“3D Bioprinting” or “bioprinting” promise Human organs and tissues, for medical use in harsh military environments

Rajesh Uppal June 21, 2023 BioScience, Manufacturing, Military Comments Off on “3D Bioprinting” or “bioprinting” promise Human organs and tissues, for medical use in harsh military environments 535 Views

In the UK, there are some 7,000 people on the list who are in dire need of organ transplants and In the US, the number awaiting transplant is around 120,000, with 20 dying each day for want of an organ. There is a large and growing need for an alternative to the organ transplant waiting list.

To alleviate this problem, Scientists have turn to lab grown organs. Further growing artificial organs is further enabled through 3D printing or bioprinting which promises to bring the speed, flexibility, and customization.

“3D Bioprinting” or “bioprinting” is a form of additive manufacturing that uses cells and biomaterials instead of traditional metals and plastics to create 3D constructs that are functional 3D tissues. These biomaterials are called bioinks, and they mimic the composition of our tissues. Bioprinting can be applied to a variety of areas including but not limited to regenerative medicine, drug discovery and development, and 3D cell culture.

Current organ transplant patients have to take immunosuppressant drugs all their life to prevent the body rejecting the new addition whereas using human cells, specifically those from the same patient, would reduce any possibility of rejection.

For pharmaceutical development, 3D bioprinting offers a means of testing drugs faster, at a lower cost, and with better biological relevance to humans than animal testing. In the biomedical devices field, 3D bioprinting has enabled new developments such as sugar stents to help surgeons join veins with fewer complications, and systems for improved drug delivery, among others.

3D printing in future could let physicians print structures made of human cells — from tiny structures like ‘organs on a chip’, to huge ones like whole replacement organs. Bioprinted organs made from an individuals’ own tissue won’t be rejected by their body, will last far longer, won’t need anti-rejection meds, and can be custom made to the individual’s exact measurements — whether they’re a four year old or a NFL linebacker.

The first human corneas to come out of a low-cost 3D printer were created by a team of researchers at Newcastle University in the UK. However, not all human organs are created equally — or can be created by bioprinting, for that matter. Flat tissues, like skin, and hollow ones, like the stomach or bladder, are relatively easy to print, whereas complex solid organs — the heart, liver, or pancreas — would be far harder to recreate with printing due to the rich blood supply they need.

The common challenge shared by all tissue engineers is what is known as vascularization. Scientists have struggled to create the intricate networks of tiny blood vessels that carry nutrients and oxygen deep into organs and carry waste products out. The bigger an organ is, the more blood supply it needs to bring organs and nutrients to the tissue. Large organs need a complex web of interconnected, different-sized arteries, capillaries, and veins. The walls of the vessels need to be strong enough to withstand the normal flow of blood through them without causing clots, and need to be made of specific layers. For now, it’s too much complexity for 3D bioprinters to manage.

That’s why most demonstrations thus far have been of organelles just an inch or two across or hollow structures like throats or bladders. But latest research has even surmounted this last difficulty paving the way of commercializing 3d printing of human organs.

Recently, a team of American researchers led by scientists at Rice University in Texas have created a 3D bioprinter that can print vessels less than a third of a millimeter wide in biocompatible hydrogels. In a paper in Science they describe how they used the bioprinter to create a model of the human lung that can effectively oxygenate human blood. “I think within ten years we won’t see any more heart transplants, except for people with congenital heart damage, where only a new heart will do,” Stephen Westaby, from the John Radcliffe Hospital in Oxford, told The Telegraph.

Now, Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online in Tissue Engineering Part A May 2019 , is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

While researchers are working on how to print full-size organs, the tiniest bioprinted structures are already helping researchers. Bioprinting can also be used to make ‘organs on a chip’ — tiny samples of tissue that mimic the functions and structures of their full-grown counterparts. These mini organs allow pharmaceutical companies to test drugs on versions of human tissues, and assess their effectiveness or toxicity instead of using unreliable and ethically difficult animal models.

One day, organs on a chip could be made using individuals’ own cells to test potential therapies. Rather than using the same standard treatments for every patient, by taking some cells, culturing them and printing them onto the chip, physicians can have a unique view into how their patient will react to a particular drug without having to start them on a whole course of it.

“These miniature human organs we can use for drug discovery, direct toxicity testing, and personalised medicine, BCS modelling and personalised medicine. We’ve taken the same strategy, and by using the same printers, we can print miniature structures that replicate the normal human response,” Dr Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine says.

While HP’s printers are more associated with offices rather than labs, HP also sells printers to the life sciences industry with its D300 BioPrinter line which prints drugs instead of documents. The machines are typically used in small to medium pharmaceutical companies in secondary drug discovery, where compounds thought to be effective against a particular disease are tested to see if they have any affect against the condition, and if so, at what dose.

The bioprinters are also being used elsewhere in the fight against coronavirus. HP has donated four of the D300e BioPrinters to four research facilities working on COVID-19: the Spanish National Research Council, the Monoclonal Antibody Discovery Laboratory at Fondazione Toscana Life Sciences in Italy, the US Center for Nuclear Receptors and Cell Signaling (CNRCS) at University of Houston, and France’s Grenoble Alpes University Hospital. Between them, the facilities are using the machines for research into the fundamental biology of COVID-19, monoclonal antibodies and other potential therapeutic candidates, and work on immunisation.

The success of bioprinting could become the key enabler that personalized medicine, tissue engineering, and regenerative medicine need to become a part of medical arsenals. Breakthroughs in bioprinting will enable faster and more efficient patient care and recovery. Biofabrication could be used to reshape the foundations of drug development, medicine, cosmetics, organ transplantation, and many other fields. It will transform the way doctors repair damaged ligaments, recreate tissues, and even reproduce the layers of the skin. The future of healthcare is likely to be 3D printed.

3D Bioprinting technology

The technology behind the bioprinters vary. Nonetheless, to date, the three main and most popular bioprinting technologies are extrusion, inkjet, and laser-based bioprinting. Some mainstream examples are: Some manufacturers, like Cellink or Allevi, use pneumatic-driven extrusion systems that pump high-pressure air in a cartridge to force bioinks to flow through a nozzle. Other fabrication systems, such as the one designed by Poietis has laser-assisted bioprinting that allows cells to be positioned in three dimensions with micrometric resolution and precision to design living tissue. Another type of bioprinting technology uses a stereolithography-based bioprinting platform. Vendors using this process include Volumetric and Cellink’s jointly produced Lumen X projection stereolithography based bioprinter.

3D bioprinting starts with a model of a structure, which is recreated layer-by-layer out of a bioink either mixed with living cells, or seeded with cells after the print is complete. These starting models can come from anywhere – a CT or MRI scan, a computer generated design (CAD) program, or a file downloaded from the internet.

That 3D model file is then fed into a slicer – a specialized kind of computer program which analyzes the geometry of the model and generates a series of thin layers, or slices, which form the shape of the original model when stacked vertically. Cura and slic3r are examples of slicers commonly used in 3D printing

Once a model is sliced, the slices are transformed into path data, stored as a G-code file, which can be sent to a 3D bioprinter for printing. In most cases, a three-axis mechanical platform controls the movements of extruders printing the bioink in the required algorithm and shape. This platform’s movement is governed by coordinates created by the designer and saved in a file format such as g-code that could be easily followed by the printer.

The bioprinter follows instructions in the G-code file in order, including instructions to control for temperature of the extruders, extrusion pressure, bed plate temperature, crosslinking intensity and frequency, and, of course, the 3D movement path generated by the slicer. Once all of the G-code commands are completed, the print is done and can be cultured or seeded with cells as part of a biostudy.

The process of bioprinting human tissue is a bit more involved. First, you have to get some stem cells from the person who needs the new organ, culture them in the right biochemical soup until you’ve got enough, then turn them into a bioink that can be extruded through a nozzle that’s two microns thick (or one 80th the size of a human hair). The bioink will be pushed through the printer, usually onto a scaffold made of hydrogel. A bit more culturing, and you could have a useable tissue that can either be printed directly onto the patient in an operating theatre, or built in a lab and then implanted.

Due to vantages such as precise deposition, cost-effectiveness, simplicity, and cell distribution controllability, 3D bioprinting development and application has been increasing constantly over the past few years.

As an additive manufacturing technique, 3D bioprinting is based on deposition of biomaterials, either encapsulating cells or loaded with cells later on, in micrometer scale to form subtle structures comparable to tissue. The materials range from basic biopolymers to extracellular matrices (think collagen) to living cells. There are not an infinite number of biomaterials, but there are a lot and each has its own conditions that need to be controlled for printing.”

As a result, need for new bioinks providing required properties for successful printing, such as printability, printing fidelity, and mechanical properties has been rising leading to extensive work to develop new materials. Choosing which bioink to use can be challenging. To date, we have witnessed researchers using bioinks based on several biomaterials, such as alginate, gelatin, collagen, silk, hyaluronic acid, even some synthetic-biomaterials-based-bioinks. The biomaterials can also use a patient’s own cells, adult stem cells, manipulating them to recreate the required tissue. The ability to program patient-specific cells is the beginning of customized bioprinting since the unlimited potential of these cells can be used to regenerate or repair damaged tissue.

Another project that could revolutionize the way surgical procedures are performed is handheld bioprinters; these systems enable surgeons to deploy cells — or material to aid in cellular growth — directly into a defect site in the body, such as severely burnt skin, corneal ulcerations or bone. One of the most talked-about handheld bioprinters has been Australia’s University of Wollongong BioPen, allow surgeons to repair damaged bone and cartilage by “drawing” new cells directly onto bone in the middle of a surgical procedure. Although still in pre-clinical trials, these devices have attracted the attention of healthcare practitioners due to its versatility.

Our artificial cornea breakthrough could lead to self-assembling organs

Over the last decade, scientists have been testing artificial corneas made from synthetic collagen gel. One of the difficulties is in getting the gel to take the right curved shape to fit the eye and focus light so the patient can see again. Martina Miotto, Post-Doctoral Researcher in Tissue Engineering, Newcastle University and her colleagues have developed a technology can gradually expand what we can achieve with bio-synthetic organs and tissues, bringing hope to the millions of people waiting for transplants.

Their group previously showed that collagen gels containing corneal cells contracted less when certain molecules (called peptide amphiphiles) were added. From this observation, they were able to design the gel mixture to contract by different amounts in different places to adopt a specific shape. Recently they found a way to make gel containing live corneal cells self-assemble into the correct pattern, like a piece of paper that folds itself into an origami design.

“In this particular case, we created a circular shape divided into two rings, with peptide amphiphiles located either in the outer ring or in the centre. In both cases, one part contracted more than the other and this difference caused the gel to progressively curve over five days until it reached a cornea-like shape.” The live cells that we added to the collagen acted like micro-actuators, microscopic engines exerting a contracting pull force. Each cell’s force is tiny but together they can shape a one inch-wide block of tissue into a cornea-like structure.

It might be possible to use this technique to create other artficial tissues from organs that normally contain cells that are able to contract. Heart, skin, muscle and blood vessel tissues could be theoretically reproduced using this technology.

“My colleagues, led by Professor Che Connon, have already managed to 3D print a full artificial cornea. Eventually, 3D printers may be able to reproduce far more complex biological structures by building them up layer by layer. For instance, to create the multiple chambers of a heart, bio-ink containing heart cells from a patient would by printed onto a biodegradable scaffold that can later be removed by heat to leave a fully biological heart ready for transplantation. ”

“But it’s also possible to take this technology one step further with the invention of 4D printing, the printing of structures that can self-assemble by folding after the manufacturing process is done, just like our corneas. Printing biological structures that can arrange themselves into an even more complex shape would mean you wouldn’t need to produce scaffolds to print the cells on, or remove them afterwards. The accuracy of the printing process would be extremely useful in precisely positioning the peptide-based molecules that make the cells contract within the bio-material.”

Full 4D printing of complete organs might still be relatively far into the future. But in the meantime, we can also look at how the technology could help develop new, more efficient smart materials. The process could be used to create shape-changing stents to keep clogged blood vessels open. A closed stent could easily be injected into the bloodstream and then made to open up by the contracting force of cells at a site of injury, avoiding the need for surgery. In general, the range of possible applications of bio-responsive, self-folding materials is vast.

3D printed EYES

The first human corneas to come out of a low-cost 3D printer were created by a team of researchers at Newcastle University in the UK. Che Connon, professor of tissue engineering at Newcastle University, praised the medical breakthrough for utilising cheap materials in the process. Professor Connon said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3-D printer. “This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. “Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.” The corneas is a crucial element in the outer layers of the eye used to focus vision and it is estimated some five million people suffer blindness due to cornea related wounds and diseases.

Scientists have now developed a solution in the form of so-called bio-ink – a liquid mix of stem cells, collagen and alginate acid. With a simple 3D printer the Newcastle scientists were able to print an artificial human cornea in less than 10 minutes. The cornea printing method could in turn create an unlimited supply of corneas ready for transplanting.

3D printing EAR

Cornell bioengineers and physicians have created an artificial ear that looks and acts like a natural ear, giving new hope to thousands of children born with a congenital deformity called microtia. Physicians managed to 3D print a realistic ear using living cells from cows and collagen from rat tails. The process is also fast, “It takes half a day to design the mold, a day or so to print it, 30 minutes to inject the gel, and we can remove the ear 15 minutes later, “ said co-lead author Lawrence Bonassar, associate professor of biomedical engineering.

The novel ear may be the solution reconstructive surgeons have long wished for to help children born with ear deformity, said co-lead author Dr. Jason Spector, director of the Laboratory for Bioregenerative Medicine and Surgery and associate professor of plastic surgery at Weill Cornell. “A bioengineered ear replacement like this would also help individuals who have lost part or all of their external ear in an accident or from cancer,” Spector said. For people missing an ear, the reconstruction process is slow and painful, involving harvesting cartilage from the patient’s ribs. However, new techniques might make it easier.

Working livers

A research team from Utrecht University has successfully fabricated working livers using a newly developed ultrafast volumetric 3D bioprinting method.

By means of visible light tomography, the volumetric bioprinting method enabled the successful printing of miniature stem cell units by making the cells “transparent”, which meant they retained their resolution and ability to perform biological processes.

Printed in less than 20 seconds, the liver units were able to perform key toxin elimination processes mimicking those that natural livers perform in our bodies, and could open new opportunities for regenerative medicine and personalized drug testing.

Ultrafast volumetric 3D bioprinting

The Utrecht team first demonstrated their volumetric bioprinting technique in 2019 with the creation of free-form tissue structures. The method differs from current bioprinting processes which are based on layer-by-layer deposition and assembly of repetitive building blocks, such as cell-laden hydrogels and scaffolds.

Instead, the volumetric bioprinting method involves projecting a series of 2D light patterns into a cylindrical container filled with cell-laden photoresponsive hydrogel, which triggers polymerization. One of the key benefits of the layerless, nozzle-free technique is that it poses no harmful mechanical stress on the cells, and is also capable of fabricating tissues at rapid speeds.

The work in 2019 prompted the spin-off of Readily3D, a manufacturer of volumetric 3D bioprinters, which announced its participation in the European ENLIGHT project last year. Readily3D is playing its part in the €3.6M project to 3D print a living model of the human pancreas in order to improve the testing of diabetes medication.

Bio-printed artificial vascular networks

Now, though, a team of American researchers led by scientists at Rice University in Texas have created a 3D bioprinter that can print vessels less than a third of a millimeter wide in biocompatible hydrogels. In a paper in Science they describe how they used the bioprinter to create a model of the human lung that can effectively oxygenate human blood.

The group used a common 3D printing technique called projection stereolithography, which uses light to solidify light-sensitive resins layer by layer. In this case, they used a solution that converts into a soft hydrogel when exposed to blue light. A special projector shines high-resolution patterns of light from below that determine the structure of each 2D slice. An overhead arm then lifts the growing model so the next layer can be generated.

Generating high-resolution light patterns is fairly simple, but the challenge is to make the resin sensitive enough to replicate those minute details. The key discovery was that a common food dye called yellow No. 5 could effectively absorb blue light while confining the solidification to a very fine layer. Coming from the food and beverage industry, the chemical is also completely non-toxic.

They used the approach to create an intricate model of the lung with tiny air-sacs surrounded by fine blood vessels. In experiments they showed the artificial organ could oxygenate human blood. And to demonstrate that the technology could one day be used in humans, they also used print tissue carriers and loaded them with liver cells before implanting them into mice.

The Rice University-led team are not the only ones working on this problem. Startup Prellis Biologics is also working on bioprinting minute capillary blood vessels, and last December they launched a line of tissue scaffolds with built-in capillaries.

“These interpenetrating networks are physically and biochemically entangled, and the architecture itself is intimately related to tissue function. Ours is the first bioprinting technology that addresses the challenge of multivascularization in a direct and comprehensive way,” he said.

High-tech ‘bio-printer’ bio-prints artificial vascular networks

Scientists from the Universities of Sydney, Harvard, Stanford and MIT have bio-printed artificial vascular networks mimicking the body’s circulatory system that are necessary for growing large complex tissues. Using a high-tech ‘bio-printer’, the researchers fabricated a multitude of interconnected tiny fibres to serve as the mold for the artificial blood vessels.

They then covered the 3D printed structure with a cell-rich protein-based material, which was solidified by applying light to it. Lastly they removed the bio-printed fibres to leave behind a network of tiny channels coated with human endothelial cells, which self-organized to form stable blood capillaries in less than a week. The study reveals that the bio printed vascular networks promoted significantly better cell survival, differentiation and proliferation compared to cells that received no nutrient supply.

But while solving the blood supply problem has been top of wish list for tissue engineers, the authors of the latest study point out that the circulatory system isn’t the only place where these fine structures exist. “Our organs actually contain independent vascular networks—like the airways and blood vessels of the lung or the bile ducts and blood vessels in the liver,” says Jordan Miller, assistant professor of bioengineering at Rice University and senior author of the Science paper.

Living Skin Can Now Be 3D-Printed With Blood Vessels Included

Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published in Tissue Engineering Part A, in Nov 2019 is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

“Right now, whatever is available as a clinical product is more like a fancy Band-Aid,” said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), who led this research at Rensselaer. “It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells.” A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.

In this paper, the researchers show that if they add key elements — including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells — with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks.

Easy to use 3D bioprinting technique creates lifelike tissues from natural materials

Bioengineers at the University of California San Diego have developed a 3D bioprinting technique that works with natural materials and is easy to use, allowing researchers of varying levels of technical expertise to produce lifelike organ tissue models. As a proof of concept, the UC San Diego team used their method to create blood vessel networks capable of keeping a breast cancer tumor alive outside the body. They also created a model of a vascularized human gut. The work was published recently in Advanced Healthcare Materials.

The goal isn’t to make artificial organs that can be implanted in the body, researchers said, but to make easy-to-grow human organ models that can be studied outside the body or used for pharmaceutical drug screening. “We want to make it easier for everyday scientists — who may not have the specialization required for other 3D printing techniques — to make 3D models of whatever human tissues they’re studying,” said first author Michael Hu, a bioengineering Ph.D. student at the UC San Diego Jacobs School of Engineering. “The models would be more advanced than standard 2D or 3D cell cultures, and more relevant to humans when it comes to testing new drugs, which is currently done on animal models.”

Russian Scientists Create 3D Printer So Precise It’s Able to Print Human Organs

Physicists from the Russian Academy of Sciences’ Crystallography & Phonetics Scientific Research Center have found a solution to the long-standing problem of 3D printers’ low resolution and slow operation, creating special nanoparticles which form complex bonds with the help of ultraviolet beams driven by conventional infrared lasers. According to the scientists, whose findings were published in the Scientific Reports academic journal, the nanoparticles allow for the speedy printing of three dimensional structures of any shape and size.

“This idea can be used for biomedical purposes, including tissue engineering, and replacing damaged parts of organs and tissue with the help of various polymer materials,” study coauthor Kirill Khaydukov explained. “We expect that our technology will allow us to create designs with the right sizes and properties inside living tissue to repair damage,” he added.

Over the past decade, scientists and engineers around the world have created 3D printers capable of printing everything from traditional plastics to metals to living cells. But the traditional setback of the technology has been its low resolution and slow operation, which results from the printers’ layer-by-layer method of operation. Khaydukov and his colleagues’ special nanomaterials solve both these problems, creating an extremely high-grade 3D printer. UV rays act on the 3D printers’ tiny building blocks, forcing them to link up in chains.

The scientists also solved the problem of the shallow penetration of UV light into the building material with the help of nanoparticles consisting of sodium, thulium ytterbium and fluorine, which allows for the UV light to be distributed evenly throughout the 3D structure and hence ensuring strong bonds.

The scientists say their invention is fully compatible with existing polymer materials used by today’s 3D printers. They believe their idea will find uses in 3D laser drawing, materials processing at a micro level, and holography, as well as electronics and data processing systems.

Ruggedized 3D printers for medical use in harsh military environments

A recent pilot program conducted by the Uniformed Services University (USU) of the Health Sciences shows that 3D printers can be deployed in desert and remote environments to fabricate medical tools and biomaterials, where it’s not practical to have soldiers carry hundreds of medical supplies in their packs.

The pilot program, called Fabrication in Austere Environments, was developed under USU’s federally-funded 4-Dimensional Bioprinting, Biofabrication, and Biomanufactuing (4D Bio3) Program, along with the U.S. Military Academy at West Point, the Geneva Foundation as well as two manufacturers — 3D printer maker NScrypt, Inc. and commercial space company Techshot, Inc. The goal is to fabricate medical products and tissues in harsh environments with a ruggedized 3D printer. Announced in 2018, the five-year program is tasked with researching, developing, and applying new bioprinting, biofabrication, and biomanufacturing technologies.

The first 3D printer deployed and tested in harsh environments was nScrypt’s heavier and larger ruggedized 3D bioprinter, called nRugged, which was developed for the U.S. Army. “ABAT [Austere BioAssembly Tool] or nRugged is a lightweight and ruggedized bioprinter that was custom built by nScrypt that was based off of the [Techshot’s] BioFabrication Facility (BFF) [3D bioprinter] that is on the International Space Station (ISS),” said Church. “It is made out of a carbon fiber material and is mostly used for DoD [Department of Defense] applications. This printer is configurable for printing biologics and non-biologics. It has the capability to print with any of our gizmos (Smartpump, nFD, nMill, and nPnP360). We can print over 10,000 commercial materials with this tool and it can be used for a plethora of different applications.”

nScrypt has worked with the U.S. Army on 3D printers for austere environments for several years, explained Church. “nRugged was specifically developed in partnership with West Point (Lt. Col. Jason Barnhill) and USU/4D Bio3 and the Geneva Foundation.” The nScrypt 3D bioprinter, as part of the company’s Factory in a Tool (FIT), can be configured to do both 3D printing and bioprinting. nRugged has “four tools that can change automatically,” said Dr. Kenneth Church, nScrypt’s CEO. Swapping out with other tools can be done if needed, “but these four tools provide mechanical, electrical, and biological properties,” he added. Field tests have included 3D printing a scalpel handle and a surgical model of a T9 vertebrae as well as bioprinted bioactive bandages and meniscus.

The nRugged printer has demonstrated a variety of electronic sensor structures and structural bandages with antibiotic layers, said Church. “We have also printed diverse 3D structures that look and feel like bone. These are biocompatible materials that are implantable.” The next step is to develop a smaller and lighter version that can fit in a soldier’s pack. Church said the plan is to make something “light and one-man portable” as well as to make a larger 3D printer “but hopefully still light.” Some of the work ahead includes continuing to develop sensors and sensor systems using the nScrypt machines as well as implementing sensor systems in the 3D printers.

“If you precisely place diverse materials down to micron precision, you can make truly functional electronic structures. These electronic structures could be sensors with a Bluetooth comms in any shape or you could make a bandage with biological and cellular materials for wound healing. But to do this, precision matters and we handle that now with structure, mass, mechanics, and electronics,” said Church. “As we progress we will offset the structure and mass with microelectronics and sensors in a closed loop system to obtain that much needed precision,” he added.

Church said it is easy to print forceps, handles for scalpels, clamps, and other surgical instruments as well as rigid braces or flexible wraps, and to add biological or antibacterial materials embedded in them. “The holy grail is to print the necessary cells, extracellular matrices, and biopolymers that will lead to tissue growth and with the right complexity lead to full organ growth,” he said. Many, including the nScrypt team “are blazing a tissue engineering trail and taking on the challenge for a portable printer to print bio bandages, wraps, and composite braces,” said Church.

These will be sensorized devices, incorporating electronics and sensors, for example, in an injured soldier’s cast or brace to monitor the wound. A smartphone will be used to communicate with these devices to retrieve the data. “As we get more sophisticated, think electronics and sensors in the casts and braces to monitor the wound. To stop bleeding, something personalized will function more effectively than just pressure or tying it off,” said Church. “We, together with research, medical doctors, and research 3D tool developers, will advance tools and medicine in the field; it will become fast, much more effective, and strike within the golden hour. Today, we can still show improvement by printing simple devices that make the small difference.”

3D printing in space

Now researchers are looking to print organ-like tissues in space that could lead to 3D printing human organs for transplants. In partnership with nScrypt, Techshot developed its spaceflight-qualified BFF 3D bioprinter, which was later used to help develop the nRugged printer for soldiers in the battlefield. The BFF bioprinter was first launched in 2019 to the International Space Station (ISS) and is the first American bioprinter in space. Techshot’s first of two planned menisci (knee cartilage) prints in space for USU’s 4D Bio3 Program was successfully tested in April 2020. The first experiment aboard the ISS U.S. National Laboratory tested the materials and processes required to print a meniscus in space.

Rich Boling, vice president, corporate advancement, at Techshot, believes the BFF also could be used to print medical supplies to aid injured astronauts on long-duration deep space missions as well as feed them by printing meat with animal cells cloned in space with a new payload. Currently under development is the Techshot Cell Factory that will enable continuous generation of multiple cell types in space that can be used for 3D printing and other uses, and the Techshot FabLab that will be used as a multi-material fabrication lab to make 3D-printed objects in space from plastics, metal, ceramics, and electronics. “The BFF can print with the cells that the Cell Factory will make in space,” said Boling. “We’re also building a large 3D printer for use in deep space that can manufacture high-strength aerospace-grade metals, plus electronics [via the Techshot FabLab].”

Any entity – private, public, or academic – can join as collaborators of the USU 4D Bio3 program to help achieve the program goals of researching and applying new fabrication technologies on Earth or in space. This includes making the portable and lightweight 3D printer with smartphones and/or Bluetooth communications that the soldiers can put in their packs. It is hoped the 4D Bio3 program will be extended beyond the end date of 2023.

Manufacturers

A few of the main manufacturers supplying the market include 3D Bioprinting Solutions, Allevi, Aspect Biosystems, Cellink, nScrypt, regenHu, Inventia, Regemat3D, Poietis, and more. Last year, 3DPrint.com counted 111 established bioprinting firms around the world. Mapping the companies that make up this industry is a good starting point to understand the bioprinting ecosystem, determine where most companies have established their headquarters and learn more about potential hubs, like the one in San Francisco.