Tissue Engineering & Regenerative Medicine

Thousands of people die every year waiting for an organ transplant and far more are plagued by diseased organs. Those with spinal cord injuries suffer from many other health issues as a result of their inability to move and walk. And while we marvel at the prowess of surgeons able to transplant a face or hand, the results are far from perfect.

Tissue engineering brings together several disciplines to create living tissue to replace or repair skin, a failing organ or a damaged or missing body part.

Jay Vacanti and Robert Langer are widely recognized as the pioneers of tissue engineering. Dr. Vacanti, the director of the Center for Regenerative Medicine at Massachusetts General Hospital, is also director of pediatric transplantation at MGH. After watching far too many children die waiting for liver transplants, he sought a way to grow liver tissue. So he teamed with the Langer Lab at MIT. By implanting a polymer scaffold seeded with liver cells into diseased rats, they can now get new liver tissue to grow and function within weeks.

Until recently, it seemed impossible to imagine that those with damaged spinal or vocal chords might someday walk or sing again. However, biomedical engineers simply see these as challenges to overcome.

Working with Dr. Vacanti, scientists at the Langer Lab snipped the spines of rats, rendering them paraplegic. They then used stem cells from other rats to grow the missing piece of spinal cord on polymer scaffolds. After receiving the engineered spinal cords, the paralyzed rats regained the ability to walk again, albeit with a slight limp.

Scaffolds

Cell cultures have long been grown in Petri dishes but these methods generate lumps of cells that cannot serve a functional purpose in the human body. Scaffolds provide both form and support for growing tissue. These scaffolds—made from biocompatible, biodegradable polymers—must accommodate and direct the spatial orientation of particular cell types.

This method is relatively easy if we simply want to generate cartilage, which does not require vasculature. But if we hope to someday generate “replacement parts”, we need to be able to create complex, naturally-occurring structures that possess multiple cell types and can supply itself with nutrients.

To construct a scaffold that can support a fully-functional 3D cellular matrix, bionanotechnologies are employed. Individual, 2D sheets are constructed and layered to mimic the interplay of an organ and
its vasculature.

Seeding

The scaffolds are then seeded with cells that have been growing in Petri dishes. These cells can be harvested from either a stem cell line or a donor—ideally the recipient of the transplant. The cell-scaffold construct is then bathed in a medium that encourages the cells to grow and multiply. As the cells multiply, they begin to acquire the shape of the scaffold, which eventually breaks down and is absorbed by the tissue.

Stem Cells

Adult stem cells can be derived from several types of cells, including blood, bone, muscle, skin, brain and liver cells as well as hair follicles. But isolating and cultivating them is difficult. And it is not clear whether adult stem cells can truly differentiate. Embryonic stem cells, on the other hand, can differentiate even while on the scaffolds. But any cells that have not yet differentiated at the time of transplantation could go on to form tumors.

Rejection

Some tissue types are grown in the lab prior to implantation while others require help from the body in order to thrive. And once the tissue has been implanted, there is always the concern about rejection. The Langer Lab is also working to provide a means for delivering immunosuppressants in a timed-release fashion, targeted only to the site of the transplant in order to avoid immunocompromising a patient.

Challenges

In addition to providing a blood supply, getting stem cells to properly differentiate and avoiding rejection, there are several other challenges that must be addressed. Providing a blood supply means seeding the scaffold with multiple cell types—and not all of those cell types grow at the same rate. Vascular tissues tend to be slower growing and so they must be prefabricated within the overall scaffolding. And the final product needs to look and function the way nature intended. There is also the issue of getting approvals for use in humans.

Real World Applications

In addition to replacing missing or damaged organs and tissues, engineered tissues could also be used to help test the effects of drugs. And some cosmetic surgeons are watching developments in tissue engineering with an eye towards advancing the potential of reconstructive surgery.

Researchers have already created tissues from all sorts of organs. Using engineering principles, we may soon see living flesh that looks just like the real thing—because it is the real thing.

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