol plaques undergo compression against the vessel wall which causes vessel injury and further inflammation. This leads to thrombus formation and may potentiate neointimal hyperplasia, an abnormal proliferation and migration of smooth muscle cells in the tunica intima. Neointimal hyperplasia plays a major role in restenosis.

Recent research has found that interfacing drug eluting biomaterials with stents may help prevent restenosis. One study showed that rapamycin delivered with acid labile and ROS-sensitive forms of Beta-cyclodextrin produced promising results when treating atherosclerosis in rat models (Dou, et al). In this promising new paradigm of treatment, non-proinflammatory biomaterials are interfaced with stents. Once inflammation appears the biomaterial will begin to degrade, slowly releasing the drug which suppresses the underlying immune reaction and the resulting inflammation.

SOURCE

Dou Y;Chen Y;Zhang X;Xu X;Chen Y;Guo J;Zhang D;Wang R;Li X;Zhang J; “Non-Proinflammatory and Responsive Nanoplatforms for Targeted Treatment of Atherosclerosis.” Biomaterials, U.S. National Library of Medicine, 29 July 2017, pubmed.ncbi.nlm.nih.gov/28778000/.

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Drug Eluting Stents: On MIT‘s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES

Author: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/25/contributions-to-vascular-biology/

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Healing traumatic brain injuries with self-assembling peptide hydrogels

Posted in Biodegradable Drug-eluting Material, Brain Basis of Emotion, Materials Science & Engineering, Uncategorized, tagged blood brain barrier, neurons, peptide hydrogel, traumatic brain injury on September 27, 2019| Leave a Comment »

Healing traumatic brain injuries with self-assembling peptide hydrogels

Reporter : Irina Robu, PhD

In 2014, TBIs resulted in about 2.53 million emergency department visits in the U.S., according to the Centers for Disease Control and Prevention. A traumatic brain injury (TBI) can range from a mild concussion to a severe head injury. It is caused by a blow to the head or body, a wound that breaks through the skull or another injury that jars or shakes the brain. Individuals with traumatic brain injuries can develop secondary disorders after the initial blow. Researchers, Biplab Sarkar and Vivek Kumar from New Jersey Institute of Technology are hoping to prevent secondary disorders by injecting a self-assembling peptide hydrogel into the brains of rats with traumatic brain injury and see what happens. They observed that the hydrogel helped blood vessels regrow in addition to neuronal survival.

The researchers explained that after traumatic brain injury, the brain can amass glutamate which kills some neurons which is marked by overactive oxygen-containing molecules (oxidative stress), inflammation and disruption of the blood-brain barrier. Furthermore, TBI survivors can experience impaired motor control and depression. Within the experiment, the researchers showed that a week after injecting the gel in rats, the neurons have twice as many neurons at the injury site than the control animals did.

The NJIT researchers distinguished that they needed to inject the hydrogel directly in a rat’s brain just seconds after a TBI, which is not ideal, because it would be impossible to give a patient the treatment within that short period of time. The next step in showing that the self-assembling peptide hydrogel works is to combine their previous blood vessel-growing peptide and the new version to see whether it could enhance recovery. And the researchers plan to inspect whether the hydrogels work for more diffuse brain injuries such as concussions.

SOURCE

https://www.fiercebiotech.com/research/healing-traumatic-brain-injuries-self-assembling-peptide-hydrogels

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3-D Printing in Water with Novel Hybrid Nanoparticles

Posted in 3D Plotting Scaffolds, 3D Printing for Medical Application, Biodegradable Drug-eluting Material, Materials Science & Engineering, tagged 3D printing, Medical Applications, nanoparticles, Photoinitiator, Water Soluble Material on September 16, 2017| Leave a Comment »

3-D Printing in Water using Novel Hybrid Nanoparticles

Reporter: Irina Robu, PhD

3D printing has become an essential tool for fabricating different organic based materials, but printing structures in water has been thought-provoking due to lack of water soluble molecules known as photo initiators. The photo initiator can induce chemical reactions needed to form solid printed material by light. However, researchers at the Hebrew University of Jerusalem’s Center for Nanoscience and Nanotechnology have developed a new type of photo initiator for three-dimensional printing in water. This innovative nanoparticle allows the creating of bio-friendly 3D structures.

By 3D printing in water, it also opens up the digital light processing method to medical applications, leading toward a competitive response for patient specific implants and tissues because the photo initiators cause rapid solidification of a liquid material that can create faster reactions when exposed to light. 3D printing in water opens up innovative ways for tailored fabrication of medical devices and for printing hydrogels or bio-scaffolds that are typical used in tissue engineering.

The challenge of 3D printing in water is finding an initiator that is not consumed by irradiation. However, unlike regular photo initiators, the novel hybrid nanoparticles developed by Prof. Magdassi present tunable properties, wide excitation window in the UV and visible range, high light sensitivity, and their ability to split water, and absorb oxygen molecules that typically inhibit the performance of the process. The particles added as photo initiator are semi conductive hybrid nanoparticles and are used to create high resolution 3D objects at sub-microscopic scale.

Therefore, 3-D printing in water could allow personalized fabrication of joint replacements, heart valves, artificial tendons and ligaments etc.

SOURCE

https://phys-org.cdn.ampproject.org/c/s/phys.org/news/2017-08-rapid-d-hybrid-nanoparticles.amp
Amol Ashok Pawar et al. Rapid Three-Dimensional Printing in Water Using Semiconductor–Metal Hybrid Nanoparticles as Photoinitiators, Nano Letters (2017)

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Healing Side of Troublesome T Cells

Posted in Biodegradable Drug-eluting Material, Immunology, Immunotherapy, tagged biomaterials, blood cells, healing, helper T cells, immune cells, interlukin-4 on April 24, 2016| Leave a Comment »

Healing Side of Troublesome T Cells

Reported by: Irina Robu, PhD

Researchers from John Hopkins and Kennedy Krieger Institute report that immune system cells related to allergies similarly turn out to direct healing of mouse muscle wounds when paired with biologic “scaffolding” to support them. The paper published in Science on April 15,2016 show that immune system is the key to fighting infectious diseases but also kick-start healing after injury and indicate that biomaterial scaffolds can more effectively spur healing if designed to partner with immune cells.

According to research done by Jennifer Elisseeff, PhD from John Hopkins University School of Medicine, biodegradable scaffolds have shown promise in promoting regrowth of damage tissue by giving the body’s own stem cells a place to anchor and start their work. The same scaffolds also spark healing activity from immune cells.

To learn more about the immune cells involved and their response, the researchers in Elisseeff’s lab surgically removed part of the thigh muscles of mice and implanted scaffolds known to promote healing in animals. After a week, wound sites with scaffolds had more white blood cells than did wounds without scaffolds, and many of those cells were churning out a chemical signal, interleukin-4, type 2 helper T cells. To understand what the role of those cells might be, the team performed the same procedure on mice genetically modified to lack T cells and found that their wounds didn’t ramp up interleukin production or heal as well as those of the normal mice. Supplementary investigation revealed that one role of the type 2 helper T cells was to activate and train another type of immune cell, called macrophages, at the wound site. “

Elisseeff notes that there is still much to learn about how immune cells respond to various kinds of biomaterials that might be used as scaffolds — an area her team continues to investigate.

Source

http://medicalxpress.com/news/2016-04-troublesome-cells-side.html

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Dissolvable Sensor for Determining Temperature and Pressure

Posted in Bio Instrumentation in Experimental Life Sciences Research, Bio-MEMS, Biodegradable Drug-eluting Material, Medical Devices R&D and Inventions, Uncategorized, tagged dissolvable sensors on February 17, 2016| Leave a Comment »

Dissolvable sensor for determining temperature and pressure

Curator: Danut Dragoi, PhD

The Concept

The concept of dissolvable sensor in human body fluid and its experimentation was a successful task of electrical engineers at the University of Illinois at Urbana-Champaign. The device is intended to be implanted inside the head of human body in order to measure important parameters such as temperature and pressure.

Based on actual silicon technology, the device is built on a very thin silicon crystal, which is dissolvable in human body fluids after a given period and after the measurements are done. The need for such device is required by a medical intervention, a surgery, or a special medication.

For measuring the temperature,the device uses the principle of variation of current / voltage of a silicon diode with temperature see link in here . To illustrate how the diode works as a thermometer, see the link in here in which the curve voltage output versus temperature, variable T, is a decreasing linear function as a function of temperature.The other variable pressure P can be obtained from the base material, the thin silicon substrate, even if silicon is not a traditional piezoelectric material. Knowing that silicon can be a piezorezistive material, link in here, a signal output can be obtained from an engineered part of the silicon chip that has the resistance as a function of pressure P.

Two Variable Sensor: Temperature and Pressure

The picture bellow, IMAGE CREDIT::JOHN A. ROGERS, UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN AND MDTMAG.COM,

is the actual device made by electrical engineers at the University of Illinois at Urbana-Champaign. The device shown in the picture, SOA in the field, is based on silicon and is bioresorbable. The coil in the center is for transmission data purposes. The link in here describes in more details the device.

According with Prof Rogers of University of Illinois at Urbana-Champaign, a new class of small, thin electronic sensors can monitor temperature and pressure within the skull – which are crucial health parameters after a brain injury or surgery – then melt away when they are no longer needed, eliminating the need for additional surgery to remove the monitors and reducing the risk of infection and hemorrhage. Similar sensors can be adapted for postoperative monitoring in other body systems as well. John A. Rogers and Wilson Ray, a professor of neurological surgery at the Washington University School of Medicine in St. Louis, published their work in the journal Nature.

Applications of the device

After a traumatic brain injury or brain surgery, it is crucial to monitor the patient for swelling and pressure on the brain. Current monitoring technology is bulky and invasive,and the wires restrict the patient’s movement and hamper physical therapy as they recover.

Because they require continuous, hard-wired access into the head, such implants also carry the risk of allergic reactions, infection and hemorrhage, and even could exacerbate the inflammation they are meant to monitor. Professor Rogers mentioned that the demonstration was done on animal models, with a measurement precision that’s just as good as that of conventional devices.

The sensors, smaller than a grain of rice, are built on extremely thin sheets of silicon – which are naturally biodegradable – that are configured to function normally for a few weeks, then dissolve away, completely and harmlessly, in the body’s own fluids.

Rogers’ group teamed with Illinois materials science and engineering professor Paul V. Braun to make the silicon platforms sensitive to clinically relevant pressure levels in the intracranial fluid surrounding the brain. They also added a tiny temperature sensor and connected it to a wireless transmitter roughly the size of a postage stamp, implanted under the skin but on top of the skull.

The Illinois group worked with clinical experts in traumatic brain injury at Washington University to implant the sensors in rats, testing for performance and bio-compatibility. They found that the temperature and pressure readings from the dissolvable sensors matched conventional monitoring devices for accuracy.

The researchers are moving toward human trials for this technology, as well as extending its functionality for other bio-medical applications.

Source

Nature(2016), Published online 18 January 2016, Bioresorbable silicon electronic sensors for the brain, Seung-Kyun Kang, Rory K. J. Murphy, Suk-Won Hwang, Seung Min Lee, Daniel V. Harburg, Neil A. Krueger, Jiho Shin, Paul Gamble, Huanyu Cheng, Sooyoun Yu, Zhuangjian Liu, Jordan G. McCall, Manu Stephen, Hanze Ying, Jeonghyun Kim, Gayoung Park, R. Chad Webb, Chi Hwan Lee, Sangjin Chung, Dae Seung Wie, Amit D. Gujar, Bharat Vemulapalli, Albert H. Kim, Kyung-Mi Lee, Jianjun Cheng, Younggang Huang, Sang Hoon Lee, Paul V. Braun, Wilson Z. Ray & John A. Rogers,

http://www.nature.com/nature/journal/v530/n7588/fig_tab/nature16492_SF1.html

http://www.pveducation.org/pvcdrom/pn-junction/diode-equation

Click to access ME189_Chapter%207.pdf

https://news.illinois.edu/blog/view/6367/312684

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3D “Squeeze” Helps Adult Cells Become Stem Cells

Posted in 3D Printing for Medical Application, Biodegradable Drug-eluting Material, BioPrinting in Regenerative Medicine, Materials Science & Engineering, Stem Cells for Regenerative Medicine, Tissue Engineering, tagged 3D extracellular matrix, Cell Biology, microenviroment, pluripotency, Stem cell on January 14, 2016| Leave a Comment »

3D “Squeeze” Helps Adult Cells Become Stem Cells

Reporter: Irina Robu, PhD

Scientists based at Ecole Polytechnique Fédérale de Lausanne led by Matthias Lutolf have been engineering 3D extracellular matrices—gels. These scientists report that they have developed a gel that boosts the ability of normal cells to revert into stem cells by simply “squeezing” them.

The detail of the scientists’ work appeared in Nature Materials, January 11, 2015 in an article entitled, “Defined three-dimensional microenvironments boost induction of pluripotency.” According to the authors they find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodeling. They concluded that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.

The researchers discovered that they could reprogram the cells faster and more efficiently by simply adjusting the composition, hence the stiffness and density of the surrounding gel. As a result, the gel exerts different forces on the cells, “squeezing” them.

The scientists propose that the 3D environment is key to this process, generating mechanical signals that work together with genetic factors to make the cell easier to transform into a stem cell. The technique can be applied to a large number of cells to produce stem cells on an industrial scale.

Source

http://www.genengnews.com/gen-news-highlights/3d-squeeze-helps-adult-cells-become-stem-cells/81252223/

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Platform Technologies for Directly Reconstructing 3D Living Biomaterials

Posted in 3D Plotting Scaffolds, 3D Printing for Medical Application, Biodegradable Drug-eluting Material, Bioengineering & reverse engineering design, Materials Science & Engineering, Regenerative Biology and Medicine, Stem Cells for Regenerative Medicine, Tissue Engineering, Tissue Engineering and Regenerative Medicine, tagged 3D living scaffolds, artificial constructs, biopolymers, Cell bearing droplets, electrospinning, electrospraying, Extracellular matrix, scaffold on January 13, 2016| Leave a Comment »

Platform Technologies for Directly Reconstructing 3D Living Biomaterials

Reporter: Irina Robu, PhD

The techniques of electrospraying and electrospinning have existed for at least a century. These techniques employs a high voltage applied to a needle accommodating the flow of media, placed above a counter electrode which could either be grounded or have an opposite charge to the needle—thus introducing the charged media to an electric field.

These endeavors have demonstrated the wider applicability of these technologies and hence in the last 20 years or so have been used for the direct handling of a wide range of materials, including bio-inspired materials. These investigations have generated interest in areas such as the development of fine monolayered surfaces, fabrication of scaffolds which could be used for many laboratory-based fundamental biological studies.

In 2005, Jayasinghe et al. began investigations into both electrospraying and electrospinning of immortalized cell lines. Even though the high voltages involved, these cells were found to be viable post-electrospraying/electrospinning. Additional work has extended these studies to different cell types, both murine and human, immortalized or primary, stem cells, and even whole fertilized embryos from model organisms. Established protocols (such as flow cytometry, genetic/genomic interrogation, and microarray analysis) proved that cells processed using either electrospraying or electrospinning were indistinguishable from controls. Hence bio-electrospraying (BES) and cell electrospinning (CE) have become platform technologies for the biological and life science and are the leading technologies for the direct handling of cells—both for distribution of cells with pinpoint precision as cell-bearing droplets, and for the formation of truly 3D living scaffolds.

Previous studies have been carried out with processed cells suspended in matrices generated from animal/tumor-derived materials which contain largely uncharacterized growth factors and bioactive signals. This makes them very undesirable for clinical assays. While not applicable to humans, they can be used with advanced biopolymers, which could be directly translated to humans, and have the potential for creating artificial constructs which could be used for a variety of applications in the regenerative medicine field. The present study describes the in vivo application of such biopolymers, using murine macrophages to interrogate biocompatibility and cellular behavior post-transfer.

Source

http://onlinelibrary.wiley.com/doi/10.1002/adma.201503001/full