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Urinary bladder bioprinting for fully autologous transplantation

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Treating bladder conditions could be as easy as pushing print

By laser-printing bladder tissue, researchers hope to alleviate – if not eliminate – the many side effects associated with cystoplasty and orthotopic neobladder surgery.

Trauma, cancer, inflammation, incontinence and a host of other conditions can all require bladder augmentation. Also called cystoplasty, this surgical procedure enlarges the bladder by patching it up, typically using pieces of the patient’s own intestine or stomach. While the procedure does improve urine storage, reduce leakage and, in the case of cystectomy patients, divert urine, these advantages come with some long-term risks. “Because intestinal and bladder tissues aren’t fully compatible, most patients experience a range of complications that can have a serious impact on their quality of life,” says Apostolos Klinakis, a researcher at the Biomedical Research Foundation of the Academy of Athens(opens in new window). These complications have fuelled an effort to develop engineered bladder tissue – an effort that received a big boost with the advent of 3D printing technology. “By enabling the printing of living cells, 3D printing represents a new era for regenerative medicine,” adds Klinakis. However, the technology is typically used to print simple tissues, such as cornea tissue in the eye, and not complex tissues such as those found in the bladder. But with the support of the EU-funded UroPrint(opens in new window) project, Klinakis and an interdisciplinary team of highly skilled researchers intend to change that. “Our goal was to laser-print fully functional, immunocompatible urothelial tissue both ex and in vivo for use in bladder augmentation and replacement,” explains Klinakis.

Innovative bioinks and laser printing system

To make this vision a reality, the project made a number of important advancements in such fields as optics, laser technologies, material sciences, engineering, micro-instrumentation and experimental surgery. Amongst these achievements are protocols for the development of smooth muscle and urothelial cells derived from primary human bladder biopsies, along with their expansion and cryopreservation in accordance with good manufacturing practices. The project also developed hydrogel bioink formulations based on a biomaterial derived from human platelet lysate methacrylated (PLMA). Other key deliverables include a device that measures the physio-mechanical and permeability properties of the printed grafts, as well as hardware and processes that allow for the efficient printing of cells. “Despite such challenges as a scarcity of bioptic material and difficulty expanding urothelial cells from old-age biopsies, the project succeeded at developing innovative bioinks and a laser printing system that allows for the adjustment of printing parameters based on anatomic variabilities,” notes Klinakis.

An effective way of treating bladder conditions

According to Klinakis, by enabling the laser bioprinting of bladder tissue, the project addresses a long-standing challenge to effectively treating bladder conditions. “By alleviating or even eliminating those side effects associated with grafting intestine and bladder tissue, we not only improve the quality of life for patients and family, but because laser-printed tissue is more cost-effective, we also reduce their financial burden,” he concludes. Project researchers are now working to publish their results in scientific journals and move their laser printing solution towards human trials. They are also exploring how it can be used in other areas of regenerative medicine.

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