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3D Printing for Organ Transplants?

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The use of 3D printers in the medical and dentistry field is vastly growing from dental implants to prosthetics, and models for surgeons to practice on before making cuts on a patient. Researchers have advanced past printing with plastics and metals to printing with cells that form into living human tissues. Although no one has printed fully functional transplantable human organs, scientists are making improvements. Researchers have been developing pieces of human tissue that can be used to test drugs and creating methods to succeed in the challenges of recreating the body’s complex biology. This article will explore some of the milestones achieved by research groups as well as some of the challenges they have faced on the journey to creating 3D printed organs. 

Cardiac Cells and Ear Transplants

Thus far, scientists have printed mini organoids and microfluidic models of tissues that are also known as organs on chips. The results from both microfluidics and organoids show encouraging insights into operating like the human body. Pharmaceutical companies created the models and are testing drugs before moving into animal studies, after which they will be moving to clinical trials. One group involved in the clinical trials printed cardiac cells on a chip and attached the cells to a bioreactor before testing the cardiac toxicity of a commonly known cancer drug, doxorubicin. The team revealed that the cells’ beating rate reduced significantly after exposure to the medication

Robby Bowles, a bioengineer at the University of Utah, stated that other companies had been involved with 3D printing. The companies studied printing 3D ears, transplanting the ears to children who had congenital disabilities such as underdevelopment of the ears. He acknowledged initial attempts of using 3D printing in the medical field. 

Organovo Studies 

Most recently, researchers have built patches of tissues that emulate fractions of particular organs but haven’t been able to replicate the complexity or cell density of a full organ. Some studies show that even a patch of human tissue could be useful for treatment in patients. However, Organovo, a company that announced its program to design 3D printed liver tissue for human transplants, revealed the results from a previous study. The company presented a successful live implant in a mouse model of genetic liver disease which raised multiple biomarkers that showed improvement in liver function

Researchers have also made progress with one of the biggest challenges in printing 3D organs by creating blood vessels or arranging of blood vessels in an organ, also known as vasculature. After patches were implanted into the mouse’s liver in the Organovo study, blood was supplied to it by the surrounding liver tissue. Still, an entire organ would need to be prepared for blood flow. 

Wyss Institute 

In 2018, Sébastian Uzel, Mark Skylar-Scott, and a team at the Wyss Institute were able to 3D print a tiny, beating heart ventricle complete with blood vessels. A few days later after printing the tissue, Uzel says he came into the lab and found a piece of tissue twitching, that was “very terrifying and exciting.”

The team used embedded printing rather than printing the veins in layers, a method in which instead of building from the bottom of a slide upwards, materials are released directly into a bath or matrix. This approach allows researchers to print “free form in 3D,” according to Skylar-Scott, instead of having to print a vascular tree. The matrix, in this case, was cellular material that made up the heart ventricle. This material, a gelatin-like ink, pushed these cells gently out of the way to create a network of channels. Once the printing was completed, the combination was then heated up. This heat caused the cellular matrix to solidify but caused the gelatin to liquify so it could then be washed out, leaving room for blood to flow through.  

Challenges

Though there are many advancements in 3D printing organs, scientists remain “a ways away” from printing more intricate tissues and organs that can be transplanted into living organisms, but this is the objective for many scientists to achieve soon according to Bowles. As reported by the United Network for Organ Sharing, there are over 112,000 people in the US waiting for an organ transplant, and 20 of those waiting die each day

For a long time, biological engineers have attempted to construct 3D structures that they could seed among stem cells that could later develop and form into organs. One reason this could be challenging according to Bowles “to a large extent don’t allow you to introduce the kind of the organization of gradients and the patterning that is in the tissue,”. Bowles also says “there is no control over where the cells go in that tissue.” In contrast to 3D printing which provides researchers with the ability to precisely direct the organization of the cells that could guide better control over organ development.

Another important aspect is that 3D printed organs would need to be created from cells that the patient’s immune system could identify as its own to prevent immune rejection and the need for patients to be prescribed immunosuppressive medication. 3D printed organs could be developed from patient-specific induced pluripotent stem cells. However, the difficult aspect is getting the cells to differentiate into the subtype of mature cells required to form a specific organ. Bowles believes that “the difficulty is kind of coming together and producing complex patternings of cells and biomaterials together to produce different functions of the different tissues and organs.”.

Potential Solutions Moving Forward

To accomplish the emulation of patterns shown in vivo, there are still other methods scientists would have to develop. Scientists can print cells into hydrogels or different environments along with molecular signals and gradients built to influence the cells into arranging themselves into lifelike organs. 3D printing can be used by scientists to create these hydrogels as well. 

In the meantime, 3D printing of tissues is helping to expedite basic and clinical research regarding the human body. Though challenges associated with 3D printing remain, it has great potential to create organs and provide lifesaving organ transplants to patients. The advancement of the 3D printing continues to show promising results that could one day be effective in treating patients with critical conditions.

Sources: 

  1. https://www.the-scientist.com/news-opinion/on-the-road-to-3-d-printed-organs-67187?_ga=2.230604892.1926843048.1587572466-1658288134.1587572466
  2. https://organovo.com/wp-content/uploads/2019/01/ORG-AASLD2017-805_THX_VJ-FINAL.pdf
  3. https://unos.org/data/transplant-trends/
  4. https://www.bme.utah.edu/department-directory/#/filter-Faculty
  5. https://bioe.uic.edu/profiles/alsberg-eben/
  6. https://www.prellisbio.com/team
  7. https://lewisgroup.seas.harvard.edu/people/mark-skylar-scott
  8. https://lewisgroup.seas.harvard.edu/people/s%C3%A9bastien-g-m-uzel
  9. https://advances.sciencemag.org/content/5/9/eaaw2459

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Covid-19

WOH Series Part 2: Current treatments for COVID-19

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Patients diagnosed with the coronavirus are receiving different care depending on the severity of their symptoms. Current healthcare facilities are in clinical trials with possible antiviral drugs that could be used as a treatment, such as remdesivir. Even plasma from recovered patients is being considered for a potential treatment for COVID-19 patients. If respiratory problems caused by the virus persist, healthcare professionals are turning to ventilators to help patients breathe and fight for their lives. Researchers are currently evaluating the effectiveness of these treatments to determine which care is suited for various patients with mild to severe symptoms. 

One drug that is the furthest along in clinical trials for treating COVID-19 is remdesivir. Researchers are also testing older medications that are typically used to treat other conditions to see if they are also useful in treating COVID-19. 

Remdesivir

This antiviral drug is administered by intravenous (IV) infusion in the hospital. Remdesivir is a new drug that has been given an “emergency use authorization.” Previously, the drug showed to have some effect against SARS, MERS, and Ebola in cell and animal models

Based on the positive reports from studies, the FDA issued an emergency use authorization (EUA) for remdesivir on May 1, 2020. The EUA does not mean that the FDA has approved remdesivir for the treatment of COVID-19. Instead, the EUA intends to make it easier for doctors to get remdesivir for hospitalized patients with severe COVID-19 symptoms. These are patients who require mechanical ventilation or extra oxygen

Hydroxychloroquine and chloroquine

Hydroxychloroquine and chloroquine are two medications that have been used to treat malaria and autoimmune conditions like rheumatoid arthritis and lupus. Some studies suggest that both medicines may also help treat hospitalized patients with mild cases of COVID-19. In contrast, other studies showed that hydroxychloroquine did not make a difference. Based on what we now know, the risks of heart problems and other issues appear to outweigh the benefits relative to treating COVID-19. More comprehensive studies are needed to confirm whether these medications work in treating COVID-19.

Convalescent plasma

On March 24, 2020, the FDA issued an Emergency Investigational New Drug (eIND) for convalescent plasma to treat people with COVID-19. Plasma is the liquid part of blood that carries blood cells. Currently, antibodies containing plasma from a recovered patient are given by transfusion to a patient suffering from COVID-19. The donor antibodies help the patient fight the illness, possibly reducing the length or lessening the severity of the disease.

In China, ten adults with severe COVID-19 symptoms were given convalescent plasma. The researchers reported that all symptoms (such as fever, cough, shortness of breath, and chest pain) had significantly improved within three days. Still, it is not widely available since healthcare centers have just recently begun collecting it.

Ventilators

Patients with increased respiratory complications, healthcare professionals are turning to ventilators to help patients breathe. Ventilators are used for patients that can no longer breathe and need the machine to help provide oxygenation. In short, a ventilator takes over the body’s breathing process when the disease has caused the lungs to fail. This gives the patient time to fight off the infection and time to recover. There are two types of medical ventilators that can be used to treat patients. 

Graphic showing two common types of medical ventilation

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How is the ventilator used? 

In severe cases, the virus can cause damage to the lungs, prompting the body’s oxygen levels to drop, making it harder to breathe. A ventilator pushes air with increased levels of oxygen into the lungs to alleviate these problems. The ventilator has a humidifier, adding heat and moisture to the air supply matching the patient’s body temperature.

Patients are given medication to stay sedated and help relax the respiratory muscles to tolerate the discomfort from the ventilators. 

Timeline of Ventilators

The average timeline of ventilators is two to three weeks, possibly even longer, when a COVID-19 patient requires mechanical ventilation support. Some individuals could require a tracheostomy, where a tube is inserted in the opening of one’s neck rather than down the windpipe. Doctors must consider whether a ventilator’s complications are worth it in giving the patient enough time to recover from COVID-19, which can take weeks on the machine.

Possible Complications 

The pressure from a ventilator can make a patient’s lungs collapse or increase the risk of pneumonia. Gradually, doctors use reduced volumes of oxygen with lower pressure to limit injury to patients. However, ventilators are still “not completely safe and harm-free,” says Dr. David Hill, a pulmonary and critical care physician and board member of the American Lung Association.

Rehabilitation

Rehabilitation usually involves physical and occupational therapy to help patients get up and to move again. Eventually, a patient will begin transitioning to either home or a rehabilitation facility to start the recovery process after being taken off the ventilator. The recovery process varies for each patient, and older individuals with existing medical conditions could have a longer recovery period

Though COVID-19 is still relatively new, researchers are still conducting studies such as clinical trials, to determine which treatment is effective for patients with mild to severe symptoms. 

Sources: 

  1. https://wordofhealth.com/2020/03/12/can-blood-plasma-be-used-to-treat-coronavirus/
  2. https://wordofhealth.com/2020/05/14/how-does-covid-19-affect-the-lungs/
  3. https://www.goodrx.com/blog/coronavirus-treatments-on-the-way/
  4. https://www.cidrap.umn.edu/news-perspective/2020/04/fda-warns-about-hydroxychloroquine-chloroquine-covid-19
  5. https://www.health.harvard.edu/diseases-and-conditions/treatments-for-covid-19
  6. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
  7. https://www.fda.gov/media/137565/download
  8. https://www.webmd.com/lung/news/20200415/ventilators-helping-or-harming-covid-19-patients#1
  9. https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma
  10. https://www.pnas.org/content/early/2020/04/02/2004168117
  11. https://www.bbc.com/news/health-52036948
  12. https://www.pbs.org/newshour/health/why-ventilators-are-increasingly-seen-as-a-final-measure-with-covid-19
  13. https://www.healthline.com/health/tracheostomy

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Covid-19

Orange County COVID-19 cases May 18

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Several North Orange Country cities continue to serve as the hotspot as coronavirus cases continue to increase in Orange County. For new cases, Anaheim, Santa Ana, Orange, and Buena Park produced half of all new cases from last week. 

A new update on Monday, May 18, 59 new cases were reported bringing the total in Orange County to 4,434, and 461 are from senior living residents and 350 from jail inmates. There were no new deaths reported Monday and the total number of deaths within the county remains at 88. Of the total deaths, 21 were people living in skilled nursing facilities.

With 24 of 25 hospitals reporting, there were 194 people in Orange County hospitalized due to the virus with 78 patients in intensive care units. On an average 1,595 people were tested each day, a reduction from 2,715 the previous week and 2,199 from the week before. Another 166 tests for the coronavirus were given on the last day, bringing the collective testing total to 80,533 in the county of 3.2 million people. For the county to reopen, the county is expected to report 1.5 tests per 1,000 residents each day.

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Sources: 

  1. https://www.ocbj.com/news/2020/may/18/covid-19-hotspots-oc/
  2. https://www.ocregister.com/2020/05/18/coronavirus-orange-county-reported-no-new-deaths-for-may-18/

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Coronavirus Antibody Testing is Coming to Orange County

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Orange County officials are working with UC Irvine to study how many people have been infected with COVID-19. Researchers will examine blood samples of 5,000 people for antibodies from COVID-19 to understand how many people have contracted the disease throughout the county. 

This month, samples that represent the county population will be examined, and eight to ten drive-through sites will be set up. Pin-prick tests will also be administered to collect blood and sent to UCI for an analysis of the blood samples.

Similar tests have already begun in Los Angeles, and Santa Clara counties, and the number of infections was more significant than the number of confirmed cases. Officials conducting the Orange County examinations expect to have the same result. 

Contrary to the testing administered in Los Angeles and Santa Clara, the UCI study is intended to be more extensive and rigorous by testing more individuals than the other two studies. Researchers will go to the homes of those who cannot go to the drive-through sites and try to reach under-served communities. These efforts will help to have better estimates of disease prevalence by age and race/ethnicity. To observe how subjects’ immune responses change, researchers will follow some subjects over time. 

The director and founding dean for UCI’s Program in Public Health Bernadette Boden-Albala is leading the effort with Tim-Allen Bruckner, an associate professor. The study costs about 1.5 million, the proposal says, and is the largest of three surveillance studies currently in the works at UCI. 

The LRW Group, who led the sample for Los Angeles study, has email, mobile, and land-line information for more than 800,000 adults in Orange County. The LRW Group will be charged with pulling together the sample of 5,000 people that represents the Orange County population. 

Researchers are in the process of finalizing, which finger-prick test to use, and hope to begin testing in the next couple of weeks. After data is collected, the results will be analyzed and aim to be ready for publication by fall. The study will consist of about 200 participants who have tested positive to COVID-19 or for antibodies. The participants will have blood drawn every two weeks over four months

This surveillance study will be sent to the County Board of Supervisors to inform how long to continue restrictive public health measures, identify who is at high risk for the disease, and understand the persistence of the duration of immunological responses

Sources:

  1. https://www.ocregister.com/2020/05/14/rigorous-coronavirus-antibody-testing-coming-to-o-c/
  2. https://wordofhealth.com/2020/05/11/cedars-sinai-expert-weighs-in-on-uncertainty-over-coronavirus-antibodies/

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