Design and Usability Evaluations of a 3D‐Printed Implantable Drug Delivery Device for Acute Liver Failure in Preclinical Settings

Abstract

Acute liver failure (ALF) requiring liver transplantation is a disease that occurs due to rapid hepatocellular dysfunction. As liver transplantation has various limitations, including donor scarcity, high cost, and immuno-incompatibility, continuous local delivery of biopharmaceuticals to the liver tissue can be a promising ALF treatment option. Here, the in vivo safety and usability of a 3D-printed implantable drug delivery device for effective ALF treatment is evaluated. The implantable reservoir consists of a 3D-printed container and a semipermeable membrane for repeated administrations of drugs, specifically to the liver tissue. The physical stability and function of the 3D-printed reservoir are confirmed by the mechanical properties and in vitro drug release test, respectively. In mice implanted with the reservoir system, mortality, weight changes, clinical signs, hematological and serum biochemical changes, and organ weight changes are not observed, suggesting no foreign body reaction. The usability of the reservoir system is further evaluated using an ALF model of 70% hepatectomized mice treated with N-acetylcysteine through the system, showing cell-specific regeneration and significant liver injury alleviation. Overall, the 3D-printed reservoir system is safe for studying the therapeutic potential of ALF treatment, and it can be used for the delivery of various active pharmaceutical ingredients.

Connected healthcare: Improving patient care using digital health technologies

“…3D printing has also been utilised for the production of personalised drug-eluting implants and medical devices [172][173][174][175]. For example, researchers have combined the use of scanners with 3D printing in order to create drug-eluting anti-acne masks, anatomically tailored wound dressings, mouthguards, and bespoke anti-biofilm multi drug-loaded hearing aids [128,[176][177][178].…”

Applications, advancements, and challenges of 3D bioprinting in organ transplantation

“…Owing to its complex structure and function, the reconstruction of the liver is a major problem in the application of 3D printing technology in the field of organ transplantation. 109 In order to overcome these obstacles, various liver-on-a-chip models have been approved for in vitro liver drug testing. 110 With the help of bioprinting, Lee et al developed a three-dimensional liver-on-a-chip model, including different types of liver cells, liver ECM microenvironments, and vascular/biliary fluid tubes.…”

Three Dimensional Bioprinting for Hepatic Tissue Engineering: From In Vitro Models to Clinical Applications

“…The container in the reservoir was 3D printed which contains a semi-permeable membrane for administration of drugs. The study concluded that the system was safe for acute liver failure treatment and that various drugs could be administered via this 3D printed device [ 273 ]. Organ-on chip devices have gained a lot of traction these days for in-vitro studies of pathophysiological processes for drug screening.…”