Researchers engineer natural windpipe replacement alternative to synthetic scaffolding now being used

February 14, 2018, Case Western Reserve University

Biomedical engineers at Case Western Reserve University are growing tracheas by coaxing cells to form three distinct tissue types after assembling them into a tube structure-without relying on scaffolding strategies currently being investigated by other groups.

Successful trials and further research and development could someday allow surgeons the option of replacing damaged or faulty trachea with a fully functional natural- trachea in both adults and children, said Eben Alsberg, professor in Biomedical Engineering and Orthopaedic Surgery and director of the Alsberg Stem Cell & Engineered Novel Therapeutics (ASCENT) Lab at Case Western Reserve University.

"The unique approach we are taking to this problem of trachea damage or loss is forming tissue modules using a patient's cells and assembling them like childhood toy Legos into a more complex tissue," said Alsberg, who is leading the research.

This step toward building living windpipe structures from self-assembled modules is explained in detail in the most recent issue of Advanced Science.

Co-authors include: Marsha Rolle, an associate professor of biomedical engineering from Worcester Polytechnic Institute in Worcester, Massachusetts; Hannah Strobel, a WPI graduate student; Calvin Cotton, a professor of pediatrics and physiology and biophysics at Case Western Reserve; and nine researchers from Alsberg's lab, including co-first authors Anna Dikina and Daniel Alt.

The research was supported by a $1.9 million grant from the National Institutes of Health's National Institute of Biomedical Imaging and Bioengineering.

The problem

The trachea, commonly called the windpipe, is the airway between the voice box and the lungs. Patients may need a rebuilt trachea because of tumor resection or an injury that results in tracheal stenosis, a narrowing or constricting of the windpipe, which inhibits breathing.

Damage to or loss of trachea tissue can be life-threatening or lead to a significantly reduced quality of life, Alsberg said.

Doctors have limited solutions for patients with damaged tracheas. If a portion of the trachea is damaged, for example, they can only surgically join the ends if less than half of the trachea is damaged in adults or less than 30 percent in children.

Other procedures, such as implanting a stent or simply clearing away tissue obstructing the airway, offer only short-term relief as the repaired tube tends to close off again after about a year.

Recent tissue-engineering approaches using synthetic or natural materials as scaffolding for cells have been met with challenges.

Difficulties have included uniformly seeding cells on the scaffolding, recreating the multiple different tissue types found in the native trachea, tailoring the scaffolding degradation rate to equal the rate of new tissue formation, and recreating important contacts between cells because of the intervening scaffold.

Improving upon current treatments

The trachea engineering strategy now being pursued at Case Western Reserve, however, wouldn't have those problems because it doesn't rely on a separate scaffold structure, Alsberg said.

According to Alsberg's research, a new trachea replacement must do three critical things to function properly:

  1. maintain rigidity to prevent airway collapse when the patient breathes;
  2. contain immunoprotective respiratory epithelium, the tissue lining the respiratory tract, which moistens and protects the airway and functions as a barrier to potential pathogens and foreign particles;
  3. and integrate with the host vasculature, or system of blood vessels, to support epithelium viability.

The self-assembling rings developed by the Alsberg and Rolle labs meet all three of those requirements because they can fuse together to form tubes of both cartilage and "prevascular" tissue types. Prevascular refers to tissues potentially ready to participate in the formation of blood vessels, though not yet functional in that way.

The cartilage rings are formed by aggregating marrow-derived-stem cells in ring-shaped wells. Polymer microspheres containing a protein that induces the stem cells to become "chondrocytes," or cells that form cartilage, are also incorporated into the cell aggregates.

Rolle said it is the combining of those two things-the self-assembled tissue ring modules and the polymer microspheres-that "makes it possible to create the complex multi-tissue structure that makes up the trachea."

The prevascular rings are comprised of both these marrow-derived stem cells and endothelial cells, the thin layer of cells that line the interior of blood vessels.

The researchers then coat the tubes with epithelial to form multi-tissue constructs that satisfy all of those requirements: cartilage provides rigidity, epithelium serves the role of immunoprotection and the vascular network would ultimately permit blood flow to feed and integrate the new trachea tissue.

Using this method, Alsberg, Rolle and their team have been able to engineer highly elastic "neo-tracheas" of various sizes, including tissues similar to human . When these tracheas were implanted under the skin in mice, there was evidence the prevascular structures could join up with the host vascular supply.

"The hope is that a surgeon could implant the tissue tube into the body and it will grow and incorporate into the existing tissue," Alsberg said. "We're excited about this approach, as it may have broad applicability to bottom-up engineering of many other complex tissues and organs."

Explore further: Scientists develop tissue-engineered model of human lung and trachea

More information: Anna D. Dikina et al, A Modular Strategy to Engineer Complex Tissues and Organs, Advanced Science (2018). DOI: 10.1002/advs.201700402

Related Stories

Scientists develop tissue-engineered model of human lung and trachea

November 11, 2016
Scientists at Children's Hospital Los Angeles have developed a tissue-engineered model of lung and trachea which contains the diverse cell types present in the human respiratory tract. The study, led by principal investigator ...

New molecular probes to allow non-destructive analysis of bioengineered cartilage

January 16, 2018
A new study describes novel probes that enable non-invasive, non-destructive, direct monitoring of the differentiation of mesenchymal stem cells (MSCs) in real-time during the formation of engineered cartilage to replace ...

Inhibiting TOR boosts regenerative potential of adult tissues

December 7, 2017
Adult stem cells replenish dying cells and regenerate damaged tissues throughout our lifetime. We lose many of those stem cells, along with their regenerative capacity, as we age. Working in flies and mice, researchers at ...

Leading surgeons warn against media hype about tracheal regeneration

March 25, 2014
Reports of the two earliest tissue-engineered whole organ transplants using a windpipe, or trachea, created using the patient's own stem cells, were hailed as a breakthrough for regenerative medicine and widely publicized ...

Engineering cartilage replacements

December 2, 2011
A lab discovery is a step toward implantable replacement cartilage, holding promise for knees, shoulders, ears and noses damaged by osteoarthritis, sports injuries and accidents.

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Anonym412392
not rated yet Feb 14, 2018
I have had emphysema for about five years. I was on oxygen during the day but not at night. I could go about two hours without the oxygen, and then I need it. I had a converter in the house and oxygen tanks for when I go shopping, etc. I am 64 years old and in relatively good health. The doctor said it was caused by a combination of smoking, dust here in Vegas, and 30 years of smog in California. I believed I will always need the oxygen to breathe. I quit smoking 15 years ago. But the damage has been done. January 2017 my pulmonologist and I decided to go with natural treatment and was introduced to Green House Herbal Clinic natural organic Emphysema Herbal formula, i had a total decline of symptoms with this Emphysema Herbal formula treatment. Visit Green House Herbal Clinic official web-site ww w. greenhouseherbalclinic. com. The infections, shortness of breath, fatigue, dry cough and other symptoms has subsided.  I am very pleased with this treatment. I breath very well now and e

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.