Just like in any segment of additive manufacturing (polymers, metals, ceramics, composites), the market for bioprinting inks—or bioinks—is the key element to understanding, determining and assessing the evolution of the entire segment. Bioprinting hardware technologies are now more established and the development of viable bioprinting applications is now dependent on the availability of new bioink materials and the bioink manufacturers that market them.
As further proof of this, the rapid rise of Cellink (now BICO) to bioprinting market leadership started from the commercialization of the first bioink products specifically targeting low-cost, open-source bioprinters. And that same growth has been strengthened by the acquisition of Advanced Biomatrix, the leader among bioink manufacturers for its bioprinting-specific materials. Today more companies are offering bioinks than ever before and following in BICO’s footsteps.
Here we present some of the most interesting companies (and their products) among the 40 companies currently listed in 3dpbm’s 3D Printing Business Directory’s dedicated Bioink Manufacturers section.
Advanced BioMatrix (acquired by BICO)
Advanced BioMatrix is a leader in the life science of 3D applications for tissue culture, cell assay, bioprinting and cell proliferation. The company, which was recently acquired and became part of the BICO Group, can be considered one of the market leading bioink manufacturers, with an almost unrivaled selection of products.
The company is located in the San Diego region—one of the world’s largest life science and biotechnology clusters—and has been manufacturing and delivering high-quality products for research uses and applications for over 10 years. Today its offer includes expertise in production, isolation, purification, lyophilization, cell culture and testing of proteins, adhesion peptides, attachment factors, bioinks, substrate rigidity and other 3D matrix products.
As per the company vision of “Transforming science to a new level of discovery by providing advanced technologies through innovative 3D matrix products”, Advanced BIoMatrix has continued to add several new products each year that provide research tools for customers worldwide, developing new products and technologies within the company and collaborating with many research institutes, universities and life science companies.
Bioink is sold under the Lifeink brand. The main expertise at Advanced BioMatrix is with extrusion-based bioprinting, though many products, including methacrylated collagen, methacrylated gelatin, methacrylated hyaluronic acid and thiolated hyaluronic acid have been used in publications across several different bioprinting methods. Advanced Biomatrix also developed the FRESH method for bioprinting. FRESH stands for Freeform Reversible Embedding of Suspended Hydrogels. The technology utilizes a gelatin support bath, or slurry, that essentially traps the construct in place as it’s printed inside the slurry. In order to print native extracellular matrix proteins without the use of added non-native materials (such as cellulose or alginate), a support material is required. Natural proteins lack rapid crosslinking or structural integrity for vertical 3D printing, without support.
LifeSupport is the official ready-to-use gelatin support slurry for FRESH bioprinting and has been used to print constructs such as nasal cartilage, a meniscus, heart valves and even an entire heart—out of native ECM proteins.
CollPlant is a regenerative and aesthetic medicine company developing innovative technologies and products for tissue regeneration and organ manufacturing. The company’s plant-based technology is the only commercially viable technology for mass production of recombinant human Type I collagen (rhCollagen), which is identical to the collagen produced by the human body. This makes CollPlant’s rhCollagen the ideal building block for regenerative medicine. Leveraging on the unique properties of rhCollagen and biomaterial know-how, CollPlant is now developing a pipeline of products aimed at 3D bioprinting of tissues and organs and medical aesthetics.
Collink.3D by CollPlant is the first and only human collagen bioink platform, based on plant-derived recombinant human type I Collagen (rhCollagen), allowing for perfect mimicry of native tissue or organ properties. It enables the scalable and reproducible biofabrication of scaffolds, tissues and organs for 3D modeling and transplantation.
Biofabricated constructs using Collink.3D offer improved biological performance, consistency and safety, and can be used in a variety of applications including drug discovery, drug screening and tissue testing, as well as the development and manufacture of transplantable tissues, scaffolds and organs. Collink.3D is compatible with major 3D bioprinting technologies and cell types.
Jellagen is a UK company that was founded in 2015 by Professor Andrew Mearns Spragg, a Scottish marine biotechnology pioneer. Among bioink manufacturers, Jellagen stands out as a marine biotechnology company, manufacturing Collagen type 0 bioinks for medical and scientific research applications and using its proprietary technology to produce it from jellyfish and market it under the JellaGel brand.
Collagen type 0 is an evolutionary ancient stem collagen that is foundational, allowing greater applications across multiple indications. Unlike alternative collagens which are more specific therefore restricting their end applications, Collagen Type 0 is more versatile due to its evolutionary lineage. For this reason, it can be classed as the “stem of all collagens”.
JellaGel is made from Jellyfish collagen, which is categorized as collagen type 0 due to its homogeneity to the mammalian types I, II, III, V and IX. It is suitable for in vitro cell culture and tissue engineering, offering a natural, non-mammalian alternative to mammalian and synthetic hydrogels that are currently on the market. One of the defining features of JellaGel is that it can be used at room temperature meaning there is no need for ice or cold rooms, unlike some hydrogels currently on the market. This product is supplied in kit format with JellaGel solution, buffer and crosslinker for ease of use.
Rousselot is the world’s leading collagen supplier. The UK company produces many different gelatin- and collagen-based products for industries and consumers around the world.
As the leading collagen supplier, Rousselot stands out among bioink manufacturers, for its high-quality collagen and gelatin-based bioinks specifically for bioprinting. The X-Pure low-endotoxin pharmaceutical-grade modified and non-modified gelatins are available as bioinks and can be used to generate customized organs-on-a-chip for drug development, engineer new bone formation, or printing of cell-laden scaffolds. The X-Pure GelMA is an ideal scaffold or carrier biomaterial, mimicking the extracellular matrix. It has excellent thermostability at 37°C and can help create a perfect environment for cell growth. It is also the first GMP-ready gelatin methacryloyl bioink.
Rousselot also recently introduced the X-Pure GelDAT bioink, which is functionally equivalent to the GMP-grade material, so researchers have less risk of having to re-validate their biomaterial prior to clinical trials. X-Pure GelDAT is a unique addition to the Rousselot portfolio because of its phenolic modification that grants superior adhesion properties to human tissues and because it can be cross-linked by both enzymatic reaction or photo-induction. These characteristics allow its combination with other biomaterials for the creation of more versatile and complex structures for drug delivery, tissue engineering, organ-on-a-chip and complex wound dressing applications.
Humabiologics is the first company to introduce native human collagen bioinks and gelatin bioinks. These bioinks enable researchers to advance the translational research of bioprinted human organs and tissues. The company was founded by current CEO Mohammad Albanna, leveraging extensive experience in the field of Tissue Engineering and Regenerative Medicine (as Adjunct Professor of General Surgery at the Wake Forest University School of Medicine).
Leveraging proprietary processes to manufacture its products, Humabiologics partners with FDA-registered and accredited tissue banks around the US to utilize thoroughly screened donated human tissue that will not be used for transplant. Its bioink product offering includes native human collagen, bone gelatin and extracellular matrix. These human-derived products are designed to address several ongoing challenges.
For example, most of the current sources of collagen and gelatin marketed by bioink manufacturers come from animal tissue such as skin, bone, tendons, and ligaments from cows, pigs, rats and fish. While there are some similarities between human and animal collagen, minor variations in collagen composition can result in significant differences in the properties of collagen and impact the cellular response and the formation of tissue. The use of animal products in research can lead to poor translation aspects, irrelevant outcomes, and potential FDA regulatory hurdles that can slow the development of life science innovations.
The successful use of the first native human collagen bioink was published by Vipuil Kishore’s team at Florida Institute of Technology (FIT) in a paper titled “In vitro characterization of xeno-free clinically relevant human collagen and its applicability in cell-laden 3D bioprinting”. The authors used lyophilized human collagen derived from human skin. They were able to create several formulas of bioinks. The advantage of using lyophilized collagen provided researchers with the ability to tailor the properties of collagen to meet their specific therapy needs. The paper demonstrated the successful use of human collagen to print stable structures using bone cancer cells, which was not possible with animal collagen unless higher concentration or further processing of collagen is employed. The paper also showed structural differences between human and animal collagen. The results provided an impetus for using human-derived collagen as a viable alternative to animal collagen sources for 3D bioprinting.
4D Biomaterials is the trading name of 4D Medicine Ltd, a company that was spun out from the Universities of Birmingham and Warwick in April 2020. Among the companies listed here, it is the only one to commercialize a new class of materials: liquid resins that can be printed into solid 3D scaffold implants to help patients recover from major medical procedures.
The polycarbonate-urethane-based resins, marketed under the trade name 4Degra, are novel bioresorbable materials with good shape memory, tuneable mechanical and chemical properties and promising tissue-healing performance. The composition of the resins is protected by a family of patents owned by the company.
4Degra resin-inks are available in Technical Grades’ (T series) for use in research and development projects. By tuning the chemistry and formulation of the 4Degra resins it is possible to achieve a wide range of physical properties, shape memory behavior and degradation-time profiles in the finished 3D printed parts made from them.
The company’s standardized product range includes ‘soft’ T15 and ‘hard’ T800 variants with tensile elastic moduli of 15 Mpa and 800 Mpa respectively. Higher modulus grades are also under development.
4Degra resin-inks show some advantages over the next-best alternatives in numerous biomedical applications. The ability to 3D print complex scaffold designs and other implantable medical devices with fine resolution (down to 5 microns in the Z axis, and 2 microns in the X and Y axes) and shape memory functionality, offers collaborators broad product development potential.
In partnership with business partners from the 3D printing and medical device sectors, the company is developing target product concepts for a range of indications, ranging from implantable micro-devices to tibial fracture repair devices.
Part of the €8.6 billion UPM Group, UPM Biomedicals is the forerunner in producing high-quality nanofibrillar cellulose for medical and life science applications. More than 300 patents protect the existing and future products that rely on the Finnish birch pulp. The company actively collaborates with universities, research centers and key industrial partners on future innovations and products in the field of high-throughput drug screening, personalized medicine, advanced cell therapies, 3D bioprinting, tissue engineering and advanced wound care.
UPM’s GrowInk Bioinks for 3D bioprinting are animal-free, biocompatible, ready-to-use hydrogels that can be mixed directly with cells for bioprinting applications. The two main components in GrowInks are nanofibrillar cellulose and water, providing a fully defined matrix. The matrix can be customized by the addition of molecules, such as growth factors or adhesion proteins, as needed by your specific cells.
Available in various versions, GrowInks mimic the in vivo environment supporting cell growth and differentiation. Over 150 different cell types have been cultured in nanofibrillar cellulose. They can easily be diluted to provide a wide range of stiffnesses that can be matched to the requirements of your cells. GrowInks are room temperature stable and can be used with or without a crosslinking agent depending on your application, but all enable cell printing layer-by-layer with high-precision cell positioning.
INNOREGEN is attracting attention among bioink manufacturers from the regenerative medicine industry for its first commercial functional bioinks. As the first company in Korea to work on developing bioinks that combine human-derived collagen/human-derived extracellular matrices with hydrogels, INNOREGEN supplies tissues with living cells customized to numerous researchers in the relevant fields.
These include Gel4Cell,Gel4Cell-BMP, Gel4Cell-VEGF, Gel4cell-TGF, Col4Cell, etc., providing the optimal environment for making living cells torealize the dream of artificial organs. Bioinks can also be custom produced for a speecific research purpose, research field, and research subject. After selecting a bioink suitable for the research field andanatomical part and receiving the cells, INNOREGEN can print andsupply the tissues required by any researcher.
Axolotl Biosciences was founded in Victoria, BC in 2020 by Dr. Stephanie Willerth, Dr. Laura De la Vega, and Laila Abelseth. A spin-off of the internationally recognized bio-printing-focused research group lead by Dr. Willerth at the University of Victoria, Axolotl was born from the demand for innovative bioinks by academic researchers and biotechnology companies alike. The company stands out among bioink manufacturers for its focus on the biological needs of cells in 3D bioprinted constructs, for which it created a novel bioink capable of printing hiPSC-derived neural cells that maintain high levels of cell viability for over a month.
The company provides turn-key reagents, including bioinks, 3D tissue models, and consulting services in the field of 3D bioprinting to advance the field of tissue engineering and regenerative medicine. Its goal is to deliver products that enable the 3D bioprinting of humanized tissue models for advancing medicine.
Axolotl’s TissuePrint Low Viscosity (LV) bioink is optimized for use on microfluidic bioprinters such as the Aspect RX1 by Aspect Biosystems. Its TissuePrint High Viscosity (HV) is optimized for use on extrusion-based bioprinters such as the BIOX by Cellink. Its TissuePrint Crosslinker is a research-grade, xeno-free crosslinker that pairs with both our High Viscosity and Low Viscosity TissuePrint Bioinks. Crosslinker is used alongside the bioink in the bioprinting process to create the printable fibers used to build 3D constructs.
Founded in 2019, Akira Science is an interesting startup on a mission to remove the barriers for soft tissue engineering via polymer scaffolding. The company’s breakthrough innovation, the AKIMed c12 filament/scaffold, makes soft tissue regeneration smarter and easier. It is non-toxic, degradable, biocompatible, pliable, 3D printing-compatible and offers a uniquely affordable solution among various bioink manufacturers in the market.
AkiMed-c12 is a unique material alternative for tissue engineering offering a controllable degradation profile and negligible thermal degradation. The filaments are made from the proprietary Akimed- c12 polymer which is synthesized in Akira’s lab and then extruded to ensure high quality for research applications. The filament or pellets can be used for fabricating scaffolds through fused filament fabrication (FFF) of a material that is similar to poly (ɛ-caprolactone), PCL, but has a more rapid degradation behavior. It is intended to be used to manufacture soft and pliable scaffolds while offering a well-characterized polymer to the scientific community.
This article is an updated version of the article that first appeared on 3dpbm’s AM Focus Bioprinting eBook that we released in March 2022. View or download the entire issue, available here.