3D Printed Tissues From Bench to Bedside
3D bioprinting has the potential to provide significant medical advances. For example, 3D printing of functional tissues and organs could someday alleviate shortages in organ availability and the problem of organ incompatibility. But where does the field stand today?
A look at the research benches of top labs can give us an idea. In this post we’ll take a look at CELLINK’s innovative inks and printers, ORGANOVO’s functional bioprinted tissues, Dr. Anthony Atala’s Wake Forest Institute for Regenerative Medicine, and the 3D printed cortical fibers line by Xtant Medical, 3Demin®.
CELLINK is the world’s first bioink company. A Swedish company founded in 2016, CELLINK solved problems for the tissue engineering community by commercializing hydrogel bioinks which can be used to 3D print cartilage, bone, skin, or muscle. CELLINK is also a top provider of bioprinters. It’s likely to be one of CELLINK’s printers in a researcher’s lab being used to create 3D printed allografts during experiments, as was the case of the 3D printed cartilage mentioned in the prior post. With the right raw materials, it’s possible to create multiple biologics scaffolds and structures, and CELLINK is at the forefront of bioink development.1
ORGANOVO creates functional, responsive bioprinted human tissue models for preclinical testing and drug discovery research. Their 3D bioprinted tissues remain viable and dynamic for more than 28 days in vitro.2 Their key architectural and functional features mimic natural function and provide important information for scientists.
Pharmaceutical companies conducting research can examine the effects of new compounds on ORGANOVO’s ExVive™ 3D bioprinted human tissues. This allows tissue-specific data to be collected to better predict human outcomes, lower total development time, and reduce costs.
For example, liver and kidney tissues can be used to evaluate drug exposure for both acute and chronic toxicity and metabolism studies.2 ORGANOVO is also working on developing functional, 3D tissues for implantation or delivery into the human body, with the intention of creating these tissue for use for repair or replacement of damaged or diseased tissues.3
The Wake Forest Institute for Regenerative Medicine is one of the nation’s top research labs working to translate scientific discoveries in 3D printing into clinical therapies. Led by Dr. Anthony Atala, a pioneer in medical tissue engineering, this interdisciplinary team is engineering more than 30 different replacement tissues and organs to develop curative cell therapies.4 Wake Forest was the first institution to successfully engineer laboratory-grown organs and implant them into humans: these were engineered bladders grown from the patient’s own cells.5
The fact is, all living tissues are composed of many different cell types arranged in a specific order that is essential to function. Therefore, when using 3D printing to create a tissue, precision is critical.6 Researchers at Wake Forest have designed their own inkjet bioprinter that can print kidney cells, and the binders to hold the cells together, into a 3D kidney prototype. This bioprinter could potentially be used to create a custom organ based on a CT scan and patient data. Their bioprinter is also being tested in the creation of other structured tissue, such as the ear.7
While 3D bioprinting of living, functional, clinically applicable tissues and organs remains the Holy Grail, there are much simpler examples of the technology already commercialized and in use today. Bacterin’s 3Demin® line of demineralized cortical bone fibers is bioprinted into different shapes and sizes designed for specific surgical applications. The bioprinting process creates a porous, interconnected allograft that contains BMPs and other growth factors necessary to promote new bone formation. It is an osteoconductive demineralized cortical fiber matrix with osteoinductive potential that can be used as a stand-alone graft, or in combination with autologous bone, bone marrow, DBM putty, and other products.8
Bacterin’s production of customized bone implants using 3D printing technology was applied clinically during a mission sponsored by the World Craniofacial Foundation. In Zambia, a child named Grace Kabelenga was born with the most severe facial cleft in 40 years (Tessier 0-14), and a total absence of the bones separating her brain from her oral cavity.9 3D printed plastic prototypes allowed the team to simulate surgery and to create molds for custom bone implants. Bacterin’s 3Demin® bone allograft material was used to create custom 3D printed bone to serve as a “bandeau” to define the superior orbital rims above her eyes.10 This was combined with other Bacterin allografts and rhBMP2 to reconstruct missing parts of Grace’s skull.
Multiple surgeries have allowed Grace to function as a normal child would. Allografts.com members can view a video about the WCF mission on our portal. A slide deck is also available here.
3D printing for tissue engineering has the potential to provide incredible benefits to humankind if the technology can be developed to its full potential for medical applications.
If you missed it, you can read more about the history and applications of bioprinting here: 3D Printing in Tissue Engineering.
References:
1 CELLINK. (2017). BioX Printer. Retrieved from https://cellink.com/bioprinter/
2 ORGANOVO. (2017). 3D human liver tissue testing services. Retrieved from http://organovo.com/tissues-services/exvive3d-human-tissue-models-services-research/3d-human-liver-tissue-testing-services/
3 ORGANOVO. (2017). About ORGANOVO. Retrieved from http://organovo.com/about/about-organovo/
4 Wake Forest School of Medicine. (n.d.). Wake Forest Institute for Regenerative Medicine. Retrieved from http://www.wakehealth.edu/WFIRM/
5 Wake Forest Baptist Medical Center. (2006). Wake Forest physician reports first human recipients of laboratory-grown organs. Retrieved from http://www.wakehealth.edu/News-Releases/2006/Wake_Forest_Physician_Reports_First_Human_Recipients_of_Laboratory-Grown_Organs.htm
6 Wake Forest School of Medicine. (2017, September 6). Using 3D printing technology to print organs and tissue. Retrieved from http://www.wakehealth.edu/Research/WFIRM/Our-Story/Inside-the-Lab/Bioprinting.htm
7 Wake Forest School of Medicine. (2016, August 8). Replacement organs and tissues: Engineering a kidney. Retrieved from http://www.wakehealth.edu/Research/WFIRM/Research/Engineering-A-Kidney.htm
8 Bacterin. (2015). 3Demin Benefits. Retrieved from: https://xtantmedical.com/app/uploads/2016/09/3Demin_Brochure_Digital-14009B.pdf
9 3D Systems. (2016). Delivering the gift of a normal life. Retrieved from: https://www.3dsystems.com/sites/default/files/2016/cs_3ds_grace_kabelenga_0316_0.pdf
10 3D Systems. (2017). Delivering the gift of a normal life with 3D systems healthcare solutions. Retrieved from 3D Systems. Delivering the gift of a normal life with 3D systems healthcare solutions. Retrieved from https://www.3dsystems.com/learning-center/case-studies/delivering-gift-normal-life
