The number of patients with organ failure has increased significantly, consequently driving up the demand for organ transplants worldwide. In the United States alone, around 47,000 organ transplant surgeries were performed in the previous year, representing a major increase of around 8 percent from 2022.1
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The majority of live donor transplants are kidney transplant operations. Organ transplantation serves as a crucial life-saving intervention for individuals suffering from end-stage organ failure. Nonetheless, the scarcity of available organs results in extended waiting periods for patients, contributing to an increase in mortality rates.2
Recent advancements in tissue engineering and regenerative medicine have played a key role in biomedicine, with 3D bioprinting emerging as a pivotal technology in ongoing research and development efforts to address the organ shortage for transplants. Among the various techniques, laser-based 3D bioprinting is leading the way with numerous applications in bioengineering and research studies.
What is Bioprinting Technology?
In 3D printing technology for tissue or organ fabrication, drafting is performed by computer-aided software using a specific program that provides instructions to a machine for generating 3D scaffolds.3
3D bioprinting offers 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).4
The bioprinter operates 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.4
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.5 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.6 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.6 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.7
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.7 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.8
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.9
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.10 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.11
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.12
This challenge becomes particularly crucial as high resolution often entails prolonged fabrication times, which could potentially compromise cell viability over extended periods.
Finding ways to balance resolution with fabrication speed to ensure both fine detail and practical scalability will be essential for advancing bioprinting technology.
More from AZoOptics: Applications of Lasers in Additive Manufacturing
References and Further Reading
[1] Organ Procurement & Transplantation Network. (2024). Continued increase in organ donation drives new records in 2023; New milestones exceeded. [Online] Organ Procurement & Transplantation Network. Available at: https://optn.transplant.hrsa.gov/news/continued-increase-in-organ-donation-drives-new-records-in-2023-new-milestones-exceeded/ [Accessed on 15 March 2024].
[2] Samin, Y., et al. (2023). Barriers and Enablers to Joining the National Organ Donation Registry Among Patient Population at a Tertiary Care Hospital of Peshawar, Pakistan. Cureus. doi.org/10.7759/cureus.37997
[3] Sniderman, B., et al. (2016). 3D opportunity for life Additive manufacturing takes humanitarian action. [Online] Deloitte Review. Available at: https://www2.deloitte.com/content/dam/insights/us/articles/3d-printing-for-humanitarian-action/DR19_3DOpportunityForLife.pdf [Accessed on 16 March 2024].
[4] Miri, A., et al. (2019). Effective bioprinting resolution in tissue model fabrication. Lab on a Chip. doi.org/10.1039/C8LC01037D
[5] Agarwal, T., et al. (2021). Recent advances in bioprinting technologies for engineering cardiac tissue. Materials Science and Engineering. doi.org/10.1016/j.msec.2021.112057
[6] Hospodiuk, M. et al. (2017). The bioink: A comprehensive review on bioprintable materials. Biotechnology advances. doi.org/10.1016/j.biotechadv.2016.12.006
[7] Chang, J., et al. (2023). Laser-induced forward transfer based laser bioprinting in biomedical applications. Frontiers in Bioengineering and Biotechnology. doi.org/10.3389/fbioe.2023.1255782
[8] Koch, L., et al. (2021). Capillary-like Formations of Endothelial Cells in Defined Patterns Generated by Laser Bioprinting. Micromachines. doi.org/10.3390/mi12121538
[9] Huang, Q., et al. (2024). A three-dimensional (3D) liver–kidney on a chip with a biomimicking circulating system for drug safety evaluation. Lab on a Chip. doi.org/10.1039/D3LC00796K
[10] Vital 3D Technologies. (2024). Shaping The Future Of Medicine At The Speed Of Light. [Online] Vital 3D Technologies. Available at: https://www.vital3d.eu/
[11] Shen, Y., et al. (2020). DLP printing photocurable chitosan to build bio-constructs for tissue engineering. Carbohydrate polymers. doi.org/10.1016/j.carbpol.2020.115970
[12] Zandrini, T., et al. (2023). Breaking the resolution limits of 3D bioprinting: future opportunities and present challenges. Trends in Biotechnology. doi.org/10.1016/j.tibtech.2022.10.009
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