Tissue damage and degeneration are typical in humans; nevertheless, the human body's regenerative capacities are insufficient to deal with this stress. Traditional treatments for these diseases rely on tissue or organ transplantation. Transplantation depends on a donor's availability, which can be difficult to come by and comes with the risk of graft rejection owing to an immunological reaction. Tissue engineering and regenerative medicine are two topics that are quickly developing to address these problems.
Every year, more than 2.2 million people worldwide undergo bone graft surgery to fix flaws in their bones. Swansea University researchers have devised a bioprinting technology that can produce an artificial bone matrix in the exact shape of the bone needed, using a biocompatible, durable, and regenerative material. These newly printed 'bones' are implanted into the body, where they fuse with and are subsequently replaced by a patient's native bones over the course of many months with few if any, issues. It takes about two hours to print a tiny bone with trabecular properties right now. With such fast turnaround times, surgeons may soon be printing them while they operate in the operating room.
The same goes for the skin! If a person is severely burned, healthy skin from another body region might be extracted and applied to the damaged area. However, there are situations when there isn't enough undamaged skin to harvest. Wake Forest School of Medicine researchers have successfully designed, manufactured, and tested a printer capable of printing skin cells directly into a burn lesion.
Because the skin is a multilayered organ with diverse cell kinds, 3D printers print in layers, perfectly suited to this type of technology.
What is 3D Bioprinting?
3D Bioprinting is the process of printing biomedical structures from living cells, biological substances, and biomaterials in three dimensions. In simple terms, 3D Bioprinting is the layer-by-layer deposition of biological material to build 3D structures such as tissues and organs.
Bioprinting is a kind of additive manufacturing that involves the creation of materials for use in industrial settings. 3D bioprinting starts with a proper microarchitecture, which is then stabilized by cell and tissue scaffolds, all while considering the influence of production on cell viability.
Three distinct ways to 3D Bioprinting are used
1. Biomimicry
Biomimicry is the process of creating exact replicas of cellular and extracellular components of tissues and organs after studying nature closely.
2. Autonomous Self-assembly
The method of duplicating biological tissue utilizing the mechanism of embryonic tissue and organ development as a guide is known as autonomous self-assembly.
3. Mini Tissue Building Blocks
The method of both of the previous strategies is combined in the mini tissue building blocks approach. Small functional components of tissues and organs, known as mini-tissues, are created using this bioprinting method.
Basics of 3D Bioprinting (Process)
Pre-bioprinting, Bioprinting, and post-bioprinting are the three processes that make up the total process of 3D Bioprinting.
Pre-Bioprinting
Prebioprinting begins with the creation of a printer-friendly model and the selection of materials to be employed during the procedure. It starts with a tissue biopsy, which creates a biological model that will be recreated using the 3D bioprinting method. This step involves the use of technologies such as computed tomography (CT) or magnetic resonance imaging (MRI) scans.
What are Bio-inks?
Bio-inks are biological materials used in the 3D bioprinting process to create engineered life tissues. It's a low-viscosity suspension biomaterial that can be put on a "bio paper" like a hydrogel substrate, culture dish, or polymer construct, among other things. The name "bio-ink" refers not only to the cells utilized in manufacturing but also to the carrier molecules that help the cells proliferate.
Bioprinting
The bio-ink is deposited in the printer to build a 3D structure in the second stage, which is the actual printing process. The bio-ink is then loaded onto a printer cartridge, which deposits the material based on the digital model created. The deposition of bio ink onto the scaffold in a layer-by-layer approach to building a 3D tissue structure is required for the creation of biological constructions. This step of the bioprinting process is complicated since it necessitates the production of several cell types depending on the tissues and organs to be created.
Post Bioprinting
Postbioprinting is the final phase in the bioprinting process, and it's crucial for the printed structure's stability. In the absence of this phase, the material's mechanical structure may be disrupted, affecting the material's functionality. Physical and chemical stimulations are essential to maintain the structure and function of living matter. These stimulations send messages to the cells, causing them to rearrange and maintain tissue growth.
Technology for 3D Bioprinting (Types)
Extrusion based Bioprinting
The most prevalent method of printing non-biological 3D objects is extrusion-based Bioprinting, also known as microextrusion. This bioprinting technology is used in tissue and organ research at a number of academic institutes.
It is the most widely utilized approach for producing pharmaceutical dosage forms due to its process flexibility and material availability.
Inkjet based Bioprinting
The most widely utilized technology for both non-biological and biological applications is inkjet bioprinting, also known as drop-on-demand Bioprinting. Originally, this technology was solely used for 2D ink-based printing, but it was later updated by replacing the ink in the cartridge with biological material and replacing the paper with an electronically controlled elevator stage to give control. Bioprinters that are custom-designed to handle and print biological materials with high precision, speed, and resolution can currently perform inkjet bioprinting.
Pressure-Assisted Bioprinting (PAB)
The ejection of biomaterials out of the printer's nozzle to build a 3D biological structure is the basis of pressure-assisted Bioprinting. Hydrogels, cells and proteins, ceramic material solutions, collagen and chitosan, and other biomaterials are commonly employed in this procedure. The printers' speed remains modest, and cell viability ranges from 40 to 80 percent.
Laser-Assisted Bioprinting (LAB)
The method of depositing biomaterials onto a surface utilizing a laser as a source of energy is known as laser-assisted Bioprinting. This approach was originally only used to transfer metals, but it has now been modified to work with biological materials such as cells, DNA, and peptides. A pulsed laser beam, a focusing mechanism, a ribbon with donor transport support, and a layer of biological material prepared in a liquid solution with a receiving substrate facing the projector make up a laser-assisted bioprinter. A hydrogel, culture media, cells, proteins, and ceramic materials are among the biomaterials that will be employed in laser-assisted Bioprinting. The bioprinters work at a medium pace, and the process preserves roughly 95% of cell viability.
Stereolithography (STL)
Stereolithography is a nozzle-free, freeform process for creating the three-dimensional structure of living and non-biological materials. The stereolithography technology provides the highest fabrication precision and may be utilized with a wide range of materials. The method employs light-sensitive hydrogels that are placed layer by layer to create a three-dimensional structure. This approach is extremely rapid (about 40,000 mm/s) and has cell viability of over 90%.
Applications of 3D Bioprinting
3D printers are already being used to make jewellery, apparel, toys, prototypes, camera cases, medical implants, and high-end manufactured things, to name a few.
Tissue Engineering
One of the most well-known uses of 3D Bioprinting is tissue engineering. It allows for the creation of complex tissues and organs that can be used to replace tissues that have failed or been lost.
Integration of the vascular network of arteries and veins and the inclusion of diverse cell types to generate complicated organ biology are difficult to achieve in the production of functional tissues and organs at clinically relevant dimensions. Despite this, many tissues have been successfully bioprinted while retaining their mechanical integrity and functionality.
Drug Development/Screening
Drug discovery is a time-consuming and expensive process requiring a significant financial and human resource investment. As a result, developing a technique to improve the ability to anticipate the efficacy and toxicity of newly produced medications earlier in the drug discovery process saves time and money. Bioprinting can create 3D tissue models that look like genuine tissue and can be used in high-throughput tests. The most popular tissues used to construct tissue models for drugs are liver and tumour tissues.
Toxicology Screening
The process of finding potential detrimental effects of chemicals on people or the environment is known as toxicology screening or testing. Pharmaceutical substances, cosmetic ingredients, home chemicals, and industrial chemicals are examples of chemicals. Some studies investigating the toxicity of certain compounds may necessitate a higher number of human participants with different metabolisms, which may appear unethical. Animals can be used in some research. However, they may not be able to accurately or reliably anticipate human responses. Instead, 3D Bioprinting may be used to create structures that imitate the form and function of human tissues in a highly automated and advanced manner. Real-time monitoring and high-throughput screening of diverse compounds are made easier with the usage of such structures.
Tissue Model for Cancer Research
2D tumor models have been utilized in cancer research for a long time, but they do not accurately depict the physiologically relevant environment because they lack cell-cell interactions. 3D bioprinting, on the other hand, enables accurate simulation of the disease microenvironment to investigate cancer development and spread. With a spatially mediated microenvironment and controlled cell density and cell-cell distance, many cell types can be bioprinted simultaneously to construct multicellular structures in a repeatable manner. HeLa cells can be bioprinted in a gelatin-alginate composite hydrogel to explore cell aggregation. These tissues can be utilized to research cancer progression and tissue structure and function changes throughout time.
Patent Analysis - Bioprinting
The country that remained on the top is the USA with 412 patents, followed by China with 405. Canada ranks third with 132 patents filed in its territory while Australia is fourth with 114 patents. India is positioned at the fifth spot with 69 patents. The only reason for this trend can be that the USA invests a lot in R&D in the medical and science sector as compared to most other countries. The other countries also seem to take hints and have started boosting growth in the sector.
Top Patent Assignees - Bioprinting
Thirty-two per cent market share is owned by the top 10 players in the industry. With over 1615 patents in the domain, Organovo has the highest number of patents filed under its name. Sichuan Revotek Biotechnology ranks second with 74 patents and Cellink thirds with 55 patents. The University of Missouri secures the fourth rank with 47 patent applications. Revotek is fifth with 41 patents. Aspect Biosystems, Anthrogenesis, Wake Forest University Health Sciences and Advanced Solutions Life Sciences rank sixth, seventh, eighth and ninth with 35, 29, 25 and 25 patents, respectively. Rokit Healthcare bags the last spot with just 23 patent applications.
Patent Filing Trend - Bioprinting
The first three years saw steady growth, with the patent numbers increasing gradually (34, 40, and 70). The fourth year saw a sudden spike in patent filings with a record of 184 patent applications. A dip was observed in the fifth year, with the number coming down to 163. However, the momentum was gained back quickly, and again positive growth trend was observed with the records showing 193, 244 and 308 patent applications in consecutive three years. In the ninth and tenth years, the numbers fell to 218 and 95, respectively. The fall can be explained by the costs of conventional and commercially available 3D bioprinting technology ranging between tens of thousands to several hundreds of thousands of dollars, strongly limiting its applicability to a small number of specialized laboratories. Also, the market acceptance and the customers' perception of the products or the 'prints' is largely unclear.
3D Bioprinting's Limitations and Future Challenges
Bioinks with good biocompatibility and mechanical strength are the key hurdles in Bioprinting. The present bioprinter technology has a lesser resolution and speed than previous generations, posing a hurdle for future improvement. Similarly, bioprinters should be able to work with a variety of biomaterials. Because the current speed of the bioprinting technique is modest, it should be enhanced to mass-produce biomaterials at a commercially acceptable level.
Tissue construct vascularization is a significant hurdle in 3D Bioprinting since tissues demand constant oxygen and nutrients. 3D Bioprinting raises certain ethical concerns, as the method's high cost may make it unavailable to the poor. Bioprinting of completely functional complex internal organs (such as hearts, kidneys, and livers) is still at least ten years away, if not more, but progress is being made rapidly.
References
https://www.azom.com/article.aspx?ArticleID=16892
https://www.frontiersin.org/articles/10.3389/fmech.2020.589171/full
https://en.wikipedia.org/wiki/3D_bioprinting
https://www.allevi3d.com/what-is-3d-bioprinting/
https://www.frontiersin.org/articles/10.3389/fbioe.2019.00184/full
https://www.3dbiology.com/3d-printing-organs-cost/
https://www.sciencedirect.com/topics/materials-science/3d-bioprinting
https://www.sigmaaldrich.com/IN/en/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/3d-cell-culture/3d-bioprinting-bioinks
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