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Microgravity bioprinting is the utilization of 3D bioprinting techniques under microgravity conditions to fabricate highly complex, functional tissue and organ structures. [1] The zero gravity environment circumvents some of the current limitations of bioprinting on Earth including magnetic field disruption and biostructure retention during the printing process. [2] Microgravity bioprinting is one of the initial steps to advancing in space exploration and colonization while furthering the possibilities of regenerative medicine.
The main function microgravity bioprinting has over the other 3D bioprinting techniques is the utilization of a zero gravity environment. All other techniques of 3D bioprinting have been tested in space including extrusion-based printing, lithography-based printing, laser-based printing, droplet-based printing, magnetic field-based printing, and magnetic levitation-based printing. [3] [4] The optimal microgravity bioprinting technique is to utilize formative biofabrication, which is a combination of utilizing a magnetic and acoustic levitation field to fabricate tissues and organs. [5] The magnetic and acoustic levitation field creates a zone that acts like a scaffold to provide support for the bioprinting process. Bioinks used in microgravity bioprinting are specifically low viscosity compounds that can contain biomaterials and biological substances. [6] They function similarly to other 3D bioprinting processes but are optimized for zero gravity settings. Limitations of microgravity bioprinting are shared amongst other 3D bioprinting techniques. [7] An added challenge is sending biomaterials and bioinks to space when the supply on board the ISS has been extinguished.
An American-based company named Techshot printed the first cardiac and vascular tissue in a microgravity environment using a bioink consisting of adult human stem cells and a nScrypt bioprinter developed specifically for zero gravity use. [8] Techshot begins developing a specific microgravity use bioprinter to send to the International Space Station (ISS).
A Skolkovo-based company named 3D Bioprinting Solutions began manufacturing and developing a space specific bioprinter that utilized magnetic levitation technology. [9]
3D Bioprinting Solutions had successfully printed a mouse thyroid aboard the International Space Station (ISS) using their magnetic bioprinter. [10]
The bioprinted mouse thyroid was sent back to Earth in early 2019 for analysis. Biofabrication Facility, a microgravity bioprinter developed and produced by Techshot, was sent and installed onto the ISS. The Facility is designed to gradually print thicker tissues over time and conduct drug reformulation research. [11] 3D Bioprinting Solution's first human cell bioprinting was attempted in late 2019 aboard the ISS. [12] They successfully printed human bone tissue fragments using a magnetic nanoparticle mixture consisting of living human cells and calcium phosphate ceramics.
The microgravity environment enables the possibility of printing soft and delicate tissue structures such as the blood vessels. On Earth, the fragility of blood vessels result in the structure collapsing due to the cell weight combined with the force of gravity. Veins and arteries bioprinted in zero gravity do not require structural support and suspend in space during the print process. [13] This allows the delicate tissues to maintain their structure and shape throughout the entire printing process. Before sending the bioprints back to Earth, the tissues are conditioned using cell culturing systems to further strengthen the tissue for self-support. [14] Skipping the cell culturing will result in the soft tissue collapsing under gravitational force and cellular weight due to lack of cell stability. Once the cell culturing process is complete, the printed delicate tissue structures are expected to be functionally no different from their natural counterparts.
Complex organs can be fabricated solely out of cells and biological matter without the need of any support system. Zero gravity environment solves the mechanical load and structural requirement limitation that is common with 3D bioprinting on Earth. [15] The ISS currently runs multiple microgravity focused bioprinters to print cardiovascular tissues and structures . [16] The bioprinted tissues and structures are used as models for various research involving therapy development to treat heart diseases and repair damaged heart tissue. [17]
Biofabricated organs such as livers have been used as in vitro models to test and treat specific liver diseases due to their increased mimicry in physiological conditions. [18] Current liver models are limited to smaller tissue slices due to the increasing complexity of printing a larger liver construct. Microgravity bioprinting can potentially fabricate a larger and more complex liver construct that can function on par with natural livers.
A handheld device called the Bioprint FirstAid Handheld Bioprinter (Bioprint FirstAid) is being developed as a next generation handheld bioprinter that functions in both Earth and space. [19] The bioprinter aims to print a band-aid patch made out of bioinks containing cells of respective patients. The entire printing process takes about 10 minutes and relies purely on mechanical printing through a fed ink cartridge. This research is a start to developing portable and easy-to-use bioprinters that can function under any circumstance.
Chemical compounds can be fabricated with uniquely edited surface properties and characteristics in space that cannot be achieved on Earth. [20] Specially made compounds can be tested during research to note their effectiveness compared to compounds found on Earth. Zero gravity environment provides more efficient chemical compound manufacturing processes than regular manufacturing procedures. [21] This effects further optimizations and increased productions of drugs.
Microgravity Bioprinting utilizes the advantages of the zero gravity to print organ and tissue structures that are sensitive to gravitational and cellular weight. High viscosity bioinks are frequently used for bioprinting to allow cells to retain and form a 3D structure. [22] The high viscosity counteracts the force of the Earth's gravity but generates a high amount of shear stress. The increasing stress on these high viscosity bioinks during the printing process results in frequent cell death. The microgravity environment enables usage of low viscosity bioinks while still allowing the bioprint to form a fully cell based 3D structure. This removes the necessity of creating a scaffold for support since the cells are printed in a suspended state. As microgravity bioprinting improves and evolves, the possibility of printing artificial organs presents an opportunity to further space exploration and colonization. [23] Regenerative medicine is expected to improve drastically as Earth based biofabrication techniques become more refined based on the improvements and breakthrough from microgravity bioprinting. [24]
Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance, it can is considered as a field of its own.
Organ printing utilizes techniques similar to conventional 3D printing where a computer model is fed into a printer that lays down successive layers of plastics or wax until a 3D object is produced. In the case of organ printing, the material being used by the printer is a biocompatible plastic. The biocompatible plastic forms a scaffold that acts as the skeleton for the organ that is being printed. As the plastic is being laid down, it is also seeded with human cells from the patient's organ that is being printed for. After printing, the organ is transferred to an incubation chamber to give the cells time to grow. After a sufficient amount of time, the organ is implanted into the patient.
Anthony Atala is an American bioengineer, urologist, and pediatric surgeon. He is the W.H. Boyce professor of urology, the founding director of the Wake Forest Institute for Regenerative Medicine, and the chair of the Department of Urology at Wake Forest School of Medicine in North Carolina. His work focuses on the science of regenerative medicine: "a practice that aims to refurbish diseased or damaged tissue using the body's own healthy cells".
The Wake Forest Institute for Regenerative Medicine (WFIRM) is a research institute affiliated with Wake Forest School of Medicine and located in Winston-Salem, North Carolina, United States
Ali Khademhosseini is the CEO of the Terasaki Institute, non-profit research organization in Los Angeles, and Omeat Inc., a cultivated-meat startup. Before taking his current CEO roles, he spent one year at Amazon Inc. Prior to that he was the Levi Knight chair and professor at the University of California-Los Angeles where he held a multi-departmental professorship in Bioengineering, Radiology, Chemical, and Biomolecular Engineering as well as the Director of Center for Minimally Invasive Therapeutics (C-MIT). From 2005 to 2017, he was a professor at Harvard Medical School, and the Wyss Institute for Biologically Inspired Engineering.
The Methuselah Foundation is an American-based global non-profit organization based in Springfield, Virginia, with a declared mission to "make 90 the new 50 by 2030" by supporting tissue engineering and regenerative medicine therapies. The organization was originally incorporated by David Gobel in 2001 as the Performance Prize Society, a name inspired by the British governments Longitude Act, which offered monetary rewards for anyone who could devise a portable, practical solution for determining a ship's longitude.
Weightlessness is the complete or near-complete absence of the sensation of weight, i.e., zero apparent weight. It is also termed zero g-force, or zero-g or, incorrectly, zero gravity.
David Gobel is an American philanthropist, entrepreneur, inventor, and futurist. He is co-founder and CEO of the Methuselah Foundation, CEO of the Methuselah Fund, and one of the first to publicly advance the idea of longevity escape velocity, even before this term was formulated.
In tissue engineering, neo-organ is the final structure of a procedure based on transplantation consisting of endogenous stem/progenitor cells grown ex vivo within predesigned matrix scaffolds. Current organ donation faces the problems of patients waiting to match for an organ and the possible risk of the patient's body rejecting the organ. Neo-organs are being researched as a solution to those problems with organ donation. Suitable methods for creating neo-organs are still under development. One experimental method is using adult stem cells, which use the patients own stem cells for organ donation. Currently this method can be combined with decellularization, which uses a donor organ for structural support but removes the donors cells from the organ. Similarly, the concept of 3-D bioprinting organs has shown experimental success in printing bioink layers that mimic the layer of organ tissues. However, these bioinks do not provide structural support like a donor organ. Current methods of clinically successful neo-organs use a combination of decellularized donor organs, along with adult stem cells of the organ recipient to account for both the structural support of a donor organ and the personalization of the organ for each individual patient to reduce the chance of rejection.
Three dimensional (3D) bioprinting is the utilization of 3D printing–like techniques to combine cells, growth factors, bio-inks, and biomaterials to fabricate functional structures that were traditionally used for tissue engineering applications but in recent times have seen increased interest in other applications such as biosensing, and environmental remediation. Generally, 3D bioprinting utilizes a layer-by-layer method to deposit materials known as bio-inks to create tissue-like structures that are later used in various medical and tissue engineering fields. 3D bioprinting covers a broad range of bioprinting techniques and biomaterials. Currently, bioprinting can be used to print tissue and organ models to help research drugs and potential treatments. Nonetheless, translation of bioprinted living cellular constructs into clinical application is met with several issues due to the complexity and cell number necessary to create functional organs. However, innovations span from bioprinting of extracellular matrix to mixing cells with hydrogels deposited layer by layer to produce the desired tissue. In addition, 3D bioprinting has begun to incorporate the printing of scaffolds which can be used to regenerate joints and ligaments. Apart from these, 3D bioprinting has recently been used in environmental remediation applications, including the fabrication of functional biofilms that host functional microorganisms that can facilitate pollutant removal.
SpaceX CRS-4, also known as SpX-4, was a Commercial Resupply Service mission to the International Space Station (ISS), contracted to NASA, which was launched on 21 September 2014 and arrived at the space station on 23 September 2014. It was the sixth flight for SpaceX's uncrewed Dragon cargo spacecraft, and the fourth SpaceX operational mission contracted to NASA under a Commercial Resupply Services contract. The mission brought equipment and supplies to the space station, including the first 3D printer to be tested in space, a device to measure wind speed on Earth, and small satellites to be launched from the station. It also brought 20 mice for long-term research aboard the ISS.
Magnetic 3D bioprinting is a methodology that employs biocompatible magnetic nanoparticles to print cells into 3D structures or 3D cell cultures. In this process, cells are tagged with magnetic nanoparticles that are used to render them magnetic. Once magnetic, these cells can be rapidly printed into specific 3D patterns using external magnetic forces that mimic tissue structure and function.
Organovo Holdings, Inc. is an early-stage medical laboratory and research company which designs and develops functional, three dimensional human tissue for medical research and therapeutic applications. Organovo was established in 2007 and is headquartered in San Diego, California. The company uses its internally developed NovoGen MMX Bioprinter for 3D bioprinting.
Ethics of bioprinting is a sub-field of ethics concerning bioprinting. Some of the ethical issues surrounding bioprinting include equal access to treatment, clinical safety complications, and the enhancement of human body.
4-dimensional printing uses the same techniques of 3D printing through computer-programmed deposition of material in successive layers to create a three-dimensional object. However, in 4D printing, the resulting 3D shape is able to morph into different forms in response to environmental stimulus, with the 4th dimension being the time-dependent shape change after the printing. It is therefore a type of programmable matter, wherein after the fabrication process, the printed product reacts with parameters within the environment and changes its form accordingly.
Bio-inks are materials used to produce engineered/artificial live tissue using 3D printing. These inks are mostly composed of the cells that are being used, but are often used in tandem with additional materials that envelope the cells. The combination of cells and usually biopolymer gels are defined as a bio-ink. They must meet certain characteristics, including such as rheological, mechanical, biofunctional and biocompatibility properties, among others. Using bio-inks provides a high reproducibility and precise control over the fabricated constructs in an automated manner. These inks are considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM).
The ISS U.S. National Lab, commonly known as the ISS National Lab, is a U.S. government-funded national laboratory established on 30 December 2005 by the 2005 NASA Authorization Act. With principal research facilities located in the United States Orbital Segment (USOS) of the International Space Station (ISS), the Laboratory conducts research in life sciences, physical sciences, technology development and remote sensing for a broad range of academic, government and commercial users. Of the 270 payloads that the Center for the Advancement of Science in Space (CASIS) has sent to the ISS, 176 have been for commercial companies including Merck & Co., Novartis, Eli Lilly and Company, Hewlett Packard Enterprise, Honeywell, and Procter & Gamble.
Bico Group is a bioconvergence startup that designs and supplies technologies and services to enhance biology research. It focuses on commercializing technologies for life science research as well as bioprinting, and its products often combine capabilities in artificial intelligence, robotics, multiomics, and diagnostics.
Bioprinting drug delivery is a method based on the use of three-dimensional printing of biomaterials through an additive manufacturing technique to develop drug delivery vehicles that are biocompatible tissue-specific hydrogels or implantable devices. 3D bioprinting uses printed cells and biological molecules to manufacture tissues, organs, or biological materials in a scaffold-free manner that mimics living human tissue to provide localized and tissue-specific drug delivery, allowing for targeted disease treatments with scalable and complex geometry.
Space pharmacology is the application of biomedical engineering that studies the use and dynamics of drugs or pharmaceuticals in space environments. Falling in the realm of space medicine, outer space drug delivery is the practical application of using drugs to treat disorders that may arise due to space’s extreme conditions, such as microgravity, radiation, and other physiological and psychological risks. The physical conditions and hazards posed by outer space conditions can result in space-related disorders to the human body, posing a necessity to manufacture, modify, and test drugs to work in outer space.