Tag Archives: B.

A nano fabrication technique used to create next generation heart valve

I am going to have take the researchers’ word that these somehow lead to healthy heart valve tissue,

In rotary jet spinning technology, a rotating nozzle extrudes a solution of extracellular matrix (ECM) into nanofibers that wrap themselves around heart valve-shaped mandrels. By using a series of mandrels with different sizes, the manufacturing process becomes fully scalable and is able to provide JetValves for all age groups and heart sizes. Credit: Wyss Institute at Harvard University

From a May 18, 2017 news item on ScienceDaily,

The human heart beats approximately 35 million times every year, effectively pumping blood into the circulation via four different heart valves. Unfortunately, in over four million people each year, these delicate tissues malfunction due to birth defects, age-related deteriorations, and infections, causing cardiac valve disease.

Today, clinicians use either artificial prostheses or fixed animal and cadaver-sourced tissues to replace defective valves. While these prostheses can restore the function of the heart for a while, they are associated with adverse comorbidity and wear down and need to be replaced during invasive and expensive surgeries. Moreover, in children, implanted heart valve prostheses need to be replaced even more often as they cannot grow with the child.

A team lead by Kevin Kit Parker, Ph.D. at Harvard University’s Wyss Institute for Biologically Inspired Engineering recently developed a nanofiber fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofiber network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM). To achieve this, the team used the Parker lab’s proprietary rotary jet spinning technology — in which a rotating nozzle extrudes an ECM solution into nanofibers that wrap themselves around heart valve-shaped mandrels. “Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes — much faster than possible for other regenerative prostheses,” said Parker.

A May 18,2017 Wyss Institute for Biologically Inspired Engineering news release (also on EurekAlert), which originated the news item, expands on the theme of Jetvalves,

To further develop and test the clinical potential of JetValves, Parker’s team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute. As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves. In Hoerstrup’s approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an “off-the-shelf” human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue. “In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal’s heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth. While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve’s much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimizing the number of pediatric re-operations,” said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth. The team is also working towards a GMP-grade version of their customizable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Hoerstrup is Chair and Director of the University of Zurich’s Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team’s goal is to provide customized, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.

“Achieving the goal of minimally invasive, low-cost regenerating heart valves could have tremendous impact on patients’ lives across age-, social- and geographical boundaries. Once again, our collaborative team structure that combines unique and leading expertise in bioengineering, regenerative medicine, surgical innovation and business development across the Wyss Institute and our partner institutions, makes it possible for us to advance technology development in ways not possible in a conventional academic laboratory,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

This scanning electron microscopy image shows how extracellular matrix (ECM) nanofibers generated with JetValve technology are arranged in parallel networks with physical properties comparable to those found in native heart tissue. Credit: Wyss Institute at Harvard University

Here’s a link to and a citation for the paper,

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement by Andrew K. Capulli, Maximillian Y. Emmert, Francesco S. Pasqualini, b, Debora Kehl, Etem Caliskan, Johan U. Lind, Sean P. Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Webe, Josue A. Goss. Biomaterials Volume 133, July 2017, Pages 229–241  https://doi.org/10.1016/j.biomaterials.2017.04.033

This paper is behind a paywall.

Researchers at Karolinska Institute (Sweden) build an artificial neuron

Unlike my post earlier today (June 26, 2015) about BrainChip, this is not about neuromorphic engineering (artificial brain), although I imagine this new research from the Karolinska Institute (Institutet) will be of some interest to that community. This research was done in the interest of developing* therapeutic interventions for brain diseases. One aspect of this news item/press release I find particularly interesting is the insistence that “no living parts” were used to create the artificial neuron,

A June 24, 2015 news item on ScienceDaily describes what the artificial neuron can do,

Scientists have managed to build a fully functional neuron by using organic bioelectronics. This artificial neuron contain [sic] no ‘living’ parts, but is capable of mimicking the function of a human nerve cell and communicate in the same way as our own neurons do. [emphasis mine]

A June 24, 2015 Karolinska Institute press release (also on EurekAlert), which originated the news item, describes how neurons communicate in the brain, standard techniques for stimulating neuronal cells, and the scientists’ work on a technique to improve stimulation,

Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell.

To date, the primary technique for neuronal stimulation in human cells is based on electrical stimulation. However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet in collaboration with collegues at Linköping University, have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells.

“Our artificial neuron is made of conductive polymers and it functions like a human neuron,” says lead investigator Agneta Richter-Dahlfors, professor of cellular microbiology. “The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored.”

The research team hope that their innovation, presented in the journal Biosensors & Bioelectronics, will improve treatments for neurologial disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function.

“Next, we would like to miniaturize this device to enable implantation into the human body,” says Agneta Richer-Dahlfors. “We foresee that in the future, by adding the concept of wireless communication, the biosensor could be placed in one part of the body, and trigger release of neurotransmitters at distant locations. Using such auto-regulated sensing and delivery, or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged.”

Here’s a link to and a citation for the paper,

An organic electronic biomimetic neuron enables auto-regulated neuromodulation by Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, b, Dagmar Galter, Magnus Berggren, and Agneta Richter-Dahlfors. Biosensors and Bioelectronics Volume 71, 15 September 2015, Pages 359–364         doi:10.1016/j.bios.2015.04.058

This paper is behind a paywall.

As to anyone (other than myself) who may be curious about exactly what they used (other than “living parts”) to create an artificial neuron, there’s the paper’s abstract,

Current therapies for neurological disorders are based on traditional medication and electric stimulation. Here, we present an organic electronic biomimetic neuron, with the capacity to precisely intervene with the underlying malfunctioning signalling pathway using endogenous substances. The fundamental function of neurons, defined as chemical-to-electrical-to-chemical signal transduction, is achieved by connecting enzyme-based amperometric biosensors and organic electronic ion pumps. Selective biosensors transduce chemical signals into an electric current, which regulates electrophoretic delivery of chemical substances without necessitating liquid flow. Biosensors detected neurotransmitters in physiologically relevant ranges of 5–80 µM, showing linear response above 20 µm with approx. 0.1 nA/µM slope. When exceeding defined threshold concentrations, biosensor output signals, connected via custom hardware/software, activated local or distant neurotransmitter delivery from the organic electronic ion pump. Changes of 20 µM glutamate or acetylcholine triggered diffusive delivery of acetylcholine, which activated cells via receptor-mediated signalling. This was observed in real-time by single-cell ratiometric Ca2+ imaging. The results demonstrate the potential of the organic electronic biomimetic neuron in therapies involving long-range neuronal signalling by mimicking the function of projection neurons. Alternatively, conversion of glutamate-induced descending neuromuscular signals into acetylcholine-mediated muscular activation signals may be obtained, applicable for bridging injured sites and active prosthetics.

While it’s true neither are “living parts,” I believe both enzymes and organic electronic ion pumps can be found in biological organisms. The insistence on ‘nonliving’ in the press release suggests that scientists in Europe, if nowhere else, are still quite concerned about any hint that they are working on genetically modified organisms (GMO). It’s ironic when you consider that people blithely use enzyme-based cleaning and beauty products but one can appreciate the* scientists’ caution.

* ‘develop’ changed to ‘developing’ and ‘the’ added on July 3, 2015.

SpiderSense and wearable computers

Nancy Owano in her Feb. 23, 2013 article for phys.org, Wearable display meets blindfold test for sensing danger, features a project (SpiderSense) from the University of Illinois at Chicago that will be presented at the Augmented Human ’13 conference to be held March 7 – 8, 2013 in Stuttgart, Germany,

The researchers behind SpiderSense define it as a wearable device that projects the wearer’s near environment on the skin. The suit gives the user a special directional awareness of surrounding objects. They have explored a scenario where multiple sites over the body, rather than just hands, are fitted with transducers. These transducers relay information about the wearer’s environment into tactile sensations.

Modules are distributed across the suit to give the wearer as near to 360-degree ultrasound coverage as possible. The system modules can scan the environment; they are controlled through a Controller Box. The box carries the power source, the electronics and the system logic. The modules and the Controller Box are connected by means of ten pin ribbon cables. The researchers said that, in the future, this could be replaced by a wireless Bluetooth connection.

You can find out more about SpiderSense from its presentation webpage on the University of Illinois at Chicago Electronic Visualization Laboratory (EVL) website,

Sensing the environment through SpiderSense     

authors: Mateevitsi,V., Haggadone, B., Leigh, J., Kunzer, B., Kenyon, R.V.

Augmented Human ’13, 4th International Conference in Cooperation with ACM SIGCHI, Stuttgart, Germany

Recent scientific advances allow the use of technology to expand the number of forms of energy that can be perceived by humans. Smart sensors can detect hazards that human sensors are unable to perceive, for example radiation. This fusing of technology to human’s forms of perception enables exciting new ways of perceiving the world around us. In this paper we describe the design of SpiderSense, a wearable device that projects the wearer’s near environment on the skin and allows for directional awareness of objects around him. The millions of sensory receptors that cover the skin presents opportunities for conveying alerts and messages. We discuss the challenges and considerations of designing similar wearable devices.

Victor Mateevisti wearing SpiderSense image provided by L. Long, EVL

Victor Mateevisti wearing SpiderSense
image provided by L. Long, EVL

A Feb. 22, 2013 article by Hal Hodson for New Scientist inspired Owano who acknowledges that to be the case in her end notes,

Mateevitsi [Victor Mateevitsi] tested the suit out on students, getting them to stand outside on campus, blindfolded, and “feel” for approaching attackers. Each wearer had ninja cardboard throwing stars to use whenever they sensed someone approaching them. “Ninety five per cent of the time they were able to sense someone approaching and throw the star at them,” says Mateevitsi.

The SpiderSense presentation is scheduled for March 7, 2013 at the Augmented Human ’13 conference or as it’s also known, the 4th International Conference in Cooperation with ACM SIGCHI (Association for Computing Machinery, Special Interest Group on Computer-Human Interaction). The team, as per Hal Hodson’s article,  hopes to start human trials of SpiderSense with visually impaired individuals.