Bioprinting in Regenerative Medicine

Erna West, CELVI Founder and CEO

Three decades ago, almost no human cells could be grown and expanded outside the body. Today, advances in cellular biology mean that most cells can be grown in a laboratory and that organs can be reengineered. According to Dr. Atala, engineered organs such as skin, urethras, blood vessels, bladders and vaginas have been implanted in limited numbers in clinical trials.

“Several tissue-engineered products are advancing through the regulatory pathway so they can be eventually commercialized and disseminated widely. However, most of the engineered tissues now in the more advanced stages of the regulatory pathway were made by hand.”1 Tissue engineering by hand requires several steps, each with its own challenges.  It starts with sourcing a seed population of cells that includes tissue biopsy, cell culture and expansion.

The human liver contains about a 100 billion cells and is composed of many cell types, including hepatocytes, stellate cells and Kupffer cells.  When creating a liver, all the cell types need to be expanded at the same time in large numbers.  Care needs to be exercised to ensure that the resulting cells do not transform and remain functionally consistent with their intended use. The biomaterials are also complex.  They need to have the right properties to support cells in vitro but they also need properties which make them compatible and suitable for implantation into patients.

Adding the cells to the biomaterials with the interactions necessary to have the right environment for tissue formation in bioreactors and incubators adds another level of complexity to the process.

The field of 3D printing has advanced alongside the development of regenerative medicine. Bioprinting is the application of this technology in life sciences and medicine.  It is based on the same principle of assembling different materials into actual products.  The process of bioprinting can assemble cells, proteins and hydrogels into living structures.

“Although scientists in regenerative medicine initially had been constructing tissues manually to bring the technologies of the field to patients, it soon became obvious that the process needed to be automated, as the by-hand approach was arduous, time consuming, technically demanding, and expensive. Bioprinting had the potential to offer several advantages, such as reproducibility, precision, automation, scalability, and lower costs; features that could eventually allow the delivery of tissues on demand.”1

Bioprinting can construct anatomically and physiologically accurate 3D biological structures, but it is ready to advance the drug development process. Bioprinted tissue models such as liver or cardiac organoids fabricated with human cells may precede animal trials to test for efficacy and toxicity.

Bioprinted tissues can be interconnected (for example, the liver, heart and kidneys) to test drugs on a body-on-a-chip model before human clinical trials begin.  Such models may eventually reduce or eliminate animal trials.

Therapeutically, bioprinting will likely achieve clinical success first with the least complex tissues (such as skin) that are already being delivered, even if they are not yet shelf ready. “In the more distant future, with further progress in largescale cell culture, bioprocess engineering, and genetic strategies, it is possible that we will be able to design specific printable living structures that are not even conceivable today. Tissues printed with gene-edited cells from the diseased patient to achieve a normal endpoint or combination of extended bioprinted tissue units functionally interconnected similarly to that in the human body are examples that could lead to unforeseen progress in regenerative medicine.”1

“Bioprinting offers many promising opportunities. However, patience and perseverance are needed to realize the full potential of the technology.”1

Dr. Atala is the Editor‐in‐Chief of Stem Cells Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine, and the W. Boyce Professor and Chair of Urology at Wake Forest University.

Dr. Atala is a practicing surgeon and a researcher in the area of regenerative medicine. His work focuses on growing human cells, tissues and organs. Dr. Atala heads a team of over 450 physicians and researchers. Over twelve applications of technologies developed in Dr. Atala’s laboratory have been used clinically.

Dr. Forgacs is a physicist turned tissue engineer turned innovator and entrepreneur. He received his physics training at the Eötvös Loránd University, Budapest, Hungary. His academic affiliations include the George Vineyard Chair in Biophysics at the University of Missouri-Columbia and the Chanderna-Stirkey Chair in Theoretical Physics at Clarkson University, where he also served as the Director of the Shipley Innovation Center. He is the scientific founder of Organovo, Inc., Modern Meadow, Inc., and Fork & Goode, Inc., and serves as the Chief Scientific Officer of the latter. He is a pioneer in methods of building living structures, in particular by bioprinting. The technologies he has developed have been applied to drug development and testing and the engineering of biomaterials of animal origin, such as leather in an environmentally friendly and ethically conscious manner. Dr. Forgacs has been recognized by numerous awards. In particular, he is a member of the National Academy of Innovators and was named as one of the “100 most innovative people in business in 2010” by FastCompany.

References

  1. Anthony Atala, Gabor Forgacs.  Three-Dimensional Bioprinting in Regenerative Medicine: Reality, Hype, and Future. STEM CELLS TRANSLATIONAL MEDICINE 2019;8:744–745

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The treating doctor will determine the use of cord blood for treatment, depending on many factors, including the patient’s medical condition, the quality of the cord blood sample, if the patient’s own cord blood can be used or an adequately matched donor’s cord blood.The use of cord blood has been established in stem cell transplantation and has been used to treat more than 80 diseases. The use of cord blood in regenerative medicine is still being researched and there is no guarantee that treatments being studied in the laboratory, clinical trials, or other experimental treatments will be available in the future.The use of cord tissue stem cells is still in early research stages, and there is no guarantee that treatments using cord tissue stem cells will be available in the future. Cord tissue stem cells are found in the cord tissue which is stored whole. Additional processing will be required to isolate the stem cells from the tissue for use. CELVI (Pty) Ltd outsources all cord blood and tissue processing and storage activities to Next Biosciences in Midrand, South Africa, a licensed and AABB accredited facility.

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