As shortages of personal protective equipment persist during the coronavirus pandemic, 3D printing has helped to alleviate some of the gaps. But Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, and his team are using the process in a more innovative way: creating tiny replicas of human organs — some as small as a pinhead — to test drugs to fight COVID-19.
The team is constructing miniature lungs and colons — two organs particularly affected by the coronavirus — then sending them overnight by courier for testing at a biosafety lab at George Mason University in Fairfax, Virginia. While they initially created some of the organoids by hand using a pipette, they are beginning to print these at scale for research as the pandemic continues to surge.
In the last few years, Atala’s institute had already printed these tiny clusters of cells to test drug efficacy against bacteria and infectious diseases like the Zika virus, “but we never thought we’d be considering this for a pandemic,” he said. His team has the ability to print “thousands an hour,” he said from his lab in Winston-Salem, North Carolina.
The process of constructing human tissue this way is a form of bioprinting. While its use in humans is still years away, researchers are honing the methods to test drugs and, eventually, to create skin and full-size organs for transplanting. Researchers are making strides in printing skin, critical for burn victims; managing diseases like diabetes in which wound healing is difficult; and for the testing of cosmetics without harming animals, or, of course, humans.
“Even to us it sometimes seems like science fiction,” said Akhilesh Gaharwar, who directs a cross-disciplinary lab in the biomedical engineering department at Texas A&M University that focuses on bioprinting and other approaches to regenerative medicine.
Bioprinting’s importance for pharmaceutical analysis is paramount now, not only for potential COVID-19 treatments but also for testing treatments for cancer and other diseases. Atala says that the organoids allow researchers to analyze a drug’s effect on an organ “without the noise” of an individual’s metabolism.
He cited Rezulin, a popular diabetes drug recalled in 2000 after there was evidence of liver failure. His lab tested an archived version of the drug, and Atala said that within two weeks, the liver toxicity became apparent. What accounts for the difference? An organoid replicates an organ in its purest form and offers data points that might not occur in clinical trials, he said, adding that the testing is additive to, rather than in lieu of, clinical trials.
Testing on bioprinted skin or other miniature organs also can more readily determine which drugs that work in animals like rats might not perform well in people.
“The 3D models can circumvent animal testing and make the pathway stronger from the lab to the clinic,” Gaharwar said. That has importance for consumer goods as well as pharmaceuticals; since 2013, the European Union, for example, has prohibited cosmetics companies from testing products on animals.
The foundation for a printed organ is known as a scaffold, made of biodegradable materials. To provide nutrition for the organoid, microscopic channels only 50 microns in diameter — roughly half the size of a human hair — are included in the scaffold. Once completed, the “bioink,” a liquid combination of cells and hydrogel that turns into gelatin, is then printed onto the scaffold “like a layer cake,” Atala said.
Another important part of the process is constructing blood vessels as part of the printing. Pankaj Karande, an assistant professor of chemical and biological engineering at Rensselaer Polytechnic Institute, has been experimenting with skin printing since 2014 and recently had success in this step.
Using a cell known as a fibroblast, which helps with growth, along with collagen, as a scaffold, researchers at the institute printed the epidermis and dermis, the first two layers of skin. (The hypodermis is the third layer.) “It turns out the skin cells don’t mind being sheared,” Karande said, and they could ultimately survive.
But their work hit a snag: Without incorporating blood vessels, the skin eventually sloughs off. Collaborating with Jordan Pober and W. Mark Saltzman of Yale University, they eventually succeeded in constructing all three layers of human skin as well as vasculature, or blood vessels, which Karande said was essential to the skin’s surviving after it had been grafted.
The three began experimenting with integrating human endothelial cells, which line blood vessels, and human pericyte cells, which surround the endothelial cells, into the skin as it was printed. Eventually, after much trial and error, they were able to integrate the blood vessels with the skin and found that connections were formed between new and existing blood vessels.
While the work is preliminary — tested in mice — Karande said he was hopeful that the success in printing integrated skin and vasculature would set the stage for successful grafting in humans eventually.
The research, according to Karande, is painstaking and involves a lot of trial and error. “We have Plan A, which we often know won’t work, and then we go down the list. We can often write about what works in five pages but have 5,000 pages of what didn’t work,” he added.
-The New York Times Company-
CHICAGO - Moderna Inc on Thursday confirmed it plans to start a trial of 30,000 volunteers of its much-anticipated coronavirus vaccine in July as the company enters the final stage of testing.
The Cambridge, Massachusetts-based biotech said the primary goal of the study would be to prevent symptomatic COVID-19, the disease caused by the novel coronavirus. The key secondary goal would be prevention of severe disease, as defined by keeping people out of the hospital.
The company's shares jumped 6 percent in premarket trading.
Moderna said it has selected the 100-microgram dose of the vaccine for the late-stage study. At that dose level, the company is on track to deliver about 500 million doses per year, and possibly up to 1 billion doses per year, starting in 2021 from the company's internal US manufacturing site and strategic collaboration with Swiss drugmaker Lonza.
The company said it chose the 100-microgram dose to maximize the immune response and minimize adverse reactions.
Moderna said is has completed manufacturing of enough vaccine to start the phase 3 trial.
In the midstage study, the company said it has enrolled 300 healthy adults, who have each been dosed with at least one shot, as well as the first 50 older adults, aged 18 to 54.
Testing the vaccine in older adults will be critical because this group is at higher risk for the most severe effects of the virus, and older adults typically have less efficient immune function. The midstage study is testing the safety and preliminary effectiveness of 2 doses of the vaccine given 28 days apart.
Study participants will be followed for a year.
-reuters-
Gilead Sciences Inc's antiviral drug, remdesivir, prevented lung disease in macaque monkeys infected with the new coronavirus, a study published in medical journal Nature showed on Tuesday.
Remdesivir is the first drug to show improvement in COVID-19 in human trials, and its progress in clinical studies is being closely watched as nations look for a treatment for the disease, which has infected more than 7 million people and killed over 400,000.
In the study, 12 macaque monkeys were deliberately infected with the new coronavirus, and half of them were given early treatment with remdesivir.
Macaques that received remdesivir did not show signs of respiratory disease and had reduced damage to the lungs, according to the study. https://go.nature.com/2Yj9xq2
Details from the trial in monkeys were previously released by the US National Institutes of Health in April, but those findings were not reviewed by peers - a step that validates a research study.
The authors of the study suggested that remdesivir should be considered as a treatment as early as possible to prevent progression to pneumonia in COVID-19 patients.
Remdesivir has been cleared for emergency use in severely-ill patients in the United States, India and South Korea. Some European nations are also using it under compassionate programs.
Trials of the drug in humans are ongoing, and early data has shown the drug helped patients recover more quickly from the illness caused by the new coronavirus.
-reuters-
LONDON - United Nations Secretary General Antonio Guterres on Thursday said a new vaccine against the coronavirus had to be available to everyone across the world, as an international conference got under way to raise funds for new life-saving treatments.
The virtual meeting, hosted by Britain, aims to raise $7.4 billion for immunization programs stalled by the pandemic, and launch a new fundraising drive to support potential COVID-19 vaccines.
In a video message, Guterres said: "A vaccine must be seen as a global public good -- a people's vaccine, which a growing number of world leaders are calling for."
There needed to be "global solidarity to ensure that every person, everywhere, has access," he added.
British Prime Minister Boris Johnson called for a "new era of global health cooperation" to "unite humanity in the fight against disease," particularly in the poorest countries.
More than 50 countries are taking part in the meeting, as well as individuals such as billionaire philanthropist Bill Gates, to raise funds for Gavi, the vaccine alliance.
Over the next 5 years, it wants to reboot halted programs and provide vaccines at a much-reduced cost to some 300 million children worldwide.
Gavi and its partners will also launch a financing drive to purchase potential COVID-19 vaccines, scale-up their production and support delivery to developing nations.
The pandemic has exposed new ruptures in international cooperation, notably with US President Donald Trump's decision to pull out of the World Health Organization (WHO).
But Johnson said helping developing countries would benefit places such as Britain, which has seen more than 39,000 deaths in the coronavirus outbreak -- the second-highest in the world behind the United States.
"This support for routine immunizations will shore up poorer countries' health care systems to deal with coronavirus -- and so help to stop the global spread," he told reporters on Wednesday.
"This virus has shown how connected we are. We're fighting an invisible enemy. And no one is safe frankly until we are all safe."
ALL AT RISK
Trump sent a recorded message to the conference, telling delegates: "As the coronavirus has shown, there are no borders. It doesn't discriminate.
"It's mean, it's nasty. But we can all take care of it together... we will work hard. We will work strong."
Microsoft founder Gates earlier said pharmaceutical companies had been working together to try to secure the required production capacity.
"It's been amazing, the pharmaceutical companies stepping up to say 'yes, even if our vaccine is not the best, we will make our factories available,'" he told BBC radio.
The coronavirus pandemic has killed more than 380,000 people since it emerged in China last December, according to an AFP tally of official sources.
Stay-at-home orders were imposed across the world, causing huge economic disruption and the suspension of many routine immunisation services.
The WHO, UN children's agency UNICEF and Gavi warned last month that vaccine services were disrupted in nearly 70 countries, affecting some 80 million children under the age of 1.
Polio eradication drives were suspended in dozens of countries, while measles vaccination campaigns were also put on hold in 27 countries, UNICEF said.
Guterres urged the conference to commit to finding "safe ways to continue delivering vaccinations, even as COVID-19 spreads" and to make sure that any coronavirus vaccine "reaches everyone".
Recent Gavi-supported modelling from the London School of Hygiene and Tropical Medicine estimated that for every coronavirus death prevented by halting vaccination campaigns in Africa, up to 140 people could die from vaccine-preventable diseases.
"More children in more countries are now protected against more diseases than at any point in history," said Seth Berkley, chief executive of Gavi.
"However, these historic advances in global health are now at risk of unravelling as COVID-19 causes unprecedented disruption to vaccine programs worldwide.
"We face the very real prospect of a global resurgence of diseases like measles, polio and yellow fever, which would put us all at risk."
Agence France-Presse
SEOUL - Two elderly South Korean coronavirus patients recovered from severe pneumonia after being treated with plasma from survivors, researchers said Tuesday, offering hope in the face of the global pandemic.
Scientists have pointed to the potential benefits of plasma -- a blood fluid -- from recovered individuals who have developed antibodies to the virus enabling the body's defenses to attack it.
Since emerging in China in December, the coronavirus has killed almost 75,000 people as drugmakers worldwide race to develop a vaccine and treatments for the disease.
Plasma therapy could become "an alternative treatment for patients in critical condition who do not respond to antiviral drugs," said Choi Jun-yong, a doctor and researcher at Severance Hospital in Seoul, where both patients were treated.
But large-scale clinical trials were needed to prove its effectiveness, he added.
One of the 2 patients was a 71-year-old man with no underlying conditions who only improved when treated with plasma from a recovered patient in his 20s, along with steroids.
He was initially given malaria drugs and a respirator for severe pneumonia.
The other patient, a 67-year-old female, also did not respond to initial treatments including malaria, HIV drugs, and oxygen therapy. She began to recover after receiving plasma therapy and steroids at the same time, researchers said.
Their findings were published in the peer-reviewed Journal of Korean Medicine.
Kwon Jun-wook, an official at Seoul's Central Disease Control Headquarters, said plasma therapy was "important" when there was "currently no vaccine or treatment available" for the virus.
He called on experts to examine the 2 cases urgently.
Research on plasma and other therapies "will proceed quickly," Kwon added.
Small studies on plasma have demonstrated its effectiveness in treating infectious diseases, including Ebola and SARS.
Trials started in France on Tuesday involving 60 patients in Paris hospitals, half of whom will receive plasma from recovered patients.
The US Food and Drug Administration authorized physicians to experiment with the strategy to fight the coronavirus, and tests are also being carried out in China.
South Korea endured one of the worst early outbreaks of the virus, but appears to have brought it under control thanks to its extensive "trace, test and treat" program.
Agence France-Presse
