Researchers Quantify Tissue Networks at McGowan Institute.

Dr. William Wagner (left), director of the McGowan Institute for Regenerative Medicine, reviews scanning electron microscope images of synthetic tissue scaffolds with researcher Antonio D’Amore.

By Tom Imerito

At their weekly meeting, Doctors William Wagner and Antonio D’Amore are reviewing progress on D’Amore’s efforts to transform images of biological tissue into mathematical data.

D’Amore’s work will be instrumental in engineering synthetic materials for implantation in patients suffering from tissue and organ insufficiencies.   For Wagner, who was named director of the McGowan Institute for Regenerative Medicine earlier this year, meeting with D’Amore is just one of a multitude of administrative tasks associated with managing the Institute as well as serving as lead investigator for his own group of a dozen-or-so researchers.

D’Amore shows his boss a skeleton-like map of a tissue fiber network detailing each fiber segment’s size, shape, position, angle, intersections, and overlaps along with their corresponding mathematical values.  He has produced the map by running a scanning electron microscope image through software filters he has developed.  The process is not only more accurate than human measurement – at three minutes per image it is forty times faster than the two hours of manpower it took previously.

D’Amore’s innovation comes at a perfect time.  Recently the focus of tissue engineering has shifted toward smaller components of the tissue generation mechanism, including D’Amore’s area of interest – the mechanical properties of the non-cellular collagen scaffolds, called extracellular matrices – into which cells implant themselves and multiply to form organs.

A native of Palermo, Italy, with a PhD in biomechanics and tissue engineering, D’Amore is also a fellow of The Ri.MED Foundation, an international partnership between the Italian Government, the Region of Sicily, the University of Pittsburgh, and UPMC.  He gravitated to McGowan as a result of its renown as a Mecca for regenerative medicine.  Similarly, twenty years earlier Wagner had gravitated to Pittsburgh for precisely the same reason.  UPMC and its academic partner, the University of Pittsburgh, had, and still has, all the essential ingredients for the continuously emerging field – transplant surgeons, medical specialists, research scientists, and engineers of every ilk – all of which attract an abundance of patients.  The only missing ingredient was, and continues to be, a sufficient supply of donor organs, which serves as the driving force behind McGowan’s three-pillar, patient-centric approach to the problem of replacing failed tissues and organs.

The first of the pillars is made up of intermediary assistive devices, such as heart pumps and artificial lungs, which are designed to keep patients alive while they wait for donor organs.  Next, the field of tissue engineering – D’Amore’s area of expertise – attempts to remedy tissue and organ deficiencies with both natural and synthetic substitutes.  Finally, stem cell therapy has emerged as a viable option due to the discovery of ways to coax adult stem cells to differentiate into a variety of organ cells.  But, rather than looking for ideal solutions for any one of these areas at some point in the future, McGowan mixes and matches all of them to improve the lives of individual patients today.

Click to expand

Scanning electron microscope images of biological extracellular matrix tissue scaffolds and synthetic electrospun polyester urethane urea tissue scaffolds.
Top: Fiber network and diameters detected by the algorithm, A) isotropic elastomeric scaffold, B) anisotropic elastomeric scaffold. Fiber network and diameters manually detected, C) isotropic elastomeric scaffold, D) anisotropic elastomeric scaffold.
Bottom: Detected fiber networks for A) isotropic elastomeric scaffold, B) anisotropic elastomeric scaffold, C) Rabbit MSC seeded collagen gel, D) Decellularized rat carotid arteries. (Click image for full size)

This eclectic, solution-focused approach is exemplified in an epiphany D’Amore had when he first arrived in Pittsburgh last year.   An astute amateur photographer, D’Amore was photographing a tree next to Pitt’s Cathedral of Learning when an unexpected connection between the structure of the tree and that of the fiber networks he was studying at work occurred to him.  While observing the tree’s branches against the sky, D’Amore realized that he was mentally defining the tree’s geometry by successively identifying the boundaries, intersections, sizes and directions of its branches.  It struck him that, using the same method his brain naturally used to define the tree, he could write a computer program to mathematically map tissue fiber networks much faster than any human could.  It wasn’t long before D’Amore’s work was published in the field’s leading journal, Biomaterials.

In an amazing feat of mathematical gymnastics, D’Amore extracts digital values from analog microscope images of biological tissue and converts them into computer control input values for a synthetic tissue scaffold fabrication system.  The fabrication process entails precisely depositing electrically atomized strands of a synthetic plastic called polyester urethane urea on a spinning cylinder at varying angles and directions to simulate the forms and performance characteristics of living tissue networks.  The resulting ES-PEUU scaffold (electrospun polyester urethane urea) can be seeded with stem cells during manufacture, ready for implantation and growth in a biological system.  Once inside a body the stem cells divide and populate the scaffold to produce new functioning organ tissue.  When the cells fully populate the scaffold, the synthetic material is absorbed by the body and eliminated.

Although the process is promising, it is still in the laboratory.  And although D’Amore’s innovation represents progress, the field of tissue engineering is still fraught with many more questions than answers.  But in the quest to improve human lives, nobody is looking more intently for solutions than Drs. Wagner, D’Amore and their colleagues at the McGowan Institute for Regenerative Medicine.

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Tom Imerito is president of Science Communications, a Pittsburgh technology public relations consultancy.  He can be reached at 412-892-9640 or thomas@science-communications.com.  To learn more about Science Communications, please visit www.science-communications.com

An abridged version of this article first ran in TEQ magazine. You can read it here: