3D Printing with Stem Cells Could Lead to Printable Organs

3D-printed organs are constructed using bio-ink, typically consisting of cultured cells paired with biopolymer hydrogels. The process involves harvesting stem cells from the patient and differentiating them into specialized cells for specific organs. A 3D-printed external ear was successfully implanted in a patient, demonstrating the potential of this technology in reconstructive surgery. It is possible that at some point in the future a 3D-printing process using human stem cells could print entire major organs from a patient’s own cells. When that future arrives, if you need a kidney transplant, you may get a 3D-printed organ created just for you. If scientists are able to achieve that milestone, they may look back fondly at a breakthrough printing process pioneered by researchers at Heriot-Watt University in Scotland in collaboration with Roslin Cellab, a stem cell technology company[4].

3D Printed Ears

3D printed ears represent a significant advancement in reconstructive surgery, offering new possibilities for patients with ear deformities or those who have lost an ear due to injury or disease. Imaging and Design: Surgeons use 3D CT scans of the patient’s unaffected ear (if available) to create a mirrored digital model. This model is then refined using specialized software to ensure it matches the patient’s anatomy. Material Selection: The ears can be printed using various materials, including: Biocompatible polymers like polycaprolactone (PCL) and/or living tissue made from the patient’s own cartilage cells. In some cases, the patient’s own cartilage cells are grown in a lab and then used to populate the 3D printed scaffold. In 2022, a significant milestone was reached when a surgeon successfully implanted a 3D printed outer ear developed in a laboratory. This procedure involved a 20-year-old woman born with a small and misshapen right ear, who received an implant made from her own cells[10].

Bioengineered Organs

Some simpler bioengineered organs exist, although they are not 3D printed. In 2006, Atala and his team announced the first successful bioengineered organ transplant[2], a bladder, which had been implanted into seven patients in 1999. Earlier this year he announced[3] the successful follow-up of four women given bioengineered vaginas in 2005-2008. [1]

As of 2018 doctors had successfully grown and transplanted perhaps only three organs that we’d heard about in the news: a bladder, a windpipe and some vaginas. Tissue engineered hearts[5] and lungs[6] may be still at the laboratory stage, but replacement vaginas made from the patient’s own cells have been around for a while. A paper in the Lancet confirms they continue to work years after surgery[9].

Four patients in a study had Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, which affects women who are genetically and hormonally normal but have an absent or greatly shortened vagina. MRKH may also produce a missing or defective cervix and uterus. Sex is usually painful for women with the condition and more than half a million are affected worldwide.

While we are some way from being able to enable most women with MRKH to conceive, the Wake Forest School of Medicine created sheets from biodegradable scaffolds and epithelial and muscle cells of four girls aged 13-18 with MRKH. Each vagina was shaped by the Federico Gomez Children’s Hospital, Mexico, to best match the body of the woman it was for. Follow-ups over the next 6-8 years using physical examination, tissue biopsies and MRIs indicated that blood vessels had connected to the implant and within months new cells formed spontaneously while the scaffold was slowly absorbed. A tri-layered structure remained in place after the scaffolding was gone and no abnormalities were observed.  The women responded to a questionnaire with responses in the normal range in regard to arousal, lubrication, orgasm and painless intercourse. Most significantly, the patients reported high satisfaction with the replacement vaginas[8].

A Bioengineered Windpipe

Another organ that has been bioengineered is a human windpipe. Doctors have given a woman a new windpipe with tissue grown from her own stem cells, eliminating the need for anti-rejection drugs.

“This technique has great promise,” said Dr. Eric Genden, who did a similar transplant in 2005 at Mount Sinai Hospital in New York. That operation used both donor and recipient tissue. Only a handful of windpipe, or trachea, transplants have ever been done[7].

3D Printing a Human Kidney, What are the Obstacles?

The 3D printing of functional human kidneys faces several significant obstacles:

Complex Microarchitecture – Kidneys have an intricate internal structure that is challenging to replicate:

• The kidney contains extremely detailed, tiny structures that allow it to filter waste from blood and produce urine[12].
• Current 3D bioprinting technology lacks the resolution to recreate the complex microarchitecture and multiple cell types found in kidneys[11].

The development of advanced bioprinting techniques like microfluidic bioprinting offers hope for recreating the kidney’s intricate structures. This method allows for co-extrusion in a core-shell format, enabling the production of filaments with diameters as small as 50 μm while maintaining high cell viability. As resolution and precision continue to improve, replicating the kidney’s complex microarchitecture may become feasible[19].

Cell Sources and Viability – Finding and maintaining appropriate cells is problematic:

• Identifying suitable and sustainable cell sources to construct kidney components remains difficult[11].
• Maintaining cell phenotype and viability during and after the lengthy manufacturing process is challenging[11].

Advances in pluripotent stem cell-derived renal progenitors show great promise for addressing cell source issues. These cells have contributed to the creation of in vivo-like rudiment structures with multiple renal cell types[19]. Additionally, the development of specialized bioreactors and improved cell culture techniques may help maintain cell phenotype and viability during and after the manufacturing process.

Vascularization – Creating the necessary blood vessel networks is a major hurdle:

• Even the most advanced 3D printers cannot yet print the tiny networks of blood vessels required to keep full-scale organs healthy[12].
• Without proper vascularization, 3D printed tissues cannot receive adequate oxygen and nutrients to survive.

Recent breakthroughs in creating vascular networks offer hope for overcoming this challenge. In 2021, two teams from the Wake Forest Institute of Regenerative Medicine successfully met NASA’s challenge to create a working vascular system[20]. As this technology advances, it may soon be possible to print the complex vasculature needed for full-scale kidney function.

Scaling and Functionality – Moving from small models to full-size functional organs is extremely difficult:

• While simplified miniature kidney models have been created, scaling up to full-size functional organs remains out of reach[12].
• Reproducing the kidney’s complex filtration and regulatory functions in a printed organ is still not possible with current technology[11].

While scaling up remains challenging, progress in bioprinting larger structures is ongoing. Companies like Vital3D are focusing on developing fast and precise 3D bioprinting systems specifically for larger organs like kidneys[20]. As these technologies mature, the gap between miniature models and full-size functional organs may narrow.

Manufacturing and Clinical Translation – Practical and regulatory challenges exist:

• Developing reliable, scalable, and timely manufacturing processes for clinical use is imperative but not yet achieved[11].
• Identifying clinical pathways for translating experimental models to human use presents significant hurdles[11].

Experts estimate that fully functional 3D printed kidneys suitable for transplantation are likely still a decade or more away from becoming a reality[2]. Current research is focused on creating simpler kidney tissue models for drug testing and disease modeling as intermediate steps toward the ultimate goal of printable replacement organs.

Bioartificial Kidney Research

For now, Scientists at UC San Francisco are working on a bioartificial kidney device that could potentially free patients from dialysis1. This implantable device, called a bioreactor, contains living kidney cells and is designed to mimic several important kidney functions[21].

Stay tuned for the future of 3d printable stem cell created human organs.

Read More