3D Bioprinting: The future of customized tissues and organ replacement

Posted: November 01, 2024

 Imagine you are at the hospital with liver failure. You need a new liver as soon as possible. Your surgeon takes a tiny tissue sample, some of your stem cells or perhaps just your DNA data and posts it to a 3D bioprinting company. A few days later, the organ tissue you need arrives in a sterile container via FedEx, ready for implantation. It sounds like science fiction, and it is, for now. But scientists are getting closer to printing living tissues, such as blood vessels, bones and skin.

What is 3D bioprinting?

3D printing emerged in the early 1980s. An American engineer, Charles Hull, built the first printer that could create solid objects by depositing successive layers of an acrylic-based photopolymer following a computer-aided design. This technology revolutionized the additive manufacturing industry. Unlike traditional manufacturing, which cuts away material to create objects, 3D printing builds up structures layer by layer.

Later researchers discovered that inkjet printers could spray out living cells without damaging them. The technique developed by R.J. Klebe used a modified inkjet printer to deposit cells in predetermined patterns. But it wasn’t until the 2000s that the medical field began using 3D printing.

3D bioprinting combines the principles of 3D printing with biology. Using a special material called bioink, made up of living cells, biomaterials, and bioactive molecules, researchers can create complex tissues and even organs similar to printing a photo.

A broad definition of 3D bioprinting includes the manufacture of structures that do not require biocompatibility, such as models for surgical planning; non-degradable products that must be biocompatible, like titanium alloy joints and silicone prostheses used for defect repairs; and biocompatible and degradable products, including biodegradable vascular stents and active ceramic bones, which are ceramic materials that can engage in biological processes that promote bone healing and regeneration. Such kinds of products have been used in the clinic for the past two decades.

True bioprinting in action—where living cells are arranged to form lifelike tissues—is more complex, but it opens up incredible medical possibilities, such as creating customized tissues for patients, testing new drugs more accurately, and advancing regenerative medicine. With methods like laser-assisted printing and micro-extrusion, scientists can carefully control how each layer is deposited, ensuring that the final product closely resembles natural tissues.

According to Grand View Research, the global 3D bioprinting market generated a revenue of over USD 2 billion in 2023 and is expected to reach USD 5 billion by 2030.

Getting the balance just right

Engineering effective bioinks requires a deep understanding of material science, biology, and fluid dynamics.

Bioinks for 3D bioprinting are made up of two main components: a hydrogel medium and suspended cells. The hydrogel, which is generally made from a blend of natural and synthetic polymers such as alginate and gelatin, must have precise physicochemical properties—such as viscosity and elasticity—to be extruded through a printing nozzle while retaining structural integrity after printing.   

The appropriate balance between the hydrogel ingredients and the density of different cell types is critical: too few cells can impede tissue growth, while too many can obstruct flow through the printing needle.   

Engineers face several challenges in this process, including optimizing rheological qualities for shear-thinning behavior, carefully managing cross-linking mechanisms to stabilize printed structures, and assuring high cell viability both before and after printing.  

Additionally, bioinks need to be customized for each tissue type in order to match its unique mechanical qualities and biochemical signals.

Which organs have already been bioprinted?

​​​Cornea: Researchers from Newcastle University in the UK created corneal structures that closely resemble the native human corneal stroma. They used an in-house collagen-based bioink containing encapsulated corneal keratocytes, cells in the cornea that provide structural support and transparency, which could live up to seven days. Another group at Florida A&M University also developed a new method for quickly bioprinting synthetic corneal structures for drug testing and research. These models hold their curvature and transparency, while the keratocytes survived for two weeks. Meanwhile, a group at Marmara University in Turkey printed a synthetic corneal-like tissue that can maintain normal intraocular pressure and perform essential cornea functions.

Skin: Researchers have created multilayered, multicellular skin models. At the Rensselaer Polytechnic Institute in Troy, New York, scientists implanted one such skin model in mice, demonstrating its ability to develop microvessels and achieve blood flow within four weeks. At the University of California, Los Angeles, another group uses these skin-like tissues for drug testing and research on skin diseases.

Bone: Researchers at the Hefei Institutes of Physical Science, Chinese Academy of Sciences have developed new 3D bioprinted materials combining bioactive boron-based glass (BBG) with polycaprolactone or sodium alginate to improve the repair of bone and soft tissues. They discovered that a composite containing 20% BBG was particularly effective for bone healing, while their new bioink improved printing accuracy and reduced shrinkage, promoting better cell attachment and healing.

Reproductive organs: In one study, researchers created 3D scaffolding to culture artificial ovaries, which, when implanted in a mouse, resulted in the birth of live offspring. Researchers from Huazhong University developed an ovarian scaffold using mouse cells that effectively supported the growth and development of mouse ovarian follicles.

Cardiac tissue: Researchers at the Biomanufacturing Center at Tsinghua University in Beijing have developed a new bioprinting method called SPIRIT, which uses a specialized microgel-based bioink that supports both the printing process and the formation of tissues. This approach allows the creation of complex structures, such as cardiac tissues and heart ventricle models with functioning blood vessels. The SPIRIT technique improves the speed and precision of printing intricate organ shapes and internal layouts.

Cancerous tissue: 3D bioprinting is revolutionizing cancer research by creating more accurate models of tumors and their environments. Traditional 2D cell cultures often fail to replicate the complex interactions in real tumors, making it challenging to study cancer behavior and test treatments effectively. In contrast, 3D bioprinting allows researchers to construct intricate, multicellular structures that closely mimic the tumor microenvironment.

Cruelty-free medicine

3D bioprinting presents a compelling alternative to traditional in vivo testing, reducing reliance on animal models and costs and improving accuracy of preclinical studies.

The drug development process is notoriously lengthy and expensive, with many drug candidates failing during clinical trials due to unforeseen toxicity and inefficiencies. Currently, the pharmaceutical industry uses animal testing to determine the viability of a new treatment. This step, which is currently essential, involves subjecting animals to various experimental treatments to determine safety, dose, and potential side effects. In addition to a significant cost, researchers must adhere to tight ethical guidelines, and the lab animals are sacrificed in the process.

3D bioprinting enables the creation of complex tissue models that more accurately replicate human physiological conditions, which can lead to more reliable data on drug efficacy and safety. This technology allows for high-throughput screening of compounds in a fraction of the time and cost associated with animal testing.

This shift not only has the potential to speed medical discoveries, but it also addresses ethical concerns, benefiting both humans and animals.