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Anthony Atala, senior author of this study, is one of the foremost leaders in Regenerative Medicine. Over the past decade and a half he’s assembled a world class multi-disciplinary team of stem cell biologists, tissue engineers, transplant surgeons at Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina. One of Atala’s major claims to fame came in 2006 with the transplants of in vitro grown fully functional autologous urinary bladders into 7 human recipients (1). All this to say the study’s provenance is solid, the approach pioneering, indeed a major technological advance.

Thus far, tissue and organ engineering followed a more cumbersome play book. Seed cells onto acellular bio-mechanical scaffolds and grow in vitro. The technical advances in Atala et al‘s ITOP (Integrated tissue-organ printer) approach are several

  • Use CT and MRI to build a detailed 3-D construct of the tissue so blueprint is much closer to living reality.
  • Incorporate lattice of micro-channels throughout the construct to allow oxygen and nutrients to permeate throughout the structure to sustain cell viability.
  • Apply scaffold and cells together, i.e., build the entire tissue piece at once. No need for long-term culture.
  • Doing so they successfully 3-D printed complex tissue such as bone and cartilage. Even more remarkably, they managed to create in situ soft tissue like skeletal muscle. Then they implanted
    • Rat calavarial bone constructs into 4 Sprague Dawley (immune-replete) rats and examined their health and viability 5 months later.
    • Rabbit ear cartilage constructs onto 4 athymic (immune-deficient) mice and examined their health and viability 1 and 2 months later.
    • Mouse skeletal muscle into 6 athymic nude rats and assessed its function 2 weeks later.

In vitro tissue printing has the potential to reinvigorate transplantation. Surgical innovations and rapid development of a transplant ecosystem have made previously unimagined tissue and organ transplants possible. However, transplantation’s promise remains unfulfilled as acute organ shortages mean that more people die on waiting lists compared to those lucky enough to get transplants. The promise and hope of being able to print living tissue lies in reversing that balance. In essence then this study is early proof of concept and it fulfills the terms of such a test well.

However, reality knocks on the door to remind that medical applications of living tissue printing in humans may be several years from fruition.

  • The tests in this study were of tiny pieces of tissue implanted into small numbers of animals.
  • Of the 3 tests, the rat bone construct implanted into rats (homologous) with intact immune systems was the only real-world test. What’s not clear from the paper is whether all 4 rats with the bone transplant tolerated their grafts.
  • Ear cartilage and skeletal muscle transplants being done cross-species on animals without a thymus, i.e., without a fully functioning immune system, not clear if normal bodies would tolerate such constructs. And this is a really big question.
  • One way of minimizing this question or even making it disappear altogether would be to take patient’s own cells (autologous) and seed them into ITOP to construct the tissue. Would such cells need to be cultured first? Primary cells are notoriously difficult to culture. Would stem cells work better? Are stem cells readily available for different tissues and organs, especially from patients with a variety of disease conditions that necessitate transplants in the first place? These are just some of the difficult questions that need answering first.
  • Could such tissues ever be implanted directly into humans without undergoing rigorous tests for toxicity and safety first?
  • The other challenge is to increase the complexity. Is it possible to in vitro print entire organs? After all, the major transplant waiting lists are for solid organs such as heart, kidney, liver, lung, pancreas, etc.
  • Thus, until these efforts are repeated, their scope expanded and shown to work for humans, this study will remain an early proof of concept, much like Atala’s 10-year old study of in vitro grown fully functional urinary bladder transplants which never became mainstream.


1. Atala, Anthony, et al. “Tissue-engineered autologous bladders for patients needing cystoplasty.” The lancet 367.9518 (2006): 1241-1246. http://www.zo.utexas.edu/courses…