3D biofabrication of meat: myth or reality?
The risk has never been higher than in recent times as brave and passionate entrepreneurs attempt to pave the way for this new world of three-dimensional (3D) lab-grown cell cultivated, plant-based & hybrid meat, fish, and other food alternatives. The demand for alternative meat and the removal of animals from the supply chain is at an all-time high. In terms of the market potential, it is enormous. One report from Edison suggested that the demand for cultivated meat, a section of the more prominent alternative meat market, is expected to reach $600 billion by 2040, with a compound annual growth rate of 41%. The market has some highly innovative and successful companies innovating in food (Upside Foods, Shiok Meats, Meatable, MosaMeats, Higher Steaks, Fisheroo, Umami, BlauNanu, Aleph Farms, Just, Mission Barns, to name a few). The Netherlands is taking the lead from a country perspective with a national growth fund of 60 million EUR for meat alternatives granted this year. Similarly, the same smaller funds appear in California. Plant-based meat alternatives are officially cheaper in the Netherlands than existing meat, creating a significant change in the industry.
In the 1950s, Dutch researcher Willem van Eelen independently came up with the idea for cultured meat, and the first 3D hamburger was made in a lab by Dutch company Mosa Meat founders in 2013. In terms of origin stories, the present world of cultivated meat is a direct result of decades of 3D tissue engineering research & technologies (cell culture, stem cells, bioreactors, hardware, advanced technologies) under the scope of regenerative medicine. I have followed the founders and pioneers of this cell-cultivated meat industry for years; what they have achieved is phenomenal. I fondly remember meeting the CTO of Meatable twice around 2017/2018 and listening to his passionate story, showcasing the visuals of faster cell growth, and pointing to gin bioreactors explaining the future lies similarly with cell-cultivated meat. The founders embodied the same spirit as other young passionate entrepreneurs with nothing more than access to some IP, a solid business plan, and a vision. Since then have achieved enormous success raising over 60 million EUR of funding and aiming to release products by 2025.
This development shows how long the path can be from science to actual viable commercialization of a product. We often underestimate the complexity of tech transfer and all the factors that need to come together to make it a successPrince Constantijn Van Orange-Nassau of the Netherlands, Envoy for Tech Leap & Co-Founder of StartupFest Europe.
There could even be a second wave of start-ups on the horizon with Roslin Technologies releasing iPSC stem cell products to make meat and companies like NouBio with commercially available serum-free media that is 95% more cost-efficient than Fetal Bovine Serum [FBS], with no animals harmed, & no need for FDA or USDA approval for cell-cultivated meat production. This approach opens up the industry to even more cultivated meat players. So the focus of existing companies is that they should start to collaborate or co-develop with advanced 3D & 4D tissue engineering technologies and shift towards what can make truly complex and scalable meat a reality.
OuroFoods have entered the market led by Dr. Elizabeth Bennett with access to disruptive bio-electric field 3D tissue engineering & 4D biofabrication technologies [Exclusive license with Ourobionics BV] that are individually proven & published to be 30X faster than extrusion (one module), no cell damage like extrusion, and cells maintain all cellular properties to make 3D tissue. The technologies allow for animal cell, protein, and flavor molecule level components to be bio-encapsulated during the biofabrication process, & have a nanoscale resolution for enhanced complex meat scaffolding to scale cell growth. They are fully scalable (1000X) for industry-level production while remaining cost-efficient. The Founder/CEO of OuroFoods, Dr. Bennett, and the Founder/CEO of NouBio, Dr. Samad Ahadian, are open to co-develop with many other players in the industry with joint goals of building their companies between California and the Netherlands. OuroFoods and NouBio are closing their seed rounds by the end of 2023.
“The only way that we’ll remove animals from the supply chain, improve human health, and walk our planet back from the edge of oblivion is to make a protein with a higher value proposition to mainstream consumers than slaughtered meat. We’re hoping people will sacrifice authentic meatiness, a short ingredient list, and a fair price for ethical reasons. Ouro Foods is making a protein that tastes meatier, feels meatier, and can be optimized for without filler ingredients,” said Dr. Elizabeth Bennett; Founder and CEO of OuroFoods.
We have previously seen the next generation of researchers and start-ups utilizing standard extrusion-based 3D bioprinting to create plant and cell-based meat. Now there is a breath of fresh air in the industry with more advanced, faster, nanoscale and proven 3D/4D tissue engineering technologies. It is a pivotal moment when those with decades of experience in tissue engineering and regenerative medicine enter the industry. Redefine Meat and Meatech3D are two clear trailblazers in this 3D food printing industry using basic extrusion technologies, alongside others such as Novameat, RevoFoods, Coccuus, and SavourEat. Meatech3D has recently partnered with Umami meats.
3D biofabrication of meat by extrusion bioprinting has achieved something new and inspiring in the food industry. It does have strong use cases for 3D plant-based technology but needs more advances to scale. Still, we have to factor in all of the known issues surrounding the 3D cell-cultivated meat movement such as slow speed, cell deformation and damage caused by shear stress, low cell viability, or cells loss of cellular, metabolic, or pluripotent traits (essential for actual 3D meat tissue formation), and lack of nanoscaffolding ability to make enhanced complex textures of meat with multiple different cell types and protein level complexity . The hardware component of these start-ups is easy to copy based on what we know in the world of regenerative medicine. Since extrusion 3D bioprinting was technically open-sourced technology by my first start-up in 2016 for $900  and by others in the RepRap 3D printer movement, there will soon be a surplus of copy-paste start-ups all using the same basic level extrusion 3D bioprinting technology.
Every month I see a new extrusion bioprinting company forming or a larger 3D printing company releasing some form of the basic technology. Rather than waiting another decade for the food industry to learn this information known in regenerative medicine, getting more advanced 3D/4D tissue engineering technologies and researchers with decades of experience into start-up mode within the alternative meat market is essential. The extrusion 3D bioprinting component does work well for plant-based meat, as demonstrated by OuroFoods pea-based protein POC, but again it’s too easy to copy and almost impossible to scale with one print head taking 20-30mins for 1 cm3. It was an easy starting point for the CTO of OuroFoods but in reality, the focus is on using advanced faster technology to enhance complexity. Especially when we are going into the realm of cell cultivated or hybrid meat with plant, cell, and fat tissue we need more advanced, faster, cell-protective, and nanoscaffold enabling 3D & 4D tissue engineering technologies are needed to create truly complex meat that can be scaled.
The media cost is the most significant barrier for a cultivated meat product to enter the market. Our mission at NouBio is to solve this problem and unleash the benefits of cultivated meat for all people at a reasonable price.Dr. Samad Ahadian, Founder and CEO of NouBio.
Despite being a lifelong meat-eater, I want an alternative that removes animals from the supply chain and maintains the taste of meat or fish. I don’t believe any human wants to see an animal harmed for food, and it will solve many of our current climate issues. Based on the existing standard, I think that the reality is that the only solution for the majority of the population is cell-cultivated or cell-based meat. Perhaps even a complex 3D hybrid that merges plant cells, fat tissue, and specific individual taste molecules or proteins, putting taste first. OuroFood’s vision, created by Dr. Elizabeth Bennett [CEO], Dr. Hakan Gurbuz [CTO], and chef Craig Dewar [CCO], is to create a complex hybrid of meat and fish, but with the primary goal of using advanced technologies to put taste first with novel R&D planned for taste molecules and individual proteins or emergence of the complex cell, plant and fat tissues in 3D.
OuroFoods is based in California but has a solid connection to the Netherlands, and the country that pioneered cultivated meat, via exclusive access to Ourobionics BV. The multiple disruptive patent-pending 3D bio-electric and multi-material microfluidic 4D tissue engineering technologies can transform the food industry too. The multiplexed 3D & 4D technologies are also patent-pending in creating cell-based and plant-based meat. They will be further patented for various use cases in multiple sub-sectors of the food industry. They are individually proven & published to be 30X faster than extrusion (one module), allow for animal cell, protein, and flavor molecule level bioencapsulation during the biofabrication process, & have a nanoscale resolution for enhanced complex meat scaffolding. They are fully scalable (1000X) for industry-level production while remaining cost-efficient.
The individual technologies have been proven within the regenerative medicine industry and created by the founders of Ourobionics. They are also being patented for multiple use cases in cell & plant-based meat production, allowing OuroFoods to disrupt the existing 3D meat industry and impact the technology needed to reduce costs or enhance efficiency in precision fermentation. The vision of OuroFoods is that it can start to impact multiple sub-sectors of food and even one day use the 4D biofabrication technologies to create self-assembling food, or food with edible biosensors to analyze health in the gut or our microbiome. This could have a positive impact on human longevity as we are what we eat.
These deep technologies [3D aerodynamic bio-jetting, 3D bio-electrospraying, 3D electrohydrodynamic jetting of cells, 3D cell-electrospinning] were first invented and proven for complex 3D tissue creation with hundreds of publications  by Prof. Suwan Jayasinghe at University College London (Founder of Ourobionics BV). During my Ph.D. at Imperial College London, these advanced bio-electric field technologies were merged and multiplexed with the different bioprinting hardware inventions I created from my tissue engineering research. Over the years, my unpublished research work involved technology such as bioreactors, 3D hollow fibers, alteration of pulsatile, steady and transmural flow in bioreactors, and other electric-field, bio-electric field and tissue engineering techniques (molds/decellularization), and it ultimately led me to 3D biofabrication machine building & multiplexing with Prof. Jayasinghes technology.
Most of my research work at Imperial College London (2011-2016) involved using pig (porcine) cells isolated from pig tissue. Hence, it is unpublished research data, close to a decade old, that can be used to advance the cell-cultivated and 3D-printed meat industry. When I met Prof. Jayasinghe during that time, he explained the advantages of newer, faster, advanced bio-electric field tissue engineering technologies with high viability and maintained the speed and nanoscale resolution of the electric field, merging them with 3D bioprinting hardware was essential. The unpublished patent-pending technologies that lead to the founding of Ourobionics BV are more advanced with new invention designs and exclusive to OuroFoods for advancing the food industry. The biofabrication & tissue engineering technology at OuroFoods are so disruptive that one module of the 3D bioelectric technologies is 30X faster (1cm3 in 1min, estimated 0.5kg/hr), with no cell damage or deformation, proven to encapsulate at protein or gene level (nm), has a nanoscale resolution for meat scaffold complexity, and potential to be scalable in future industrial machines (1000X) .
”Demand for animal protein is at an all-time high,” explained Aaron Chua; Founder & CEO of Fisheroo Ltd., “and with a growing population poised to reach 10B by 2050, there’s only 1-way protein demand is heading… upwards. And yet, conventional animal agriculture simply isn’t going to cut it moving forward, given its negative impacts on the environment and our health. Thus, this is exactly why alternative proteins like lab-grown cell cultivated meat/seafood are very much required as it is resource efficient and freed of contaminants, enabling us to continue enjoying the food that we have grown to love while being better for the planet and ourselves.”
All of these factors in existing 3D bioprinting, from the slow speed to cell damage and deformation, cells lacking traits needed to form complex tissues, and slow speeds of extrusion will impact the final meat tissue created, so we need to consider this when determining the real future for this 3D printing meat industry. Have we questioned how much can be achieved within any basic 3D printing hardware to mass produce 3D meat? Can the same be achieved by extruding cells and gels using a syringe by hand or in multi-layered molds that are then put into an incubator to grow? One company I am reminded of is Juiceroo where Google invested $120 million and found out the same could be done by hand. Additive manufacturing has stronger utility in other sectors and advanced technologies are more proven advantages in tissue engineering, but where does extrusion bioprinting lie when we compare 3D molds for meat to the process? The reality is that standard extrusion technology already takes 20-30 mins per print head for 1 cm3 of tissue, so if it can create 3D tissue, it lacks true scalability. If we focus on extrusion technology alone, we will need football fields full of machines to match the industry standard at a food production level. Sadly, a few extra extrusion syringes on a larger machine will not solve or scale the issues plaguing the entry-level hardware technology. That being said, extrusion technology does serve a purpose and will allow for fine-tuning of cells, biomaterials, ingredients, and other use cases for chocolates, pastes, and other standard 3D food structures.
That’s why new players such as OuroFoods have entered the market. They are going beyond the basic bioprinting technology with advanced 30-1000X faster nanoscale for enhanced complex meat scaffolding, animal cell & protein encapsulation . OuroFoods will disrupt the use of basic bioprinting technology in the meat industry with the advanced bio-electric and multi-material microfluidic tissue engineering technologies’ ability to scale 3D meat production 1000X. On top of this, technologies have been published to have no cell deformation or damage and potentially create detailed nanoscaffolding to merge meat cells, plant cells, fat cells, proteins, and taste molecules. The disruptive bio-electric field technologies have been individually published to keep the cellular, metabolic and pluripotent traits to make complex 3D tissues . The multiplexed technologies can go one step further to encapsulate at the protein, gene, or taste molecule level and could also impact and potentially enhance the precision fermentation of meat. The goal is to put taste first, with novel ideas merging advanced 3D tissue engineering technologies with the ability to create scalable complex meat and combine individual proteins and specific taste molecules.
One of the main issues for every company in this sector is not just the slow, limited basic hardware technology but the lack of serum-free alternatives or lower-cost media consumables to grow and create the meat. At present, serum-based media costs approximately $1,000 per liter. We are decades away from an affordable cell-based product on the shelves with or without advanced 3D/4D manufacturing technology. In parallel to cost, an additional reason to end fetal bovine serum is that it requires slaughtering pregnant cows. Enter NouBio, one of the companies I co-founded with Dr. Samad Ahadian [Founder and CEO of NouBio]. Samad has invented a cost-efficient and novel technology to create a serum-free media alternative that substantially drops bioreactor consumables’ cost. I can’t go into too many details. Still, the secret sauce of NouBio can potentially decrease the cost of media consumables for meat production bioreactors from $1000/liter for serum-based media by 95% while maintaining the final quality of cells and meat tissue formation.
NouBio’s media is powder-based, making it effective in supply chain management and global distribution. NouBio can already reach the desired price point the industry wants to achieve by 2030 and enhance the process of getting 3D cultivated meat onto the market. Since NouBio’s formation in late 2021, Samad and I have co-invented other patentable technologies to improve further serum-free media alternatives, nanoscaffolding for scalable meat growth structures, and other advanced bioreactor technologies. Samad has one key advantage in the industry as he was amongst the first tissue engineers in the regenerative medicine industry to create 3D muscle tissue with over 140 publications and has invented multiple different technologies that can advance cell-cultured meat to the next stage. Other companies such as Future FIelds and Integriculture are also working on alternatives. One core advantage of NouMedia and NouCarrier is not just the ability to drop the price point by 95%. At NouBio, there is no requirement for any FDA or USDA regulatory approval for NouMedia or NouCarrier, making it the perfect commercial solution for cultivated meat companies that want to drop the price point and maintain adequate production of 3D cell cultivated meat. Future Fields uses insects to create the serum-free media so it still requires FDA approval and harms animals. Similarly for Integriculture, they require the use of cells to make the replacement to FBS. Much more needs to be done to remove the complex and regulatory components.
Since I left academia in 2017, after a brief stint at the Massachusetts Institute of Technology (SMART campus, Singapore) under the supervision of the co-founder of the bioengineering department, Prof. Roger Kamm, I have never stopped inventing newer 3D/4D biofabrication technologies or encouraging new start-ups to build in multiple industries. All of these multiplexed technologies will benefit OuroFoods once Ourobionics further develop them. Some of these multiplexed technologies include the ability to 4D tissue engineer with added advantages of other technologies: acoustic levitation, magnetic levitation, ion-plume, decellularization, environmental biofabrication, & internal bioreactors. Most of my co-inventions, designs and prototypes since leaving academia in 2017 are still in very early stages of development, remain unpublished, and will require further testing for the creation of 3D cell-based tissues. However, they are being further co-developed and patented alongside the proven technologies of Ourobionics BV with younger highly skilled co-inventors Patrick Yopp (founder and CDO of Ourobionics; inventor of custom cryo-biofabrication print-bed in 2019) and Dr. Phillip Dettinger (Bioengineering Specialist, Post-Doc, & Entrepreneur). OuroFoods will have exclusive access to what we co-invent and improve within advanced deep technology at Ourobionics for the food industry. Then OuroFoods can work and co-develop the next generation of meat with many other innovators in this industry to take the biofabricated meat industry to the next level with newer technologies. One module of the bioelectric-field technology alone is 30X faster (1 cm3/min) compared to extrusion bioprinting, where one module takes 20-30minutes. OuroFoods can make a maximum of approximately 0.5kg/hr with one bio-electric field module, with industrial multiplexed machine designs that could scale this potential 1000X.
Meatable also recently showcased their cell-cultivated sausage, which looks almost identical to what we eat now, so I am very excited to taste it in the future. Maybe we don’t need to call cell-based or plant-based products meat? It could simply be a better choice on the menu—a new food with a new name. Even at OuroFoods, the team has discussed alternative branding such as souvlaki or gyros or terms that imply meat but do not directly state meat. As a non-vegan/vegetarian, I must be able to fool myself into meat’s complex taste and texture; it should be at a taste level where I cannot differentiate. The main risk in the industry is that some companies are rushing to create alternative meat products without focusing on the final taste. I will be honest in stating that I have tried almost every existing “meat alternative” on the Netherlands market, and I won’t be a repeat consumer due to the awful tastes and textures. Suppose all future companies rush to get products onto the market without maximized flavor and do the same as other companies. In that case, a meat-eating consumer like me might try the 3D cell-cultivated or 3D plant-based meat once and never eat it again. Almost all current vegetarian/vegan alternatives are highly processed, an issue I think 3D cultivated or hybrid meat and fish can solve. These are the main problems of existing vegetarian and vegan products. So companies must work together to put taste first to achieve the industry’s long-term vision and entirely remove animals from the supply chain. Advancements in 3D cultivated or plant-based meat might potentially solve a secondary problem in the industry where plastic is found within four-fifths of Dutch meat, creating a better version of meat.
I always remember back in 2013 discussing the potential of desktop 3D bioprinters with friends for food, and everyone always only really wanted to make 3D chocolate at home. I discussed the feasibility with a colleague with knowledge of the food industry. He questioned why do it when you can make it for cents using molding equipment and outsourced to Asia. We see more and more happening in that one generic sector with many companies such as Natural Machines Foodini dominating this market. Basic extrusion bioprinting technology, my first start-up open-sourced for $900 in 2016 ; more 3D printer companies are making similar bioprinters, and some are even reducing the cost of extrusion bioprinting technology to $300 (Chocol3D) . In my opinion, all extrusion 3D bioprinting should be that affordable in every sector and inside every home and lab. I have always had this crazy vision of Nespresso-style machines but have always fallen victim to too many ideas and only 24 hours a day.
I believe this is the realistic potential of extrusion-based bioprinters for food alongside some entry-level research and development into ingredients or components for plant-based or cell-based meat. True scalability is impossible with extrusion bioprinting technology, no matter how many print heads you add to an extrusion bioprinter based on the time it takes to print 1cm3. Not to mention the low cell viability, damage, or deformation of cells and proteins during the process and proven and published by independent research groups not connected to any start-up . Basic technology will always limit the creation of complex viable meat tissue structures or truly scalable meat at an affordable level. We don’t want to wait a decade for the food industry to learn from the mistakes of the regenerative medicine industry when basic 3D bioprinting is over-promised and underdelivered on 3D printed organs. We need to be realistic and focus more on the advanced 3D tissue engineering technologies like those at OuroFoods, MoojiMeats, Gelatex, Denovo Matrix and Matrix Food Technologies. Cellular Revolution has also worked on using tissue engineering technology to create a continuous process that enables more efficient and affordable cell production.
Regarding 3D-based meat, I believe that amazing things have been started in the 3D bioprinting sector from those at Redefine Meat, Meatech 3D & Nova Meat. It has a use case in making 3D plant-based meat with limitations on complexity and realistic scalability but for cell-cultivated meat more advanced faster tissue engineering is needed. If we want to deliver realistic scalability and truly complex meat tissue with all proteins, flavor molecules, and fat tissue interconnected, embedded together, and undamaged, we must invest more time and effort into advanced 3D tissue engineering and 4D biofabrication technologies. Gelatex uses electric field tissue engineering technologies that go one step beyond and can make 5kg/h of nanofibrous sheets for meat production, which is a remarkable feat . They have reduced the cost by 90% by using nanofibrous technologies; however, the main issue is that cells still need to be added to sheets after the process, like older tissue engineering processes.
Much is still unknown about Mooji Meats technology. However, it appears closer still linked to extrusion-based technologies known for cell and protein damage or deformation during the process. This one limiting factor of Gelatex technology is that if we want full complexity or hybrid structures of the cell and plant-based technology, the cells need to be incorporated into the process. They have 100% solved the speed component with their faster electric-field sheet generation technology. Still, it is missing the ability to add cellular, adipose (fat), and protein components in one instant before incubation and tissue formation. Matrix Food Technologies is another start-up focused on using advanced tissue engineering technologies for creating the scaffolding needed to add cells later in the process. The advantage the OuroFoods holds is that the patent-pending technologies can include cells, proteins, and taste molecules all at once in the same bio-electric tissue engineering 3D biofabrication of meat process where one module is individually proven 30X faster. The team at OuroFoods is already designing industrial-level machines that can become 1000X faster. This means the technology remains relatively affordable, but the ability to merge cells and proteins into the process enhances the complex textures and tastes that can be achieved.
Elizabeth from OuroFoods is also working in partnership with NouBio to ensure that the cell-based component is 1000X cheaper than existing serum-based media. OuroFoods is also open to working with any other company in the cell-cultivated or plant-based food industry. The proven ability, speed, and nanoscale resolution of the advanced 4D biofabrication and 3D tissue engineering technologies at OuroFoods can advance multiple stages of the product co-development with other industry leaders. Disruptive technologies can lead to various products with the complex structural and scalable merging of meat/fish, fat, plant cells, proteins, or flavor molecules. One area they are exploring with potential collaborators is within the mycelium meat sector based on the level that can be achieved with the patent-pending technologies (3D bio-encapsulation of mycoproteins or creation of custom 3D nanoscaffolding of substrates for fermentation and more). OuroFoods and NouBio both believe that this industry’s future depends on the co-development of advanced plant- and cell-based products with as many experts in the industry as possible. Why? The vision should constantly remove animals from the supply chain rather than profit or competition to be the best. We all strive for the same vision, many companies can attain profit, and the market is large enough for everyone to have a piece. Why compete when you can collaborate, disrupt, and empower others in the industry?
Something needs to change, convince other people like me to switch, and I believe we are on the cusp of that new reality. Even the famous chef quoted above was not the world’s biggest fan of existing vegetarian options. Countries like France and South Africa are slowly removing the ability to call it meat. We also do not know the long-term outcome of regulatory issues. To answer the question of the editorial, I believe that the reality is in the long-term potential of multiple advanced 3D tissue engineering, 4D biofabrication, biomaterial, cellular, and serum-free media technologies. In addition to this, I believe that partnerships with the pioneers of the industry are essential. The myth surrounding what exists now in the industry is that the basic technology cannot fully replicate meat’s complexity, taste, and texture. The cost of consumables to make meat is too high, and existing 3D plant-based alternatives are often highly processed and easy for other start-ups to replicate the basic 3D printing technology.
Finally, the myth predominantly focuses on the inability of “true scalability” in the 3D meat industry. It is the same story that was once told in regenerative medicine about the endless potential of extrusion 3D bioprinting. I fear someone will say that light-based technologies will be the future of meat even though they are always resin-based. We already have enough microplastics in our food; we don’t need food made from plastics. From a personal perspective of a person who started in this industry as an extrusion 3D bioprinting maximalist from the RepRap days of 2012/2013 and pioneer of the first wave in desktop 3D bioprinter start-ups, I would like us all to be realistic as we empower the next generation of bioengineers, innovators, and entrepreneurs in this highly innovative sector with the ability to disrupt the meat industry.
With that, I would like to end the editorial by repeating the quote from the famous chef on the most important aspect that food provides in our lives and why I believe we need to keep enhancing the future 3D biofabrication of meat technologies needed and inspiring others:
”Eat at a local restaurant tonight. Get the cream sauce. Have a cold pint at 4 o’clock in a mostly empty bar. Go somewhere you’ve never been. Listen to someone you think may have nothing in common with you. Order the steak rare. Eat an oyster. Have a negroni! Have two. Be open to a world where you may not understand or agree with the person next to you, but have a drink with them anyways. Eat slowly. Tip your server. Check in on your friends. Check in on yourself. Enjoy the ride.” Anthony Bourdain