3D Bioprinting for Regenerative Medicine : Part 1

A quick search in Pubmed on keywords “stem cells”, “tissue engineering”, “regenerative medicine”, and “bioprinting”, gives a single shot at the history of this fascinating field. (Figure 1) The earliest publications shown on these subjects were in 1911 (“stem cells”), 1920 (“regenerative medicine”), 1942 (“tissue engineering”), and 2000 (“bioprinting”). More observant readers may notice that a more significant increase has taken place only after the 1950s for “stem cells”, the 1980s for “regenerative medicine” “tissue engineering”, and “bioprinting” only slightly more than a decade ago. Meanwhile, 3D printing (or “additive manufacturing”) was invented in the 1960s, and commercialized in the 1980s; personal computing started to take off in the 1980s; the internet was invented in the 1990s. While the official counts of all publications may not be accurate based on Pubmed alone, this brief history does tell a story of the effects of technological advancements and confluence on changing our capacity to create and on the evolution of our belief systems on what is possible to live longer and better. There is a parallel storyline in the entrepreneurial and commercialization space. This is reflected by a quick patent search (Figure 2) and venture-backed bioprinting startups (Figure 3) in the last several years. Concurrently, an important global regulatory trend against animal testing and products is another force accelerating alternatives in drug developments, many of which are related to the field of regenerative medicine [1-3]. In this article, we will focus on one more recent confluence: how 3D bioprinting is changing the regenerative medicine landscape. 

Figure 1. Bioprinting and 3D printing are relative newcomers compared to other biotechnologies based on a quick Pubmed Keyword search.

More specifically, we will discuss the following in two separate blogs.

Part I: 

  • What is regenerative medicine?
  • What is 3D bioprinting?
  • Why are people using 3D bioprinting in regenerative medicine? 
  • Which organ systems or applications are making progress?
    • Bone
    • Cartilage
    • Muscle
    • Nervous system
    • Lymphatic system
    • Integument
    • Circulatory system
    • Endocrine system
    • Respiratory system
    • Urological system
    • Digestive system
    • Eye

 Part II: 

  • What is the ecosystem like in this space? 
  • What are some of the ongoing challenges? 
  • Who are the most influential academic voices right now? 
  • Which companies are the most influential in this space? 
  • Which supportive technologies (other than bioprinting) are most relevant to the field? 
  • What are some existing competing technologies?
  • What is on the horizon?

What is regenerative medicine? 

Regenerative medicine differentiates itself from traditional disease management in that it aims to accelerate the healing process both structurally and functionally with a set of engineered conditions. While the human body is equipped with its own natural repair mechanisms for some conditions, for example, a simple knife cut to the skin. The body cannot heal many acute, chronic, and degenerative diseases.

We obviously cannot grow back a lost limb naturally like an axolotl. We also mostly cannot heal damaged cartilage and the nervous system, which play big parts in the aging process. In addition, not all healing processes deliver the best results. For example, debilitating scarring after a major burn injury. Regenerative medicine aims to leverage new technologies to promote and improve that healing process.

The concept of regenerating parts of the body can be traced back to the 700s BC by the ancient Greeks [5], even though the first Pubmed study was published in the 1920s.

Over time, modern medicine has developed transplantation to directly replace damaged or missing organs, cell therapies, immunomodulation therapy to induce regeneration, and tissue engineering for a variety of regenerative applications ranging from drug development to tissue replacements. [5] These technologies are all included in the much broader concept of “regenerative medicine”. With the intention of not just “managing” disease but fully “restoring” normal health, regenerative medicine also broadly includes gene therapy, genomic medicine, personalized medicine, biomechanical prosthetics, recombinant proteins, and antibody treatments. Therefore, the field of regenerative medicine significantly overlaps with many end applications of 3D printing, tissue engineering, and 3D bioprinting.  

What is 3D bioprinting?

While regenerative medicine is not all about engineering, biomedical engineering is playing an increasingly important role. In simpler terms, tissue engineering is a branch of biomedical engineering dealing specifically with the combination of biomaterials, cells, and biochemical factors to support or replace endogenous tissue [4]. 3D bioprinting is a branch of tissue engineering that it allows for the precise deposition of these critical components digitally in order to achieve the tissue engineering goal. [Figure 4] Bioprinting has the potential to create precise, complex, multi-material, multi-cellular structures at a scale that simulates nature that no other existing techniques can. In addition to creating complex microstructures directly with cell-embedded bio-inks, bioprinting can also produce microscale biocompatible medical devices such as microfluidics, which is an industry of its own. 

While technology is still very new, labor intensive, unreliable, and in most cases, under-delivering in end applications, it is encouraging that the field has advanced significantly in both academia and commercial space in the past two decades. This advancement is a combination of advancements in 3D bioprinting processes, new biomaterials and bio inks, stem cell technologies, and end application development. We have written blogs and hosted events on all of these subjects in the past:

Stem Cell Considerations for Bioprinting or Tissue Engineering

3D Bioprinting Substrate Stiffness – Often Overlooked, But Always at Work

3D Bioprinting Glioblastoma Models for Drug Screening

3D Bioprinting Bone – One Defect At A Time

3D Bioprinting: The Yellow Brick Road of (Part 1) (Four-part series by Andrew Hudson from Fluidform3D)

The Yellow Brick Road of 3D Bioprinting (Part 2): Soft Is Hard

3D Bioprinting Substrate Stiffness – Often Overlooked, But Always at Work

Why are people using 3D bioprinting in regenerative medicine?

Here are some major forces behind the trend of adapting 3D bioprinting in regenerative medicine in no particular order:

1. Organ shortage is a long-term crisis

A quick glance at the HRSA.gov statistics, the numbers are staggering. While organ transplantation is a miracle treatment for many, the simple mismatch in supply and demand of available donors and transplantable organs severely limits the benefit of transplantation.  Regenerative medicine, including bioprinting

copyright: https://data.hrsa.gov/topics/health-systems/organ-donation

2. Tissue engineering is hard.

There are three “classical” approaches in tissue engineering [6]:

1. Cells, such as stem cell implantation; 

2. Bioactive molecules, such as growth factors, structural proteins, angiogenic

factors, cytokines, hormones, DNA, RNA, etc.

3. Combination of cells and biomaterials seeded into a porous three-dimensional scaffold;

All of these products can be injected or implanted into the human body to promote local tissue restoration. The key to the therapeutic effects of these is the end cellular response, which is the differentiation and growth of stem cells transplanted or existing host cells at the location of injection or implantation. Some of the major success factors include correct cell-cell interaction, cell-ECM (extracellular matrix) interaction and cell response to mechanical or environmental stimuli. Sometimes, anything outside of the stem cells is collectively called “microenvironments”. 

The philosophy behind tissue engineering is that if we can artificially recreate the native tissue in components, structures, and physical properties as closely as possible, then we can create an artificial tissue that is “close enough” in both structure and function. This is still just a hypothesis.

However, due to limited input control, classical tissue engineering can only create over-simplified tissue constructs, ending up with unrealistic engineered tissue and microenvironment, or far from “close enough”. That is, the classical methods do not enable us to reach that “biomimetic” goal. Instead, 3D bioprinting seems to enable us closer to that goal.  In the recent decade, an increasing number of researchers and companies started to use 3D bioprinting to enhance existing tissue engineering strategies.

Some of the major advantages of 3D bioprinting include: 

  • Increased control: Increased control is often listed as the number one reason for using 3D bioprinting. 3D printing can create more precise and customized scaffolds based on CAD design. Cell and biomaterial deposition precision is improved, allowing for improved control over the microenvironment, and enabling more biomimetic tissue products. The degree of control of the end product quality allows for improved repeatability, scalability, and quality control.
  • Expanded design capabilities. The ability to transform any CAD design into a 3D structure allows for an almost infinite number of new designs. The concept borrowed from the additive manufacturing industry, “complexity for free”, can be adapted in 3D bioprinting. The designers not only can design the scaffold geometry, but they can also design the spatiotemporal deposition workflow of bio-inks/cells in order to optimize neovascularization. 
  • Automation and the potential for large-scale tissue production. The automated part is not just limited to the 3D printing process itself, but also the entire workflow of the manufacturing process. We have published a number of related blogs on this subject. 
  • Solving the vascularization challenge. This is still a maybe, but 3D bioprinting is perhaps one of the best tools we have to achieve bigger, thicker, fully vascularized implantable tissues. In classical tissue engineering, in vitro tissue-engineered constructs are limited in size and thickness. Upon in vivo implantation, angiogenesis could take days, and perfusion will be unable to occur beyond a few hundred micrometers of the implanted tissue, significantly limiting application. 
  • Customizable bio-inks. A simple patent search reveals bio-ink to be one of the most active spaces of patent publication. Creative bioink design is often the key to solving existing tissue engineering challenges. For example, one challenge is poor growth factor delivery. However, this can be solved if one could growth factors into bioprinted scaffolds.

3. Changing regulatory environment:

First of all, several regulatory milestones are accelerating the research and commercialization of better alternatives to animal testing:

2013: EU bans cosmetic animal testing [14]

After two-decade-long efforts in the EU, in 2013, EU Directive 76/768/EEC (Cosmetics Directive) established “a testing ban i.e. it is prohibited to test a finished cosmetic product and its ingredients on animals in the EU; and a marketing ban i.e. it is prohibited to market a finished cosmetic product or its ingredients in the EU if they are tested on animals.”

“Between 2007 and 2011 the EU spent €238 million on funding non-animal replacement tests – a testament to its concern about animal welfare, the 3Rs, and the quest to find alternative methods.”

Needless to say, this explains why some of the earliest commercialized bioprinting products focus on the skin. We have a guide focusing on bioprinting skin for those who are interested.

2021: EMA implements new measures to minimize animal testing during drug development. [15]

In 2021, European Medicine Agency pushes forward continuous efforts against animal testing in the pharmaceutical industry. “The Agency promotes three principles — replace, reduce and refine; commonly referred to as 3Rs — through EMA’s Innovation Task Force (ITF). This action will facilitate the development and implementation of New Approach Methodologies (NAMs) that are in line with the European Union legislation on the protection of animals used for scientific purposes.” Alternative approaches to animal models mentioned included tests based on human and animal cells, organoids, organ-on-chips, and in silico modeling.

2021: Congress passes the FDA Modernization Act of 2021. [16]

Introduced in House (04/15/2021), this bill amends the Federal Food, Drug, and Cosmetic Act to allow manufacturers and sponsors of a drug to use alternative testing methods to animal testing to investigate the safety and effectiveness of a drug, and for other purposes. The regulatory landscape is clarifying.

Which organ systems or applications are making progress?

While many still think bioprinting organs or even tissues are at the sci-fi stage of development, solid scientific progress has been made to nearly all the organ systems in the human body, some more successful than others. The commercial interests in different organ systems mirror public health needs. However, any clinical and commercial success in any organ system will prove immediately ground-breaking and the beginning of a new era in medicine.

This is yet to be seen. 

This article is not another review article on technical and scientific advancements, and interested readers can check out the reference section for some recent publications. Our aim here is to focus on companies emerging as leaders in each of the eleven organ systems that we are trying to replicate. While a majority of companies have the recreation of a functional end organ as the company goal, many have also added or pivoted to other related applications including but not limited to: 

  • Disease modeling
  • Drug discovery
  • High-throughput screening

Many companies consider these three commercial categories more viable in the near term and are vital to financially support their larger longer-term regenerative medicine goals such as creating artificial organs. These three categories can also be arguably considered part of regenerative medical science. 

(3DHEALS blog has also published many bioprinting-focused Expert Corner blogs, interviews, and hosted events, aiming to provide our audience with a diverse perspective.)

Vijayavenkataraman, et al[7] reviewed advancements made in eleven organ systems that included skeletal, muscular, nervous, lymphatic, endocrine, reproductive, integumentary, respiratory, digestive, urinary, and circulatory systems. I would add 3D bioprinted cornea and eye components as a separate 12th organ system. 

Since 2018, the 3DHEALS Pitch3D program has discovered startups focusing on each of these major organ systems, indicating the market viability of such commercial activities. In fact, the latest 3DHEALS Company Directory includes 123 bioprinting-related companies, of which nine are microfluidics (or organ-on-a-chip), one bioreactor company, and many more produce special bioink. We will include some of the companies in this system-based discussion: 

1. Bone

Bioprinting bone or bone-like scaffolds is perhaps one of the most active fields of commercialization due to the exceptionally high demand for functional bone grafts [7]. Some of the notable companies include Osteopore (Singapore), Ossiform(Denmark, previously known as Particle 3D), DimensionInx(U.S., Chicago), and Cerhum(Belgium).

You can find our on-demand bioprinting bone event here.

We have quite a few Expert Corner blogs in the past related to this subject, so I will not repeat the technical aspect of bone bioprinting:

3D Bioprinting Bone – One Defect At A Time

3D Printing Bone: A Novel Way to Study Bone Diseases In Vitro

Bone Grafts: Inducing Bone Regeneration with 3D Printed Porosity


Osteopore offers 3D-printed biodegradable patient-specific implants using various polycaprolactone (PCL) based acellular scaffolds. The company claims their implants be degraded completely over 18 to 24 months with no foreign body residue through simple hydrolysis. The company claims its implant attains a structural stiffness similar to cancellous bone. 



Ossiform uses proprietary 3D printed ß-tricalcium phosphate implants to make customized patient-specific bone implant. The implant offers a resorbable implant with unique bone-like porosity. The company’s P3D Bone PSI demonstrates osteoconduction with a rapid formation of new vascularized bone, osseointegration with native bone, and simultaneous and balanced biosorption.


 Dimension Inx develops advanced 3D-printable biomaterials(“3D-Paints”), which include tissue repair and regenerative biologics, metals, alloys, ceramics, graphene/graphite/CNTs, and much more at room temperature using extrusion-based 3D printing technology. Some of its major products in development include patient-specific customizable acellular bone implants, one of which is called “hyperelastic bone”. 

Several hundred distinct 3D-paints have been developed to date. 


CERHUM is a Belgian startup that manufactures human bone grafts made of bioceramics. The company has developed a proprietary product called MyBone. MyBone is a custom-made bone graft made of hydroxyapatite with a controlled porosity that can be customized to a patient’s bone defect. It is the combination of the hydroxyapatite, the controlled porosity, and patient-specific geometry that makes MyBone a unique offering for bone repair.

2. Cartilage

Another area in regenerative medicine that has a large market is in treating degenerative joint disease. Osteoarthritis is a degenerative process characterized by progressive loss of hyaline cartilage in the synovial joints. This condition not just affect older adults (approximately 37% of adults over 65 years old [7]), but also many younger adults prematurely secondary to traumatic injury who are not yet candidates for conventional arthroplasty treatments. According to Nanochon, a startup in the space focusing entirely on cartilage, currently, there is no available medical device or standard of treatment on the market for the repair of advanced joint injury in adults ages 18 to 55. The younger adult market is potentially even larger than the > 65-year-old market. 

This presents an economic burden of $3.4 to $13.2 billion per year in the United States alone [7].

Many bioprinting startups have worked on cartilaginous tissue because it is a relatively avascular low-cell density tissue that is comparatively easier to be bioprinted than vascularized highly-complex tissues.[7] 

One of the most visible startups in this space is Nanochon, which aims to deliver off-the-shelf solutions that allow patients to return to activities via minimally invasive procedures.  Its product, Chondrograft™, replaces lost or damaged cartilage and encourages new growth using innovative materials and 3D-printed designs. Currently, its product is undergoing clinical trials for FDA approval. 

Similar to many other upcoming bioprinted transplantable tissue grafts, Chondrograft™ is an acellular 3-D cartilage implant (scaffold) made through the unique combination of synthetic micro/nanomaterial (e.g. PCL) and proprietary 3-D printing designs that mimic the porosity and structure of natural collagen fibers that exist in cartilage. Because of the highly controlled microenvironment, it has been shown in animal studies that the graft can generate new cartilage via correct stem cell differentiation and growth. 

You can read more about tissue engineering for bone and cartilage here:

An Introduction to Scaffolds for Tissue Engineering of the Bone and Cartilage

Bio Fabrication Techniques for Bone and Cartilage Tissue Regeneration

3. Muscle

There are types of muscles, namely skeletal, cardiac and smooth muscles. Cardiac and smooth muscle bioprinting will be discussed below in the cardiovascular system and digestive systems sections. In this section, we will focus on skeletal muscles attached to the bones and are responsible for voluntary skeletal movements. Conventionally treatment for severe skeletal muscle injury is autograft. Likely due to the challenges related to large size, complex tissue interface, vascularization, and innervation needs, there is not much research focusing on bioprinting muscle [7], and there is no startup to date focusing exclusively on commercializing skeletal muscle bioprinting products. Electrospinning, an adjacent biofabrication technique, has been shown to be potentially useful to manufacture muscle fiber. [7]

However, there are commercial interests in using bioprinting process to create smaller tissue models for pharmaceutical interests. For example, in 2021, a group of Novartis researchers published in Nature a Matrigel-based 3D bioprinted 3D human skeletal muscle model in microplates, which can be used in drug screening. More specifically, screening for drugs that could cause muscle wasting disease.  [9] The researchers described a 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. A functional muscle model exhibiting both structural and functional characteristics was successfully created, with the demonstration of appropriate responses to chemical stimuli such as caffeine. This is perhaps one of the more important pharmaceutical industry-backed bioprinting data. In particular, the structural and functional superiority of a 3D bioprinted model over conventional 2D cell culture was well demonstrated. In particular, core muscle functions such as contractile force and fatigue. [9] 

4. Nervous System

By serendipity, one of the earliest bioprinting applications 3DHEALS came across was brain tissue, mainly through the works of professor Stephanie Willerth. Professor Willerth also authors several 3DHEALS Expert Corner blogs focusing on bioprinting personalized brain and disease models for either tumor or neurodegenerative disease. Needless to say, with an aging population with many unsolved neurological diseases, the potential market for either biomimetic tissue or disease modeling is huge. For example, research and drug development for neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease) can benefit from having a better disease model. Brain tumor patients can also benefit from having a personalized tissue model for drug screening studies without having to go through toxic yet ineffective treatments. 

While the brain is very complex to replicate due to its layered structure, this actually makes additive manufacturing technology attractive given the advantages mentioned above. That said, successfully creating such bioprinted tissue or disease model relies not just on initial bioprinted structure, but also on an optimal concoction of chemical and mechanical signal, stem cell technology, and bioink technology. One company that is worthy of mentioning for this space is Axolotl Biosciences, a Canadian startup co-founded by professor Stephanie Willerth and her postdocs in 2020. 

Axolotl Biosciences focuses on its “novel bioink capable of printing hiPSC-derived neural cells that maintain high levels of cell viability for over a month”. One of its bioink, TissuePrint, is a fibrin-based bioink for extrusion-based bioprinters. It can support multiple different cell lines such as patient-derived human-induced pluripotent stem cells (hiPSCs), neural progenitor cells (NPCs), and mesenchymal stem cells (MSCs). Neurobioink allows for long-term culture, high cell viability, and promotes neuronal differentiation.

5. Lymphatic System

Engineering artificial lymph nodes and lymphatic vessels is a relatively new field, compared to the other engineered tissues. However, one later-stage startup Prellis Biologics is pushing both the scientific and commercial boundaries since the start of the COVID-19 pandemic. Before the pandemic, like many other bioprinting startups, Prellis was focusing on the vascularization of solid organs. 

However, since the start of the pandemic, Prellis Biologics pivoted to focus on applications surrounding 3D bioprinting lymph nodes for drug discovery and development. Prellis’ Externalized Immune System (EXIS™) platform recreates human immunobiology in vitro in the form of lymph node organoids (LNOs™). 3D printed LNOs™ allow direct access to a fully functional human immune system for antibody discovery, immunogenicity evaluation, and vaccine development.

Prellis’ proprietary, industry-leading two-photon 3D printing technology supports large, complex tumor co-culture systems mimicking tumor microenvironments, enabling the interrogation of interactive biological systems for uniquely relevant prioritization of immuno-oncology therapeutics. Its printer remains to have one of the fastest bioprinting technology with highest resolution in the industry, albeit at a hefty price. 

6. Integument

The integumentary system consists of skin, nails, hair, and the glands and nerves on the skin. The integumentary system acts as a physical barrier — protecting the body from bacteria, infection, injury, and sunlight. It also helps regulate body temperature and allows us to feel skin sensations like hot and cold. [9] However, among these, bioprinting skin commercialization is the most advanced and is currently under clinical trials. We have written extensively on 3D bioprinting skin as a part of 3DHEALS Guides.

There are two main applications for bioprinted skin products: 1) testing and 2) skin replacement as we have previously discussed. The global advanced wound care market is projected to reach USD 12.8 billion by 2026 from USD 9.4 billion in 2021, at a CAGR of 6.2% based on one market report. Concurrent with traditional bioprinting systems, there is also a growing trend in creating in situ skin bioprinting systems, which was described by professor Axel Guenther during our previous event.

There are several companies that are notable in the space: 

With an incredibly diverse and large portfolio of tissue engineering technologies, Cellink/BICO offers a variety of products including a variety of bioprinters (from extrusion to laser-assisted bioprinting), materials, and workflow specifically for in-vitro tissue models and analogous skin production.


Poietis is a Bordeaux, France-based startup that has been active in bioprinting skin space for about a decade, and it offers both hardware products, service, and 3D construct (Poieskin®).

Poieskin® is a bioprinted human full-thickness skin model that consists of a dermal layer of primary human fibroblasts embedded in a collagen I matrix overlaid by a stratified epidermis derived from primary human keratinocytes. It aims to start Phase I clinical trial with Poieskin® in 2022 according to CEO/founder Fabien Guillemot during our past webinar, which will be considered a milestone not just for bioprinted skin model, but perhaps for the whole industry. For those who are interested, we have also done an interview with Fabien recently.

Inventia Life Sciences 

Inventia Life Sciences is an Australia-based startup that focuses on DOD (drop-on-demand) bioprinting techniques to create tissue models and organoids for a variety of organ systems including the skin. Currently, the company offers bioprinter, materials, and workflow, aiming at drug discovery, screening, and biomedical research.

Mimix Bio


MimiX Biotherapeutics, a Swiss startup that developed sound-induced bioprinting is a new comer to the bioprinting skin product space. Its proprietary FastSkin tissue, an advanced dermal substitute for acute and chronic wound treatment, is a point of care product that uses a unique biofabrication technique called Sound Induced Morphogenesis (SIM).  “Controlled remotely by acoustic waves, SIM allows to pattern of biological material such as cells, organoids, or tissue fragments into three-dimensional constructs that develop into in vitro engineered tissues.” SIM represents a faster and more efficient way of multi-cellular assemblies at defined spatial resolution and cell density. The company aims to go through FDA clearance for FastSkin soon. This will also be one of first acoustic cell patterning clinical product in the world if it is successful. Another application for MimixBio’s technology was for biofabricating vasculatures, which we will discuss later.


CTIBiotech is a formidable force in the emerging biofabrication space. Located in Lyon, France, the company uses a variety of tissue engineering techniques including 3D bioprinting, bioreactors to develop or co-develop models and bioassays focusing on skin color, (skin) lymphatic systems,  skin appendages. More specifically, they are currently focusing on the following:

• Ex vivo baby skin models

• In vitro hair models

• Sebaceous gland models

• Pigmentation models

• Scar and stretch marks models

• Sensitive skin models

Other works in progress include an in-situ skin bioprinting system for acute wound care, which was described by professor Axel Guenther during our previous event. More interested readers can also refer to this 3DHEALS Guide.

While it is evident that skin bioprinting may be the first to reach commercialization success, there are still plenty of challenges ahead to reconstructing in vitro a fully-functional skin with all the cell types and skin appendages. [7]

7. Endocrine system

The current treatment method for hormonal or gland dysfunction is hormone replacement therapy. For example, diabetic patients receive insulin, and hypothyroid patients receive thyroxin. However, this is far from ideal, especially for diabetics, because of the lack of perfect coordination to mimic all the physiological conditions in a patient’s daily life. [7] Of all the endocrine organs, the pancreas has been the major commercial focus, but creating an ex-situ functional pancreas is extremely difficult due to its complexity. For example, the islets of Langerhans, which are responsible for hormone production, have at least five types of cells namely alpha cells (secreting glucagon), beta cells (secreting insulin and amylin), delta cells (secreting somatostatin), gamma cells (secreting pancreatic polypeptide), and epsilon cells (secreting ghrelin) in varying percentages, arranged in a particular cytoarchitecture. However, bioprinting is probably the only existing technology that allows for precise recreation of this complexity. There has been a minor success in creating a printed construct that can mimic insulin response to glucose stimuli for up to 12 weeks in mice, but the field faces both technical and commercial challenges. Technical challenges include a lack of available primary cells from endocrinal glands, a lack of proper bioinks that can maintain cell viability, glucose permeability, and sensitivity of endocrinal cells to the environment, among others. Commercial challenges include existing diabetic treatment strategies such as effective insulin management with an insulin pump and continuous glucose monitor (CGM), which is collectively called the “Artificial Pancreas System” by the FDA.  

There are three companies that are worth mentioning in the space of biofabrication of pancreas: 


Founded in 2009 and privately held, InSphero is headquartered in Schlieren, Switzerland with subsidiaries in the United States (Brunswick, ME) and Waldshut, Germany.  

While the company does not use 3D bioprinting to create its 3D cell culture, InSphero has commercialized in vitro 3D islet cell microtissues, called 3D InSight™ Islet Microtissues for pharmaceutical research and drug discovery. This end goal is shared by many 3D bioprinting startups. The company a proprietary process for production of standardized islet models. The process starts with gentle dissociation of primary human islets followed by scaffold-free re-aggregation to produce the 3D InSight™ Islet Microtissues, which are homogeneous in size and cellular composition, free of exocrine contaminants, and in a high-throughput-compatible cell culture format that supports long-term experiments in vitro.  In addition to islet cell model, the company also produces liver and tumor 3D cell culture models. 


Readily3D is a Switzerland-based 3D bioprinting startup, using a tomographic (or volumetric) 3D printing technique, where shaped light from different angles rapidly solidifies photosensitive inks in three dimensions. As the entire build volume is illuminated simultaneously, centimeter-scale microtissue are produced in just a few seconds. After bioprinting, the object is simply separated from the uncured ink and collected. “The remarkably low photoinitiator content (eg 1mg/mL LAP) and low light dose (<600 mJ/cm²) make tomographic bioprinting a cell-friendly technique.” 

The company has taken the first step towards developing a 3D bioprinted living model of the human pancreas for testing diabetes medicines. Readily3D’s novel technology is reportedly capable of accomplishing such goals at scale and efficiently. 


Polbionica is a spin off from the Foundation of Research and Science Development in Poland, bringing to market the research developed in the BIONIC project. The company’s mission is to introduce 3D bioprinting of the bionic pancreas to clinical practice.

On the 14th of March 2019, its research team claimed success in creating a prototype of a “bionic pancreas suitable for transplantation, based on printed 3D scaffolds, functional vessels and pancreatic islets.”   This prototype bionic pancreas had a dimension of 3x3x5 cm. The next stages of research include connecting the bionic pancreas to a bioreactor (to stay viable and grow), directly print stem cells that can then be converted to functional alpha or beta cells, and animal testing. 

Aspect Biosystems

Aspect Biosystems is one of the earliest bioprinting startups using microfluidics devices as a critical component in their technology. Currently, the company focuses on developing or co-developing pancreatic and liver tissue for cell therapy.

In 2023, Aspect Biosystems signed major agreements to partner with Novo Nordisk to co-develop cell therapy for diabetics.

8. Circulatory System – heart components, vessels, vascular networks

The cardiovascular system consists of the heart, arteries, veins, and capillaries. The unmet needs in this space are obvious, given heart disease remains the number one killer in the United States based on the latest CDC data. For those who are interested in learning directly from experts, we have hosted a webinar in the past focusing on bioprinting vasculatures and cardiovascular systems. Stay tuned for dedicated 3DHEALS Guides for more in-depth evaluation. 

More than 80,000 heart-valve replacements are performed annually in the US alone.[7] While existing mechanical and biological prosthetic valves have saved millions of lives, neither is completely ideal. For example, while mechanical valves have high durability, recipients must take blood-thinning medications for the rest of their lives due to the thrombogenicity of such valves. Biological prosthetic valves (xenografts or allografts) can lead to immune rejection, quicker degeneration, and thrombosis, often requiring repeat surgery. While traditional tissue engineering has failed to replicate the native valve geometries and properly position heterogeneous cell populations, bioprinting appears to be an ideal candidate. One startup immediately comes to mind is Boston-based Fluidform3D, which focuses on using FRESH technique to produce a variety of heart components and models.

In addition to heart valves, researchers and startups are also working on printing myocardium as a cardiac patch, and heart models (“mini heart”) for drug development/discovery. There was evidence demonstrating bioprinted tissues with precise spatial cell arrangement are superior to the control sample in terms of vascularization, capillary density, and functionality in the infarcted hearts in animal-recipients.[7]  The research community continues to optimize the technology in terms of cell viability, gene expression, scalability, and functionality. We have invited several speakers to speak on these near-commercialization techniques in creating “mini hearts” or “cardiac patches” recently.

Here are some of the worth-mentioning startups in the space:


Fluidform’s patented FRESH™ technology (off CMU) has been shown to be able to produce real functional beating human ventricles and heart valves, recreate complex branching vasculature down to the capillary scale, tailor alignment of cells to create muscle fibers and tissue anisotropy, and promote tissue regeneration in large animal studies, and even scale up to full-size organs based. Currently it is focusing on two commercial goals:

1) Cardiotoxicity model for drug screening/discovery. The company is working on developing an in-vitro human heart model that detects complex arrhythmias early in the pre-clinical discovery process. The hypothesis is that existing in-vitro models for testing cardiotoxicity is inferior due to their lack of geometric complexity and size. 

2) Trans-catheter Aortic Valve. The team is working on a trans-catheter valve with reduced propensity for calcification, which is a common complication for existing valves. 


Matricelf developed a technology that enables the production of autologous engineered tissue composed of matrix and cells derived from patients omentum biopsy. The omentum-based hydrogel can be used to create autologous implants, either as bioink for 3D printing of tissues and organs or other tissue engineering methods. The printed tissues and organs can potentially match the immunological, biochemical, and anatomical properties of the patient. The company recently licensed the technology that enabled scientist at Tel Aviv university that 3D printed a human heart from human cells and matrix for the first time in human history. The company plans to conduct its first human clinical trial for Acute Spinal Cord Injury (SCI) in 2024.

Mimix Bio
Mimix Bio


We have introduced MimixBio in our previous section focusing on skin bioprinting, which seems to be their first large scale commercialization goal. However, using the same acoustic bioprinting and cell patterning technique, MimixBio has also made progress in creating vasculatures, especially microvasculatures. Its recent research showed that local cell density and close proximity of endothelial cells is crucial for the formation of perfusable vascular structures. Specifically, it was shown that endothelial cells can be assembled by low frequency sound, leading to increased branching at lower initial cell seeding density compared to a standard microfluidic approach. Its research is driven by the hypothesis that local cell density enhancement of endothelial cells recreates the physiological cell density and thus favours in vitro vasculogenesis. The company is currently exploiting the different possibilities within the mimix labware and biomaterial portfolio to generate vascular structures. It aims to be able to eventually commercialize a robust and highly reproducible system for in vitro evaluation of angiogenic/antiangiogenic drugs and will be implemented in tissue engineering approaches.

9. Respiratory System

The respiratory system consists of lungs, pharynx, larynx, trachea, bronchi, and diaphragm and is responsible for the exchange of oxygen and carbon dioxide between the atmosphere and the body. Compared to advancements in other organ systems, treatment strategies for lung diseases appear relatively stagnant. Human lungs lack regeneration ability and lung transplantation is the only way to treat severe lung diseases [7]. Therefore, better biomimetic lung tissues would help with developing new drugs, understanding diseases, and ultimately providing tissue transplants. 

 The space of lung bioprinting was quiet until June 2022, when United Therapeutics (Lung Biotechnology PBC) and 3D Systems revealed the latest development regarding their bioprinting platform, having successfully 3D printed a human lung scaffold capable of demonstrating gas exchange in animal models.

The 3D printable lung scaffold design consists of what the company claims is a record 44 trillion voxels that layout 4,000 km of pulmonary capillaries and 200 million alveoli. Going forwards, United Therapeutics and 3D Systems are planning to cellularized their 3D printed scaffolds with a patient’s own stem cells to fabricate transplantable full human lungs which will not require immunosuppression to prevent rejection.

The recent acquisition of VolumetricBio by 3D Systems, a Texas-based startup, will certainly add scalable production technologies and talents to this partnership. 

10. Digestive System – Liver

There are two main components that make up the digestive system: 1) the Alimentary tract that includes the mouth, esophagus, stomach, small and large intestines, rectum, and anus 2) Solid organs that include the liver, pancreas (also part of the endocrine system), and biliary system (including the gallbladder). Of these the liver, pancreas (see previous section), bowel, and esophagus are the main research interests in regenerative medicine. There were also multiple attempts to commercialize bioprinted liver products for decades, most notably from the earlier works by Organovo

While the liver has a certain amount of regenerative ability, many with liver cancer, cirrhosis, and liver failure due to other causes will require transplantation to survive. The demand for liver transplants globally is estimated to increase by 23% in the next 20 years. [7] That said, a living donor transplant is an option for some liver transplant candidates, which could be competing technology to ex vivo biofabrication.

That said, publications on tissue engineering of the liver can be found as early as 1996. Despite its structural complexity of having interwoven biliary, lymphatic, and vascular networks, bioprinting functional liver tissues using either primary hepatocytes (which is again scarce) or stem cells have shown significant progress in the last decade. These printed liver tissues are not only shown to metabolize chemicals as expected but also secrete bile. Achieving functional implantable liver tissue appears closer than ever. However, some of the major challenges, similar to other organ systems, include a lack of available primary hepatocytes and  [7] 

11. Urological – Kidney

The urinary system includes the kidney, bladder, urethra, and collecting system. Of these, implantable kidneys and bladder are the most needed. The main functions of this system include the excretion of bodily wastes, regulation of blood pH, electrolytes, and metabolites, as well as performing endocrinological, metabolic, immunologic, and hemodynamic functions.

There has been immense interest in tissue engineering kidneys. Currently, there are nearly half a million end-stage renal disease patients who rely on dialysis in the U.S. Many are also on the waiting list for kidney transplants. However, neither dialysis nor transplantation is a satisfactory solution. [7] 

Research in tissue engineering kidneys has been ongoing since the 1980s, however, it is only recently there is commercialization of biofabrication of implantable kidney tissues by Trestle Biotherapeutics, a startup spin off the Wyss institute. While the exact process used by Trestle is not yet disclosed to the public, it is presumed that it will rely on biofabrication technologies, including 3D bioprinting technologies developed by Dr. Jennifer Lewis and  the company has revealed that it “paves the way to increasing tissue maturation and vascular development within stem cell-derived organoids in response to fluid flow.” Given that it achieves high viability and vascularization, two traditional hurdles to 3D bioprinting functional tissues, Trestle Biotherapeutics says the process could soon yield implants that “supplement, or even replace, renal function in patients.” 

One question you may ask is, “what about 3D printed bladder? While tissue-engineered bladders have been successfully implanted into patients by Dr. Anthony Atala, a pioneer in regenerative medicine and urologist, there has been no truly 3D bioprinted bladder. However, more than 400K patients worldwide experience bladder dysfunction, and there certainly is a significant market for it.

12. Reproductive system

Decreasing birth rate will negatively impact both one’s community and its economy. While decreasing birth rate can be due to a combination of social and biological issues, the problem that biomedical engineering and regenerative medicine can solve is tackling biological causes of infertility. Estimates suggest that between 48 million couples and 186 million individuals live with infertility globally. [WHO] Another emerging field for pediatric cancer patients receiving aggressive treatments, oncofertility, is an increasing driving force to invest in fertility preservation.

Most of the tissue engineering studies pertaining to infertility focused on the female reproductive system, however, there have been attempts to tissue engineer artificial testis. [7] 

While not many researchers or companies are bioprinting reproductive tissue, Dimension Inx, a biomaterial/bioprinting startup out of Northwestern University in Chicago is one of the first companies focusing on this area. In Nov 2022, the company and Lurie Children’s Hospital of Chicago were awarded a joint NIH grant to expand fertility restoration options

“In prior work developing bioprosthetic ovaries, the team was able to boost hormone production and restored fertility in mice using 3D-printed gelatin scaffolds. After removing a female mouse’s ovary and replacing it with isolated ovarian follicles seeded in the 3D-printed scaffold, this bioprosthetic ovary enabled the mouse to ovulate and give birth to healthy pups.” [10] 

13. Eyes

Blindness is perhaps one of the most devastating disabilities. Fortunately, because of the layer organization of components of the eye, biofabrication and bioprinting seem to be promising tools that allow potential tissue regeneration of these critical components. The latest commercial interests in the ophthalmology space lie in solving challenges with traditional cornea transplants and the regeneration of retinas in combating AMD (age-related macular degeneration). 

It is estimated that around 13 million patients are in need of corneal transplantation but only 1 in 70 of

the affected population receives a healthy donor tissue for transplant, plus the wait time for a corneal transplant can vary between 1 and 24 months [10]. 

The goals of biofabrication include not just hierarchical assembly of the 3D biological structures, but also a recapitulation of optical and mechanical performance comparable to native tissue. There are two startups in the space that is worth mentioning: 


Pandorum technologies

Pandorum technologies is an Indian startup that has been working on tissue engineered human cornea since 2010. While the company also has focus on liver and lungs, it is best known for being the first mover in the space of cornea repair using tissue engineering and 3D bioprinting. It has two main products, which include a proprietary hydrogel formation that can be used to repair cornea damage directly, called “liquid cornea”  and a bioengineered cornea lenticule using additive manufacturing.

Liquid cornea is a regenerative treatment that can accelerate the growth of host tissue. “The trigger for this growth is provided by a bioactive component, the exosomes delivered to the wound site, embedded in the biopolymeric matrix. These exosomes are derived from the population of predominant cell types in the cornea. They are programmed to promote scarless wound healing, to restore vision, the primary function of the cornea and eye.” Currently, this is undergoing pre-clinical animal trials and is likely an earlier commercialize product from the company. 

Precise Bio

Founded in 2015, Precise Bio is a North Carolina / Israel regenerative medicine startup focusing on bioprinted ophthalmologic products, including cornea-related products. Similar to Pandorum, Precise Bio also aims to solve the cornea transplant shortage by biofabricating/bioprinting transplantable cornea, which is in the preclinical phase. However, the company also offers additional tissue engineering products for the eye:

  • Retinal patch: Targeted treatment for Age-related macular degeneration (AMD)
  • Vision correction lenticules (implant): Offering a new approach to solving refractive errors
  • Ocular surface disorders: Targeting various conditions involving damaged cornea surface or Limbal Stem Cell Deficiency

In addition to its ophthalmic pipeline, Precise Bio is also developing a 3D cardiac tissue “patch” for post-myocardial infarction (MI) implants in order to retrieve cardiac muscle viability and functionality.  


  1. A history of EU ban on cosmetic animal testing
  2. EMA implements new measures to minimise animal testing during medicines development
  3. FDA Modernization Act of 2021
  4. Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine 
  5. Regenerative medicine – Wikipedia
  6. Applications of 3D Bioprinting in Tissue Engineering and Regenerative Medicine
  7. 3D bioprinting of tissues and organs for regenerative medicine
  8. Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses
  9. Integumentary System (Cleveland Clinic)
  10. Dimension Inx and Lurie Children’s Hospital of Chicago awarded joint NIH grant to expand fertility restoration options
  11. Print me a cornea – Are we there yet?

3D Printing In Hospitals: A Beginner’s Guide 1/5

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