Clinical Bioprinting Is Coming of Age: Ex Vivo Versus In Vivo : Response to the Letter to the Editor

Dear Editor,

A letter to the editor ¹ responding to an article published in your journal ² suggested that there are still no clinically available options for bioengineered auricle products. In our opinion, this creates a misimpression among readers regarding the prospects of obtaining such products in the near future.

The year 2022 marked a milestone in clinical translation: regulatory approval (ID NCT04399239, USA) was granted for the clinical bioprinting of auricular cartilage to treat unilateral microtia.^3,4 Within these clinical trials, 3DBio Therapeutics and the Microtia-Congenital Ear Deformity Institute performed ear reconstructions on two patients using AuriNovo™—living tissue implants produced via bioprinting; to our knowledge, the printed constructs successfully matured into functional cartilage in these patients.

For clinical translation, the company created a technological platform for auricle production that meets FDA requirements for the manufacture of regenerative medicine products, including a new and patented 3D bioprinter, new bio-inks, a specialized cell culture system, and implantable protective shell technology. According to the company, the U.S. Food and Drug Administration assigned AuriNovo™ Orphan Drug and Rare Pediatric Disease designations.

Undoubtedly, the prospects for this field as a whole are very bright. Bioprinting is based on constructing a digital model of an organ and the robotic, high-precision reproduction of its form; it merges digital technologies with biology. The clinical translation of bioprinting technology has begun, the first review of the clinical translation of bioprinting has already been published. ⁵ The list of printed human tissues and organs includes cartilage, skin, blood vessels, nerve conduits, and the trachea.

At least five private companies in five different countries, including the USA, Japan, France, China, and South Korea, have begun bioprinting human tissues and organs.

ROKIT Healthcare (South Korea) uses bioprinting to treat diabetic foot ulcers. The ulcer healing rate is accelerated twofold.

Scientists at Kyoto University (Japan), using a bioprinter (Cyfuse^®) and the Kenzan method with tissue spheroids, printed a tissue-engineered tube (Bio 3D), which was used as a nerve conduit for the successful treatment of human nerve damage and regeneration.

Revotek Co., Ltd. (China) developed unique 3D-bioprinted personalized blood vessels.

In 2023, Seoul St. Mary’s Hospital (South Korea) performed a transplantation of a trachea created using 3D printing (with a bioprinter from T&R Biofab).

Poietis Biosystems was the first to print skin in France and began clinical trials of the bioprinted product Poieskin^® in Marseille for military medicine.

All the provided examples of created tissues and organs were printed ex vivo. We believe that in situ bioprinting can accelerate progress; this is a less costly and perhaps the most promising bioprinting method, as it does not require a perfusion bioreactor for construct maturation or expensive Good Manufacturing Practice-standard cleanrooms. The human body is more effective for maturation than modern laboratory bioreactors. The construct is assembled directly in the body intraoperatively and interacts with the recipient; complex transfer and potential damage during implantation of fragile printed constructs are excluded. Except for Russia, this bioprinting method has not yet been applied anywhere in the clinic.

Thus, the clinical translation of bioprinting is already underway worldwide. The concept of organ bioprinting was proposed more than 20 years ago, and today bioprinting in the clinic is already a reality. It is logical to expect further development of clinical bioprinting in the next decade. The remaining technical barriers are surmountable. Organ bioprinting will transform surgery and transplantation. Standardizing and scaling bioprinting methods is a necessary condition for the further progress of the clinical translation of bioprinting that has begun. Creating a registry of printed organs is the next logical step.