Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have developed a nanoengineered bioink with improved bonding and cross-linking capabilities for 3D bioprinting of tumor models. A key component of this bioink is Laponite, highly charged, disk-shaped, crystalline nanoparticles. As explained in their recent paper in Biofabrication, these nanoparticles were shown to enhance the biological signaling that occurs in the tumor microenvironment so that more accurate tumor models can be created for study and anti-tumor drug development.
Tumor microenvironments are complex, with a supportive, connective tissue matrix containing multiple cellular components such as tumor cells, immune cells, organ specific cells, and collagen-producing cancer-associated fibroblasts. In addition, there is extensive cell-to-cell physical interaction and interactive signaling via a variety of biological factors that are difficult to model in an accurate and representative manner… Continue reading.
Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have developed a contact lens that can capture and detect exosomes, nanometer-sized vesicles found in bodily secretions which have the potential for being diagnostic cancer biomarkers. The lens was designed with microchambers bound to antibodies that can capture exosomes found in tears. This antibody- conjugated signaling microchamber contact lens (ABSM-CL) can be stained for detection with nanoparticle-tagged specific antibodies for selective visualization. This offers a potential platform for cancer pre-screening and a supportive diagnostic tool that is easy, rapid, sensitive, cost-effective, and non-invasive.
Exosomes are formed within most cells and secreted into many bodily fluids, such as plasma, saliva, urine, and tears. Once thought to be the dumping grounds for unwanted materials from their cells of origin, it is now known that exosomes can transport different biomolecules between cells. It has also been shown that there is a wealth of surface proteins on exosomes – some that are common to all exosomes and others that are increased in response to cancer, viral infections, or injury. In addition, exosomes derived from tumors can strongly influence tumor regulation, progression, and metastasis… Continue reading.
Published research on new eye treatment delivery shows improvement over hypodermic needles
A collaborative team, including scientists from the Terasaki Institute for Biomedical Innovation (TIBI), has developed a novel, self-plugging microneedle for injecting therapeutics into the eyes, potentially solving one of the major challenges of treating eye diseases – accurate delivery of therapeutic drugs to the retina, while guarding against possible complications at the injection site.
Recently published in the journal Advanced Healthcare Materials , the research shows preclinical evidence that this innovative, biodegradable microneedle, dip-coated with a therapeutic drug for release upon insertion into the eyeball, can also be equipped with a special hydrogel that simultaneously seals off the insertion hole. Additionally, this self-plugging microneedle can be fabricated with different needle lengths, so therapeutics can be precisely targeted and dispersed to retinal tissues or other areas within the eyeball… Continue reading.
Just mentioning a ruptured Achilles tendon would make anyone wince. Tendon injuries are well known for their lengthy, difficult and often incomplete healing processes. Sudden or repetitive motion, experienced by athletes and factory workers, for example, increases the risk of tears or ruptures in the tendons; thirty percent of all people will have a tendon injury, with the risk being highest in women. What’s more, those who suffer from these injuries are more prone to further injuries at the site or never recover fully.
Tendons are bands of fibrous connective tissue that attach muscles to bones. They are soft tissues connected to stiff bones; this creates a complex interface with a very specific structure. Following injury, this structure is disrupted, and the connective tissue changes from a linear to a kinked formation. Excess scarring can also occur, changing the tendon’s mechanical properties and its ability to bear loads… Continue reading.
There are myriad ways in which people can experience physical wounds – from minor scrapes and abrasions to the effects of surgery, critical injuries, burns and other major traumas. The healing process for these wounds can also vary among individuals and may be adversely affected by underlying health conditions such as vascular insufficiencies, diabetes, obesity and advanced age. In severe cases, abnormal wound healing processes can result in chronic wounds, a condition which can dramatically affect mobility, quality of life and healthcare costs.
The normal wound healing process involves a complex series of four overlapping but distinct steps. During the initial steps, platelets from the blood control bleeding by signaling the formation of a protein matrix plug; they also generate molecules that will constrict blood vessels and mobilize other types of cells to the site. These additional cells kill pathogens in the wound area and trigger wound healing and blood vessel formation. In later steps, the protein matrix, blood vessel growth and connections are even further developed, and skin and other surface cells begin to migrate to the site. Together, the skin and protein matrix form granulation tissue to repair and close the wound. In the final step, blood vessel formation tapers and the granulation tissue continue to develop until it eventually becomes a scar… Continue reading.
From wide-ranging body movements as minute as a pulse to the various movements of joints, muscles and limbs, wearable pressure sensors placed directly on the skin may be used in myriad ways to monitor health. Other types of skin sensors can monitor health indicators through measurement of sweat and temperature on the skin’s surface.
These capabilities translate into useful medical applications, such as in monitoring motor-control diseases like Parkinson’s disease, evaluating movements in athletes, or in monitoring physical or even emotional parameters through measurements of the skin’s moisture. Other examples of game-changing skin-sensing devices include skin sensors to monitor stress levels in autistic children (who have trouble with emotional expression) and tactile sensors that can assist patients with recovering motor skills after a stroke… Continue reading.
Following surgery within the abdominal or pelvic cavities, scar tissue often forms on the inner linings of these cavities and may adhere to the organs which are found within them. This adhesion occurs in 93% of these patients and can affect the intestines, liver, urinary bladder, gall bladder and female reproductive organs. In up to 20% of adhesion cases, serious complications can arise, including chronic abdominal or pelvic pain, fertility problems or intestinal obstruction. This not only results in increased patient suffering and mortality but adds over $1 billion in additional hospital costs in the United States alone.
A commonly used method of combating this problem is to use commercially available synthetic films as adhesion barriers. However, there are sometimes difficulties in applying these films with a sufficient degree of conformity to irregular surfaces and they can also be fragile and difficult to handle. Additionally, it is not possible to use the films for small-portal procedures such as catheterization and laparoscopies, and their overall efficacy is estimated at 25%… Continue reading.
Today’s nanoscale technologies are sophisticated enough to be applied in an endless number of useful devices, from sensors in touch screen devices and household appliances to wearable biosensors that can monitor chemical levels in our blood, muscle movement, breathing and pulse rate. In addition, there are technologies for precision devices such as high-resolution scanning probe microscopes which enable one to visualize surfaces not only at the atomic level, but even the individual atoms themselves.
These devices typically utilize electrodes which are made by applying thin coatings of conductive materials onto glass or ceramic substrates. However, these types of electrodes are fragile and lack flexibility, and they can involve costly and limited materials as well as difficult fabrication methods… Continue reading.
Using artificial intelligence technology, Terasaki Institute for Biomedical Innovation (TIBI) researchers developed and validated an image-based detection model for COVID-19. The model analyzes lung images and can detect COVID-19 infection.
Medical imaging has become an important tool in the diagnosis and prognostic assessments of diseases. In recent years, artificial intelligence models have been implemented with imaging technology to improve diagnostic capabilities. In comporting AI into imaging technology, models can reveal disease characteristics that are not visible to the naked eye… Continue reading.
The interstitial fluid is a major component of the liquid environment in the body and fills the spaces between the body’s cells. In contrast, blood circulates only within the circulatory vessels of the body and is composed of blood cells and the liquid part of the blood, plasma. Both fluids contain special components called biomarkers, which are valuable indicators of bodily health. These biomarkers include various types of molecules such as proteins, hormones or DNA, and can also include drugs and metabolites.
When monitoring patient health, the standard source for the measurement of biomarkers is blood. Samples are drawn by venous puncture, most often from the forearm or from the veins in the hand. Occasionally there are problems in drawing blood when the veins are subject to collapse, or when they are very small or difficult to locate. Still other problems may occur when the veins “roll” or move from side to side. And as in any procedure that involves a wound to the skin, there is always the risk of infection that is introduced. The problems are compounded when patients are required to submit multiple samples over time… Continue reading.
Cartilage is far from being like cartilage. As a rubber-like elastic tissue with widely varying properties, it lubricates our joints to keep them healthy and in motion, and forms many of our internal structures such as the intervertebral discs in our spine, the flexible connections between our ribs, and our voice box, as well as external tissues like nose, and ears.
Specifically, in joints, the wear-and-tear of cartilage over time eventually can result in the painful bone-on-bone contacts, and the bone damage and inflammatory reactions that plague patients with osteoarthritis, the most common form of arthritis. In the US alone, 32.5 million adults are affected by osteoarthritis, and thus far there is no strategy that allows lasting repair or replacement of degenerating joint (articular) cartilage… Continue reading.
A team of Brigham and Women’s Hospital researchers have developed a way to bioprint tubular structures that better mimic native vessels and ducts in the body. The 3-D bioprinting technique allows fine-tuning of the printed tissues’ properties, such as number of layers and ability to transport nutrients. These more complex tissues offer potentially viable replacements for damaged tissue. The team describes its new approach and results in a paper published on Aug. 23 in Advanced Materials.
“The vessels in the body are not uniform,” said Yu Shrike Zhang, PhD, senior author on the study and an associate bioengineer in BWH’s Department of Medicine. “This bioprinting method generates complex tubular structures that mimic those in the human system with higher fidelity than previous techniques.”
Many disorders damage tubular tissues: arteritis, atherosclerosis and thrombosis damage blood vessels, while urothelial tissue can suffer inflammatory lesions and deleterious congenital anomalies… Continue reading.
A UCLA bioengineer has developed a technique that uses a specially adapted 3D printer to build therapeutic biomaterials from multiple materials. The advance could be a step toward on-demand printing of complex artificial tissues for use in transplants and other surgeries.
“Tissues are wonderfully complex structures, so to engineer artificial versions of them that function properly, we have to recreate their complexity,” said Ali Khademhosseini, who led the study and is UCLA’s Levi James Knight, Jr., Professor of Engineering at the UCLA Samueli School of Engineering. “Our new approach offers a way to build complex biocompatible structures made from different materials.”
The study was published in Advanced Materials.
The technique uses a light-based process called stereolithography, and it takes advantage of a customized 3D printer designed by Khademhosseini that has two key components. The first is a custom-built microfluidic chip — a small, flat platform similar in size to a computer chip — with multiple inlets that each “prints” a different material. The other component is a digital micromirror, an array of more than a million tiny mirrors that each moves independently… Continue reading.
He was born in Iran and lived there during the turbulence of the Iranian Revolution and the Iran-Iraq War. When he was young, Khademhosseini’s parents decided to move their family to Canada, in part because of the danger from the ongoing war, but also to offer a better future for Khademhosseini and his brother.
“In my school in Toronto,” said Khademhosseini, “literally every person was from a different country. We saw people from all over the place all come together so you really start to appreciate that people are more similar than different.”
Khademhosseini gained his first experience in lab work as an undergraduate at the University of Toronto. There he met Dr. Michael Sefton, whom he credits for exposing him to tissue engineering science. “They were encapsulating pancreatic cells in a polymer coating to try to make it inert to the body’s immune system, so you could take cells from pigs, for example, and be able to put it in people. I really fell in love with that research right off the bat. I said, okay, this is something that can have a real impact on how health care is performed… Continue reading.
Small blood clots called emboli are mostly known for traveling through the vasculature before they lodge and obstruct vessels, impeding blood and oxygen supply to organs such as the lung. To stop excessive bleeding or the flow of blood into an aneurysm, clinicians harness the same principle by forming artificial therapeutic emboli that can plug blood-carrying vessels. Using steerable catheters, they place tiny soft-metal coils or liquid embolic agents (“glues”) into the affected artery to block the passage of blood.
However, both procedures come with problems and risks. Coil embolization can be ineffective if the coil is not positioned or seized accurately, and coils need efficient blood clotting in patients to be stabilized. Liquid embolic agents, on the other hand, can be accidentally cemented to catheters or non-targeted areas due to insufficient control of their solidification. And, importantly, both types of emboli can become leaky over time.
A team of researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering, Brigham and Women’s Hospital, the Mayo Clinic, and MIT now describe a new class of hydrogel-based embolic agents that could help eliminate all these drawbacks. Their study, published in Science Translational Medicine, provides proof of concept and first preclinical evidence in animal models that the shear-controlled hydrogel can be delivered by catheters and injected into blood vessels to form robust and safe blockages.
“This new approach to vascular embolization is based on a hydrogel composite with phase properties we can reliably control with mechanical pressure. It completely blocks vessels in situations where other methods can fail, such as in vascular areas that are highly convoluted or subject to unusual blood pressures, and, importantly, it still works when normal blood coagulation is impaired, like in patients receiving blood thinners or suffering from an intrinsic inability to efficiently form blood clots,” said Ali Khademhosseini, an associate faculty member of the Wyss Institute, and a professor at Harvard-MIT’s Division of Health Sciences and Technology and Brigham and Women’s Hospital.
In 2014, Khademhosseini, together with MIT Associate Professor Bradley Olsen, also an author on the present study, reported the so-called shear-thinning biomaterial (STB) and demonstrated that, when applied in bulk to larger wound surfaces, it can seal them off to halt bleeding.
A 5-year, $2 million grant from the National Institutes of Health will allow researchers at Case Western Reserve University and Harvard University to build a microfactory that churns out a formula to produce joint cartilage.
The end product could one day benefit many of the tens of millions of people in the United States who suffer from cartilage loss or damage.
Articular cartilage coats the ends of long bones, bearing loads, absorbing shocks and, with sunovial fluid, enabling knees, hips and shoulders to smoothly bend, lift and rotate. Since the tissue has little ability to repair or heal itself, there is a critical need for new therapeutic strategies.
Artificial substitutes can’t match the real thing, and efforts to engineer articular cartilage have been stymied by the complex process of turning stem cells into the desired tissue.
“Cells are very responsive to cues presented to them from their surroundings,” said Eben Alsberg, professor of biomedical engineering and orthopedic surgery at Case Western Reserve. “We hope to learn what signals can steer stem cell behavior with the ultimate goal of engineering cartilage quickly with the functionality of natural tissue,”
He’s teaming with Ali Khademhosseini, a professor at Harvard-MIT’s Division of Health Sciences and Technology, on the research.
“We will do a systematic study of the effects of cellular microenvironmental factors on cellular differentiation and cartilage formation,” Khademhosseini said Alsberg has previously coaxed stem cells obtained from adult bone marrow and fat tissue into cartilage. His lab has designed an array of new materials with controllable characteristics, such as physical properties, cell adhesive properties and the capacity to control the delivery of bioactive factors.
By controlling the presentation of these signals to cells, both independently and in combination, along with the regulated presentation of mechanical signals, his group aims to identify key cues that are important for changing stem cells into cartilage-producing cells.
Khademhosseini is an expert in microfabrication, and his lab specializes in developing micro- and nano-scale technologies to control cell behavior. He will develop a microscale high-throughput system at his lab that will speed testing and analysis of materials engineered in Alsberg’s lab.
Brigham and Women’s Hospital (BWH) bioengineers have a developed a unique hydrogel whose properties could provide significant benefits in wound healing. The BWH Biomedical Engineering Division team, led by biomedical engineer Ali Khademhosseini, PhD, MASc, and chemical engineer Nasim Annabi, PhD, reported their findings in the July 1, 2015, online edition of Advanced Functional Materials.
“Hydrogels are widely used in biomedicine, but currently available materials have limitations,” says Khademhosseini, study senior author and Director of the BWH Biomaterials Innovation Research Center. “Some synthetic gels degrade into toxic chemicals over time, and some natural gels are not strong enough to withstand the flow of arterial blood through them.”
While tissue engineers have made strides in making complex artificial tissues, such as those of the heart, liver and lungs, creating artificial blood vessels has remained a critical challenge in tissue engineering. The tangled highway of blood vessels that twists and turns inside our bodies performs the crucial task of delivering essential nutrients and disposing hazardous waste to keep our organs working properly. To successfully regenerate organs, tissue engineers will need to make artificial blood vessels as well as organ tissues.
In this video, Ali Khademhosseini, PhD, MASc, a biomedical engineer and the Director of the BWH Biomaterials Innovation Research Center, talks about progress in fabricating blood vessels by using this 3-D bioprinting technique. The first transplantable structures will likely be parts of organs, such as a replacement for heart muscle damaged by myocardial infarction. Dr. Khademhosseini envisions that the same technology will lead to the replacement of bone tissue. He also notes that in the future, 3-D printing technology may be used to develop transplantable tissues customized to each patient’s needs or be used outside the body to develop drugs that are safe and effective.
A team of researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University has found a way to self-assemble complex structures out of bricks smaller than a grain of salt. The self-assembly method could help solve one of the major challenges in tissue engineering: regrowing human tissue by injecting tiny components into the body that then self-assemble into larger, intricately structured, biocompatible scaffolds at an injury site.
The key to self-assembly was developing the world’s first programmable glue. The glue is made of DNA, and it directs specific bricks of a water-filled gel to stick only to each other, the scientists report in the September 9th online issue of Nature Communications.
"By using DNA glue to guide gel bricks to self-assemble, we’re creating sophisticated programmable architecture," says Peng Yin, Ph.D., a Core Faculty member at the Wyss Institute and senior coauthor of the study, who is also an Assistant Professor of Systems Biology at Harvard Medical School. This novel self-assembly method worked for gel bricks from as small as a speck of silt (30 microns diameter) to as large as a grain of sand (1 millimeter diameter), underscoring the method’s versatility.
The programmable DNA glue could also be used with other materials to create a variety of small, self-assembling devices, including lenses, reconfigurable microchips, and surgical glue that could knit together only the desired tissues, said Ali Khademhosseini, Ph.D., an Associate Faculty member at the Wyss Institute who is the other senior coauthor of the study.
Ali Khademhosseni, PhD, the principal investigator in the Khademhosseini Laboratory in BWH’s Department of Biomedical Engineering, received the 2013 Technical Achievement Award from the IEEE Engineering in Medicine and Biology Society (EMBS). The award will be presented at the EMBS’s annual meeting in July in Japan.
The Technical Achievement Award recognizes individuals who have made outstanding achievements in, contributions to and innovation in a technical area of biomedical engineering. Khademhosseini is being recognized for contributions at the interface between engineering, biomaterials and biological sciences, especially applications of micro- and nanoengineered biomaterials for regenerative medicine.
The IEEE EMBS aims to advance medicine and biology through the application of engineering sciences and technology, promote the profession of biomedical engineering, establish technical standards and provide global leadership for the field of biomedical engineering.
Researchers from Harvard-affiliated Brigham and Women’s Hospital (BWH) are the first to report that synthetic silicate nanoplatelets (also known as layered clay) can induce stem cells to become bone cells without the need of additional bone-inducing factors. Synthetic silicates are made up of simple or complex salts of silicic acids, and have been used extensively for various commercial and industrial applications, such as food additives, glass and ceramic fillers, and anti-caking agents.
The research was published online Monday in Advanced Materials.
“With an aging population in the U.S., injuries and degenerative conditions are subsequently on the rise,” said Harvard Medical School Associate Professor of Medicine Ali Khademhosseini of the BWH Division of Biomedical Engineering, the senior author of the study. “As a result, there is an increased demand for therapies that can repair damaged tissues. In particular, there is a great need for new materials that can direct stem cell differentiation and facilitate functional tissue formation. Silicate nanoplatelets have the potential to address this need in medicine and biotechnology.”
A team of bioengineers at Brigham and Women’s Hospital (BWH) is the first to report creating artificial heart tissue that closely mimics the functions of natural heart tissue through the use of human-based materials. Their work will advance how clinicians treat the damaging effects caused by heart disease, the leading cause of death in the United States
Ali Khademhosseini, PhD, principal investigator in the Khademhosseini Laboratory in the Division of Biomedical Engineering in BWH’s Department of Medicine, received the Young Investigator Award from the Controlled Release Society. The award recognizes a member of the Controlled Release Society under age 40 who has made outstanding contributions to the science of controlled release and drug delivery.
He was also recently selected to serve as a permanent member of the Bioengineering Technology and Surgical Studies section of the Center for Scientific Review.
Tissue Engineering: New nanotube-based scaffold mimics heart tissue’s electrical and mechanical properties
Heart attacks kill muscle cells called cardiomyocytes, leaving behind tissue damage. If scientists could grow cardiac tissue in the lab, they could perhaps graft patches of healthy tissue onto a patient’s damaged heart. A new carbon nanotube-studded hydrogel acts as a scaffold for growing cardiac tissue that beats spontaneously (ACS Nano, DOI: 10.1021/nn305559j).
One challenge for growing heart tissue in the lab is finding a material that simulates the environment of the heart, says Ali Khademhosseini, a bioengineer at Harvard Medical School. For the tissue to function properly, it needs a scaffold that is electrically conductive to transmit the cell-to-cell signals that regulate muscle contractions. The material also must be mechanically strong to withstand repeated contractions.
Hybrid materials made of cardiac cells and carbon nanotubes might patch damaged hearts and provide muscle for robots made of living tissues.
The tissues of the heart are mechanically tough and electrically conductive, and they keep a strong, rhythmic beat—properties that are tough to mimic in the lab. But a new hybrid material that combines cell-friendly gel, strong, conductive carbon nanotubes, and living cardiac cells mimics natural heart tissue more successfully than previous attempts. Eventually the new material could be useful in both medical and robotic applications.
The bionic tissues, made by Ali Khademhosseini, a professor at the Harvard-MIT Division of Health Sciences and Technology in Cambridge, Massachusetts, could serve as muscles for biological machines—moving, programmable living tissues that take synthetic biology beyond single cells. A lot of the things that natural tissues and biological cells can do, such as sense and respond to their environment, are hard for engineers to achieve with the synthetic materials used in conventional robotics. Researchers hope that building machines from biological materials like heart tissue will expand what’s possible. The new tissues can swim untethered in water, swing back and forth, and perform other moves programmed by controlling their shape and thickness.
The Editors of the Biochemical Engineering Journal, in partnership with the Food, Pharmaceutical and Bioengineering Division of AIChE, are very pleased to announce the selection of Ali Khademhosseini as the recipient of the third Biochemical Engineering Journal Young Investigator Award. This award recognizes outstanding excellence in research and practice contributed to the field of biochemical engineering by a young community member.
In March 2012, the Executive Editorial Board of Polymer International and the IUPAC Polymer Division announced that Ali Khademhosseini (MIT and Harvard) was the third winner of the Polymer International-IUPAC Award for Creativity in Applied Polymer Science or Polymer Technology. Khademhosseini’s research has opened up new ways of using biomaterials to make tissues with controlled vascularization as well as tissue architecture.
Two scientists from The University of Texas at Austin are among the 2011 recipients of Presidential Early Career Awards for Scientists and Engineers (PECASE), the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers.
The recipients are Ali Khademhosseini, a 2011 Donald D. Harrington Faculty Fellow in the Cockrell School of Engineering’s Biomedical Engineering Department, and Sara Sawyer, assistant professor of molecular genetics and microbiology and member of the Institute for Cellular and Molecular Biology in the College of Natural Sciences.
Tiny particles made of polymers hold great promise for targeted delivery of drugs and as structural scaffolds for building artificial tissues. However, current production methods for such microparticles yield a limited array of shapes and can only be made with certain materials, restricting their usefulness.
In an advance that could broadly expand the possible applications for such particles, MIT engineers have developed a way to make microparticles of nearly any shape, using a micromold that changes shape in response to temperature. They can also precisely place drugs into different compartments of the particles, making it easier to control the timing of drug release, or arrange different cells into layers to create tissue that closely mimics the structure of natural tissues.
The new technique, described in a paper published online July 18 in the Journal of the American Chemical Society, also allows researchers to create microparticles from a much more diverse range of materials, says Halil Tekin, an MIT graduate student in electrical engineering and computer science and lead author of the paper.
Currently, most drug-delivering particles and cell-encapsulating microgels are created using photolithography, which relies on ultraviolet light to transform liquid polymers into a solid gel. However, this technique can be used only with certain materials, such as polyethylene glycol (PEG), and the ultraviolet light may harm cells.
Another way to create microparticles is to fill a tiny mold with a liquid gel carrying drug molecules or cells, then cool it until it sets into the desired shape. However, this does not allow for creation of multiple layers.
The MIT research team, led by Ali Khademhosseini, associate professor in the MIT-Harvard Division of Health Sciences and Technology, and Robert Langer, the David H. Koch Institute Professor, overcame that obstacle by building micromolds out of a temperature-sensitive material that shrinks when heated.