What is Bioprinting Technology?

3D bioprinting technology for tissue or organ fabrication involves drafting by computer-aided software using a specific program that instructs a machine to generate 3D scaffolds. 3D bioprinting provides precise control over construct fabrication and cell distribution, achieving printing resolutions close to the finest features of tissue microarchitecture, ranging from ten to a few hundred micrometers (μm). The bioprinter functions through a series of consecutive manufacturing operations guided by integrated computer numerical control machinery. The platform’s movement is directed by coordinates stored in file format throughout the printing process. Print conditions, including printing nozzle aperture, speed, and layer thickness, can vary significantly, each affecting cell survival and construct fidelity. Optimizing printability is essential to enhance the fabrication process and construct properties. Laser-assisted bioprinting, the most widely used technique in 3D bioprinting, relies on precise optical guidance, where a high-intensity laser propels bio-ink droplets in a non-contact mode. This method utilizes a pulsing laser beam and two parallel slides, a donor and a collector, to create the desired construct. A laser-absorbing metal layer beneath the donor slide is coated with the biomaterial to be transferred. The laser pulses have energies around 65 to 190 nJ. The metal layer absorbs these high-energy pulses, causing the biomaterial to melt and disperse from the donor slide onto the collector portion by passing through the evaporated metal. The laser transfers the bioink in laser-based 3D bioprinting. The role of bioink in laser-based 3D bioprinting is significant, and the accurate choice of bioink is necessary for the success of the process. Bioink can be defined as an amalgam of different types of biomaterials present in the form of a hydrogel, used during laser-based 3D bioprinting for transferring biomaterials.

The Advantages of Laser-Based BioPrinting

In modern biomedicine research and applications, Laser-Assisted Bioprinting (LAB) is a revolutionary technology extensively utilized in tissue engineering, organ printing, and regenerative medicine domains. It plays a pivotal role in biomedical innovations in transplantation, favored for its exceptionally low risk of contamination. During laser-based 3D bioprinting, cells experience far less mechanical stress, resulting in significantly higher cell viability.

Laser-based bioprinting for generating 3D-printed organs applies to a diverse range of biomaterials requiring excessive alterations. Compared to other methods like droplet-based bioprinting, laser-assisted 3D bioprinting boasts higher printing speeds, leading to superior resolution and accuracy. In terms of cell deposition, LAB enables precise control over the number of cells per droplet and facilitates high cell densities.

How is Laser-Based 3D Bioprinting Used to Print Organs?

3D bioprinting has significantly alleviated the shortage of organs for transplantation surgeries. Among laser-based methods, Laser-Induced Forward Transfer (LIFT) has gained popularity among biomedical experts. This technique utilizes a laser to transfer bioink onto a substrate, enabling the creation of intricate 3D structures with high precision, improved cell viability, and strong technical adaptability. Industrial experts and researchers have successfully utilized LIFT-based 3D bioprinting to print bones, cardiac muscles, neural tissues, and kidney glands, saving millions of lives annually. In the biomedical and tissue engineering research domain, there is a focus on resolving skin diseases by developing methods for human skin alternatives. The skin construct developed using laser-based 3D bioprinting typically involves sequentially depositing 20 layers of fibroblasts followed by 20 layers of keratinocytes onto Matriderm™ sheets. The skin substitutes generated with this technique have resolved extensive skin damage issues.

Several high-resolution bioprinting methods are available today, with laser-based bioprinting becoming the predominant alternative for developing multi-layered tissues with built-in capillaries, similar to the human body vascular system. Endothelial cells (ECs) are placed accurately on Matrigel substrates to form the inner lining of the blood vessels. Researchers have demonstrated the ability to arrange ECs in lines and grid patterns using laser-based bioprinting. At a high concentration of 100 million per mL, laser-based bioprinting of endothelial cells leads to the spontaneous organization of tubular structures resembling blood vessels, complete with lumens, within the Matrigel substrate. Detoxification and drug metabolism in the human body are crucial functions overseen by the liver and the kidneys. However, conventional methods for transplanting these organs, involving animal models and cell cultures, face significant limitations, including ethical dilemmas and genetic disparities. To address these challenges, researchers have developed a 3D liver-kidney on a chip with a biomimetic circulating system (LKOCBCS) using laser-based bioprinting for drug safety assessments.

The LKOCBCS comprises 3D biomimetic liver tissue resembling human liver lobules, created through 3D bioprinting and renal proximal tubule barriers fabricated using ultrafast laser-assisted etching. This innovative platform facilitates effective communication between the liver and kidney, facilitating the exchange of nutrients, compounds, and metabolites. Results from studies conducted using the LKOCBCS have demonstrated stable glucose concentrations and cell metabolism after seven days, indicating its potential utility for drug safety evaluations. Companies like Vital 3D Technologies are reshaping the future of medicine by enabling highly efficient and fast 3D bioprinting of organs. These companies leverage advanced 3D bioprinting technology to fabricate living tissues and organs with remarkable precision and control. They utilize advanced techniques to fabricate biocompatible scaffolds with ultra precision and consistency, ensuring their safety for application in living tissues. These frameworks play a central role in tissue engineering applications aimed at fabricating transplant tissues and organs and enhancing skin and other skin healing after injuries occur.

The Future of Laser-Based 3D Bioprinting

Light-based techniques such as SLA (stereolithography) and DLP (digital light processing) are becoming increasingly popular in bioprinting. However, their resolution typically remains within the range of several tens of micrometers. This limitation partly arises from the photochemistry of the crosslinking process, which often restricts lateral resolution rather than being constrained by the minimum laser spot or pixel size. Layer thickness is also inherently linked to the depth of light penetration. For example, researchers utilizing a micrometer-resolution DLP system discovered that, despite the theoretical optical capabilities of their setup, satisfactory features were achieved only within a lateral dimension of 100 μm and a vertical dimension of 300 μm. While the advantages of achieving precise, cell-instructive microscale and nanoscale features with laser-assisted 3D bioprinting are evident, there are looming challenges for future research. One such challenge is maintaining resolution while enabling the fabrication of clinically relevant size objects, typically in the centimeter-scale range. This challenge becomes particularly crucial as high resolution often entails prolonged fabrication times, which could potentially compromise cell viability over extended periods.