Organ donation still represents a major problem worldwide and, only in the United States, approximately 17 people die everyday waiting for a lifesaving organ transplant. In 2019, 39,718 transplants were performed in the U.S., but the number of people that remain in the line is still enormous: on September 2020, more than 109,000 men, women, and children were on the U.S. national transplant waiting list [1]. The use of artificially grown human organs can be considered as an effective path to solving this organ shortage, mainly after the increasing advances in 3D bioprinting technology, which made it possible to build living tissue constructs in the shape of human organs in an easy and rapid manner. Anyhow, achieving totally functional artificial human organs using 3D printed tissues is not yet completely possible. There is a lack of appropriate cellular density and organ-level functions that are required for these constructs to be used in organ repair and replacement [2].
Methods that seek to improve 3D bioprinting techniques are constantly being developed to create an ideal and precise environment for the manufacture of artificial organs. At Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS), scientists have developed a technique named as SWIFT (sacrificial writing into functional tissue), that allows the 3D printing of vascular channels into living matrices composed of stem-cell-derived organ building blocks (OBBs) [3]. The SWIFT method enables the achievement of a high cellular density and a perfusable network that mimic blood vessels, both crucial aspects to be considered when designing a living construct aimed at replacing a human organ.
Figure 1: A branching network of channels of gelatin-based ink (red) is 3D printed into a living cardiac tissue construct composed of millions of cells (yellow) using a thin nozzle to mimic organ vasculature [5].
The SWIFT method works from creating hundreds of thousands of induced pluripotent stem cells (iPSC)-derived OBBs in the form of EBs (embryoid bodies), organoids, or multicellular spheroids, by growing iPSCs in adherent culture and transferring them into large-scale microwell arrays. After this process, the OBBs are placed into a mold and compacted via centrifugation to form a living OBB matrix, which is very viscous at temperatures around 4 oC, allowing the deposit of a sacrificial gelatin-based ink within it via embedded 3D printing, without damaging any cells. When the tissue construct is heated to 37°C, the OBB matrix stiffens and the sacrificial gelatin-based ink melts away, leaving behind a network of tubular channels embedded within the tissue construct. It was demonstrated that these bulk vascularized tissues mature and remain functional when perfused over long durations [4]. To analyze the efficacy of the method, organ-specific tissues that were printed with embedded vascular channels via SWIFT were compared with tissues grown without these channels. Contrary to what was observed for SWIFT-derived constructs, the cells present in the core of the tissues without tubular network were dead within 12 hours. The researchers also printed channels with a branched architecture within a matrix consisting of heart-derived cells and perfused media through these channels for over one week to analyze if the tissue was able to display organ-specific functions. During that time, the cardiac OBBs were able to mimic key features of a human heart by fusing together to form a more solid cardiac tissue, and its contractions became even more synchronous and over 20 times stronger than they were before. The SWIFT technique illustrates how 3D bioprinting can achieve high resolution and fidelity to mimic more structurally and functionally complex tissues. This method opens doors to creating, in a more enhanced way, personalized organ-specific tissues with embedded vascular channels for regenerative and therapeutic applications.[4, 5].
Figure 2: Comparison between organ-specific tissues that were printed with embedded vascular channels using SWIFT (right) and tissues grown without these channels (left) [5].
REFERENCES
1- Organ Donation Statistics. Organdonor.gov. 2020
2- Lindsay Brownell. A swifter way towards 3D-printed organs. Wyss Institute. 2019.
3- Cartola V. Harvard researchers develop new technique to create human organs. 3D Natives. 2019
4- Skylar-Scott M A, Uzel S G M, Nam L L, Ahrens J H, Truby R L, Damaraju S and Lewis J A Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci. Adv. 2019; 5: eaaw2459
5- Uijung Yong et al. Interdisciplinary approaches to advanced cardiovascular tissue engineering: ECM-based biomaterials, 3D bioprinting, and its assessment. Prog. Biomed. Eng. 2020; 2: 042003