The new “Big Three” of the 3D bioprinting industry

Similar to industrial additive manufacturing, the bioprinting business lives on excessive ups and downs. The ups deliver new enthusiasm and innovation, and the downs deliver again the fact of how complicated it’s for any new industrial section to emerge into an actual industrial alternative. On the identical time, the down durations usually conceal key traits that silently feed the following progress cycle, with new gamers rising as technological and market leaders. That’s roughly what has been occurring these days in bioprinting, with three key corporations, BICO, 3D Methods and Desktop Metallic (sure, Desktop Metallic, by way of the lately fashioned Desktop Well being division) rising as leaders, whilst dozens of smaller corporations and startups proceed to deliver innovation to the desk.

After we started to trace the 3D bioprinting market practically a decade in the past there have been lower than a dozen corporations working particularly on this section as industrial entities, with most improvement happening on the educational degree. Right this moment, 3dpbm’s 3D Printing Enterprise Listing’s Bioprinting part lists 133 entities, of which 47 are {hardware} (bioprinter) producers, 41 are materials (bioink) suppliers and 59 are thought-about service suppliers (a class that features bioprinting laboratories at universities).

This means a vibrant and energetic neighborhood, which nonetheless continues to be very a lot counting on college analysis and educational adoption, since industrial purposes of bioprinting stay restricted to early improvement and testing. These are at present meant as both cosmetics testing or drug improvement & testing (DDT). Manufacturing purposes, very similar to in most industrial 3D printing, stay a mirage principally as a consequence of challenges in phrases manufacturability (for organs and tissue grafts) and scalability (within the case of tissues and for the quickly  rising space of mobile agriculture/3D printed lab-grown meat purposes).

The Massive Three bioprinting corporations are every concentrating on these areas from completely different angles that they thought-about strategic.

Bioconvergence for industrial purposes

After some turmoil in mid-2022, as a result of tumbling inventory value and an inner feud between Co-founders Erik Gatenholm (CEO) and Gusten Danielsson (CFO), which led to the latter leaving the corporate, BICO is now once more trending upwards. The corporate has consolidated plenty of acquisitions performed over the previous couple of years and is now rising by concentrating on two foremost areas.

On the one facet, the corporate is concentrating on the enlargement of bioprinting analysis on the educational degree by way of its cost-effective CELLINK vary of bioprinters (and regularly evolving to extra superior methods in its provide), feeding it with a wider vary of bioink supplies (obtained from the acquisition of Superior BioMatrix).

On the opposite, BICO is working with superior applied sciences corresponding to these obtained by way of the acquisitions of Nanoscribe and, extra lately, Allegro 3D, in the direction of the event and implementation of business and scalable bioprinting purposes, beginning with tissue for cosmetics testing and evolving into organ analysis.

Given the change within the macroeconomic surroundings, we [BICO] have a agency concentrate on profitability and money moveErik Gatenholm, CEO, BICO

For the primary 9 months of 2022, this resulted in web gross sales of MSEK 1,565.4, about $ 150 million USD, which corresponds to a rise of 112 % in comparison with the corresponding interval through the earlier yr. In Q3 alone, BICO generated web gross sales of MSEK 550.6, about $30 million USD, which corresponds to a rise of 74 %, in comparison with the corresponding quarter earlier yr. CEO Erik Gatenholm mentioned that “Given the change within the macroeconomic surroundings, we [BICO] have a agency concentrate on profitability and money move.” The corporate additionally reported that natural progress amounted to twenty-eight%, (12% in fixed foreign money) and that “all enterprise areas reported double-digit natural progress in fixed foreign money”.

Since BICO is the one public bioprinting (nearly) pure participant (after Organovo collapsed and exited the section), its public monetary outcomes and publicly disclosed methods are a very good indicator of bioprinting’s general well being. BICO’s long-term and mid-term objectives are to scale back the organ scarcity and pace up drug improvement by offering accessible life science options that mix biology and know-how. The idea of bioconvergence, which impressed the corporate’s identify, refers to utilizing a mixture of robotics, synthetic intelligence, superior genomics, and 3D bioprinting, to create new healthcare options.

When contemplating all the businesses that at the moment are a part of the BICO group, there are as many as 11,000 devices within the area, with most of those being bioprinters of assorted sorts (together with 3D printers used for scaffolding in mobile cultures). Beneath bioconvergence, the traces between biology, engineering, nanotech, and information change into more and more blurred, permitting synergies to strategy to biology as extremely superior engineering that’s been refined over billions of years. Inside bioconvergence, Biosciences, present user-friendly devices to deliver effectivity and pace to a number of software areas, corresponding to cell line improvement, drug screening, and microscopy. Bioautomation accelerates the event and manufacturing of diagnostic and bioanalysis check platforms for sufferers, shoppers, public well being and the surroundings. Lastly, Bioprinting allows printing with cells and biomaterials, creating tissues and organ-like buildings that mimic physiological circumstances.

BICO’s mission is to allow the pharmaceutical and biopharma industries to develop new medicine quicker and safer, with extra specificity and fewer want for animal testing. The corporate’s technique till lately has been to amass progressive know-how corporations as soon as they’re de-risked and prepared for commercialization and scaling up. After some challenges, the group now appears well-positioned for speedy progress, as a number one supplier of drug discovery and drug improvement instruments. It is a comparable technique to the one pursued by Organovo, with failing outcomes. Nevertheless, BICO is working at an already a lot bigger degree by way of revenues and accessible applied sciences, with extra cost-efficient and accessible instruments that are already producing vital returns. Organovo was a pioneer however it might have entered the bioprinting market too early.

BICO’s acquisition section was very speedy (over a interval of nearly 2 years), and the result’s a extremely diversified product providing, which limits technical dangers. In a number of circumstances, these applied sciences basically change the best way laboratories work, implementing new and environment friendly workflows to automate operations. Many of those options are the outcomes of synergistic work from a number of of BICO’s corporations working cooperatively. Examples embody customizable MatTek Dishes mixed with the ECHO Revolve hybrid microscope for simple to make use of, common compatibility with laboratory tools, built-in glass coverslip for ultraclear imaging, no messy or fragile slides, and customised choices to go well with cell tradition and/or imaging aims. One other is the G.STATION NGS, developed in collaboration between Dispendix, Cytena and Qinstruments to supply automated workflows for next-generation sequencing. Lastly, Bionova, the primary digital mild processing (DLP) primarily based bioprinter for direct printing in multi-well plates, combines applied sciences from Allegro 3D, Cellink and Superior BioMatrix. It prints practical tissue fashions in seconds with superior decision, pace and reproducibility. It additionally accelerates analysis by offering biomimetic fashions for regenerative drugs, precision drugs and illness modeling.

BICO administration is now bullish about medium and long-term prospects highlighting alternatives throughout all three enterprise areas. The principle driver is recognized in large pharma’s transfer in the direction of laboratory automation processes. Right here Biosero’s Inexperienced Button Go platform is changing into a typical in lab automation. It gives user-friendly accessible approaches to automating guide processes with accuracy and cost-efficiency. The FDA Modernization Act 2.0 within the US, whether it is lastly enacted, would enable pharma corporations making use of for market approval for a brand new drug to make use of strategies apart from animal testing to determine the drug’s security and effectiveness. Considerably for BICO, these various strategies could embody cell-based assays, organ chips and microphysiological methods, pc modeling, and different human biology-based check strategies. What this implies for the pharma and beauty industries is that animal fashions can be phased out over time, and the business will get higher outcomes with human fashions. BICO’s vary of services and products within the tissue engineering enviornment is supposed as a one-stop store that may match prospects in numerous phases of improvement.

Placing the AM into bioprinting

3D Methods formally entered the bioprinting section by buying startup firm Allevi, which tried to do one thing just like CELLINK (in reality it was one of many very first to launch a low-cost bioprinter) however with much less efficient outcomes. As an alternative of ranging from supplies to progressively broaden into {hardware}, like CELLINK, Allevi (which on the time was referred to as BioBots), began from the {hardware} and had a tougher time in establishing a major put in base. The corporate went by way of some modifications in administration, together with the identify change to Allevi, and was lastly acquired by 3D Methods in Could 2021, making it into one of many foundations to its new bioprinting enterprise.

Right this moment Allevi will be thought-about a number one innovator within the bioprinting area with an unique concentrate on the analysis and improvement neighborhood. Main laboratories leverage Allevi’s portfolio of {hardware}, biomaterials and software program to design, engineer and construct options for tissue engineering, organ-on-a-chip analysis, pharmaceutical validation, biomaterial improvement, and regenerative drugs.

Right this moment – at this time limit – we are able to take this step in regenerative drugs to affect the way forward for mankind.Chuck Hull, Founding father of 3D Methods and inventor of 3D printing (stereolithography).

On the time of the acquisition, Chuck Hull, Co-founder of 3D Methods and inventor of 3D printing (stereolithography), who has taken a eager curiosity within the firm’s transfer in the direction of bioprinting, commented by saying that “Right this moment – at this time limit – we are able to take this step in regenerative drugs to affect the way forward for mankind.”

For greater than three a long time, 3D Methods created new approaches and processes for product improvement, components manufacturing and personalised healthcare by way of additive manufacturing options. The corporate owns patents for a number of completely different additive manufacturing applied sciences, together with metallic and polymer processes used within the orthodontic and orthopedic implant industries – which share a number of elements with bioprinting processes and purposes.

The corporate is now trying to implement a holistic strategy, leveraging this expertise to innovate bioprinting applied sciences and rework affected person care. By enabling the fabrication of residing tissues, 3D Methods seems to be at bioprinting as a way to push the boundaries of regenerative drugs, disrupting healthcare as we all know it.

Recognizing that the analysis neighborhood is crucial to growing breakthrough improvements in regenerative drugs, 3D Methods started by specializing in Analysis and Improvement, with the addition of Allevi in Could 2021, offering a set of bioprinting options to each researchers and pharmaceutical business giants in tons of of labs globally.

Allevi’s latest desktop 3D bioprinters are versatile and straightforward to make use of, giving customers entry to a variety of biomaterials—bioinks, bioink components, cells, reagents and consumables—in addition to an intuitive software program interface.

The following step in 3D Methods’ bioprinting technique focuses on the corporate’s extensive expertise within the medical units and implant segments. Thus far the corporate produced greater than 2,000,000 serial element medical units and 140,000 patient-specific surgical circumstances: now it’s trying to scale the manufacturing of bioprinted scientific purposes, leveraging and adapting present know-how (which might nearly seamlessly be used for scaffolding) to raise affected person care by way of varied scientific purposes, starting from acellular bioresorbable units to functionalized stable organs for transplantation.

Along with United Therapeutics Company and its organ manufacturing and transplantation-focused subsidiary, Lung Biotechnology PBC, 3D Methods achieved important progress within the improvement of next-generation bioprinting options for lung scaffolds which are able to full-size, vascularized, speedy, micron-level printing.

3D Methods’ capabilities as a know-how innovator, spanning {hardware}, software program, and supplies science, mixed with United Therapeutics’ famend experience in regenerative drugs has enabled advances in lung modeling, 3D printing, in addition to materials formulation and materials dealing with to yield important capabilities in bioprinters and biomaterials for the eventual manufacturing of transplantable organs.

The pure evolution of this facet of 3D Methods’ technique is to implement superior bioprinting know-how improvement to satisfy the evolving wants of the scientific and R&D communities. Right here, the trademarked Print to Perfusion course of allows 3D printing of high-resolution scaffolds, which will be perfused with residing cells to create tissues.

The flexibility to print massive, vascularized, extremely detailed hydrogel scaffolds at speedy speeds is opening new alternatives for a spread of tissue purposes. As well as, 3D Methods is growing bioprinting options which are each commercially viable and scalable from prototype to manufacturing.

The ultimate ingredient in 3D Methods’ bioprinting technique is to develop extra complicated organic buildings and tissue engineering. That is the place the acquisition of Volumetric Biotechnologies introduced on important tissue engineering experience to broaden the scope of human organ bioprinting efforts. The businesses at the moment are establishing a analysis facility in Houston, Texas to speed up the event and commercialization of vascularized human tissues and bioprinted constructs for non-organ purposes, and creating clear technological management within the quickly rising bioprinting area for laboratory purposes together with drug discovery.

Extra present collaborations, with CollPlant Biotechnologies and Antleron, additionally broaden the capabilities in regenerative drugs analysis and improvement options, as 3D Methods continues to hunt companions with the identical mission of reworking healthcare by way of groundbreaking applied sciences.

Not too long ago 3D Methods additionally launched Systemic Bio, a completely owned firm primarily based in Houston, Texas, targeted on the event of vascularized organ fashions made out of hydrogels and human cells for use for drug discovery and improvement. With a state-of-the-art laboratory and a workforce of bioengineering specialists, Systemic Bio is pushing the boundaries of preclinical drug testing. Its proprietary platform is constructed with production-level 3D Methods know-how, which has a better construct quantity and a better decision than most commercially accessible applied sciences.

When it comes to monetary outlook, 3D System’s bioprinting-related actions don’t but signify a major income era section nonetheless they’re thought-about extremely strategic. In its newest Q3 monetary outcomes, the corporate acknowledged that “new alternatives for large-scale adoption of additive manufacturing opening earlier than us, and completely new markets being created in bioprinting, we imagine we’re very effectively positioned to ship on our dedication to change into a $1 billion income firm in 5 years.”

Embracing the previous and way forward for bioprinting

Understanding how and why Desktop Metallic just isn’t solely instantly concerned but additionally one of many leaders of the bioprinting market is a little more difficult, with out first reviewing the corporate’s current general progress technique. Desktop Metallic’s current acquisitions make its bioprinting strategy a hybrid between BICO’s and 3D Methods’, with the Boston-based firm qualifying as each a brand new entry and a conventional additive manufacturing market chief.

Desktop Metallic was based in late 2015 with the acknowledged goal of constructing metallic additive manufacturing each extra accessible (at first, by way of a sure metallic extrusion course of) and extra scalable (by way of a metallic binder jetting course of). Six years later, these aims haven’t but been achieved however they’re so much nearer. Extra importantly, many extra purchased into Desktop Metallic’s imaginative and prescient together with rivals, prospects and – most significantly – buyers, with the corporate elevating over $2 billion after going public by way of a SPAC merger in late 2020.

These funds had been utilized by the corporate’s founders to each develop its personal proprietary applied sciences and purchase two conventional additive manufacturing market leaders and pioneers: ExOne, a specialist in ceramic, sand and metallic additive manufacturing by way of binder jetting, and ETEC (previously EnvisionTEC), the pioneer and chief in digital mild projection (DLP) stereolithography know-how, which is closely used within the dental business. ETEC additionally included one other key know-how, which it refers to as its 3D-Bioplotter enterprise. All of ETEC’s dental enterprise and the 3D-Bioplotter enterprise have now been built-in right into a division referred to as Desktop Well being.

I personally discover it fascinating seeing what researchers will do with it subsequentCarlos Carvalho, Staff Chief Bioprinting Staff at EnvisionTEC (now ETEC)

Though it was by no means supported by aggressive advertising (that’s now more likely to change, as highly effective advertising is on the coronary heart of Desktop Metallic’s technique), the 3D-Bioplotter has been the reference for high-end bioprinting analysis for over twenty years, because the platform was launched within the yr 2000. Right this moment there are three 3D-Bioplotter fashions in the marketplace: Starter, Developer and Producer. Many machine options fluctuate between fashions. For instance, the Producer mannequin permits for five print heads and in addition features a heated platform and sterile filter, which is advisable for cell printing.

“I personally discover it fascinating seeing what researchers will do with it subsequent,” mentioned Carlos Carvalho, Staff Chief Bioprinting Staff at EnvisionTEC (now ETEC). He led the event of the fourth era of the 3D-Bioplotter and has labored on the bioprinter since its infancy on the College of Freiburg in Germany. The EnvisionTEC bioprinter has additionally been used to manufacture components utilizing graphene, hyperelastic bone inks, ovary implants, a placenta mannequin and is being utilized in bone regeneration analysis.

The 3D-Bioplotter bioprinters can course of open-source biomaterials utilizing air or mechanical stress to a syringe, which might fabricate scaffolds to create tissue, with X-Y repeatability right down to 1 μm. All fashions have been designed to be used in a sterile biosafety cupboard, meet requirements for scientific trials and provide construct sizes as much as 192.4 cubic inches.

The system makes use of modular elements, corresponding to sterilized heating and cooling cartridges, normal Luer-Lok syringes with normal needle-tip sizes and an easy-to-use 365 nm UV curing head. “It’s a preferred device as a result of it’s a really versatile, but additionally user-friendly machine,” Carlos defined. The software program additionally permits for optimum freedom in combining completely different supplies utilizing completely different temperatures.

Desktop Well being’s bioprinting and normal healthcare technique recognized 5 completely different ranges. The primary is Drug Discovery, which incorporates mimicking pathologic tissue (for efficacy), and wholesome tissue (for security), concentrating on a excessive throughput. That is thought-about a well-established section of bioprinting. The following two ranges signify the corporate’s present focus and are thought-about to be inside attain. Customized Implants & Grafts (degree 2) consult with therapies for backbone fusion, non-union fractures, craniomaxillofacial, nerve conduits, tendons, ligaments, and bones. Tissue (degree 3) refers back to the bioprinting of breast, pores and skin, cornea, bones, cartilage, and coronary heart valves

The ultimate two ranges signify the long-term purpose of Desktop Well being’s technique and of bioprinting on the whole. They embody Endocrine Glands (degree 4), which is the power to supply a whole ovary, pancreas, thyroid for testing and ultimately for implantation, and Organs (degree 5), which embody the power to supply practical lungs, kidneys, livers, and hearts.

All these are primarily based on the event and introduction of each bioprinting-specific supplies and normal healthcare 3D printing supplies. The 3D-Bioplotter platform makes use of Hydrogels & Cells designed to be each biocompatible and cell-friendly, able to supporting quite a lot of purposes in bone regeneration, cartilage regeneration, gentle tissue fabrication, drug launch, and organ 3D printing. Different 3D-Bioplotter supported supplies embody Ceramics, which is bio-active, osteoinductive and osteoconductive supplies which are designed to advertise bone progress within the implantation space. These are utilized in crucial measurement defects as bone grafts with complicated internal patterns that mimic the encompassing bone’s mechanical properties, and as customized ceramic implants in maxillofacial purposes. The general healthcare technique additionally consists of Photopolymers (for speedy medical gadget fabrication), Metals (for surgical instruments, prosthetics, splints and implants) and Thermoplastics (for cartilage regeneration purposes, corresponding to knee meniscus or trachea defects).