Can you imagine, a human body part being 3D printed for implantation? Scientists, all over the world, are untiringly working to make it real one day. The twenty-first century has seen the revolutionary development of 3D bioprinting, which offers immense hope in various medical applications, tissue engineering, and pharmaceutical research. It offers solutions to complex problems such as organ transplantation shortages and personalized healthcare.
Through this blog we are delving into the course of this innovative journey, the progress, and the real picture, which is going to loom large in the future.
History of 3D Bioprinting
The history of 3D bioprinting dates back to 1984, when Charles Hull found the stereolithography (creating 3-dimensional structures layer by layer using laser technology) method, laying the foundation for 3D bioprinting. This innovation has developed exponentially, evolving from creating resin models layer by layer to inventing outstanding projects in the medical world.
In 1988, Dr. Robert J. Klebe from the University of Texas presented bioprinting with an HP inkjet printer to print structures using cells via the cytoscribing method.
In the 90s, Dr. Gabor Forgacs, the founder of Organovo, recognized that cells could be combined into new three-dimensional structures. This led to the research on biomaterials, which revolutionized regenerative medicine. His findings guided scientific researchers to create structures using living cells.
In 1999, Wake Forest Institute for Regenerative Medicine embarked on designing the world’s first synthetic organ- a human bladder. It used a spatial scaffold to create the organ.
Professor Anthony Atala’s team used the recipient’s host cells to create the bladder to reduce the chances of organ rejection by the recipient’s body. The recipient, Luke Massella (a young boy) was fighting with a defective bladder and Atalala’s invention helped him live a normal life. Even after a decade of the implantation, he did not encounter any complications, attesting to the procedure’s success.
Nine other younger patients also received the 3D bladders. Later, Atala even created and presented a 3D kidney prototype at a TED conference.
In 2003, Thomas Boland and W. Cris Wilson Jr. modified an office inkjet printer to facilitate research in bioprinting with biological materials. Dr. Forgacs came forward with his version of the bioprinter in 2004, initiating 3D bioprinting with direct biodegradation necessitating no scaffolding.
In 2008, 3D-printed prosthetic limbs as a whole became a reality.
Dr. Forgacs’s Organovo launched a commercial bioprinter, NovoGen MMX, in 2009, facilitating the creation of the first biodegradable blood vessel, surpassing the need for the cell scaffold.
The decade commenced in 2010 witnessed an exponential surge in bioprinting advancements. The industry witnessed the birth of baptismal tissue (2012), liver (2012), tissues featuring blood-borne networks (2014), and heart valves (2016). These years were marked by intense research endeavors, striving to fabricate structures of increasing complexity and functionality, demonstrating the ceaseless potential of 3D bioprinting.
In 2018, the Indiana University School of Medicine (IUSM) was awarded around nine million to continue their research on 3D bioprinting of human organs.
In 2019, a miniature version of a fully functioning heart was made. The Warsaw Foundation created a prototype of a human pancreas.
In 2020, an American 3D bioprinting company, Advanced Development of Additive Manufacturing got the FDA clearance for bioprinting bones.
Even now, researches are going on relentlessly in the hope of creating human organs to help people who wait for years to get donors and die without getting one on time.
Understanding the Technology behind 3D Bioprinting
Before understanding the 3D bioprinting technology, we should know the basic steps in bioprinting. They are as follows:
Gathering the Necessary Data
The first step involves creating a 3D model, which is the blueprint for the bioprinting. This can be achieved through various techniques such as X-ray, CT scans, or MRI, to build a detailed representation of the structure that needs to be printed. Alternatively, CAD software can be utilized to establish the model from scratch. The model is then divided into 2D slices using special software, preparing it for bioprinting process.
Choosing the Right Materials
In this phase, careful selection of materials such as cells, growth factors, and hydrogels is vital. These materials, collectively known as bioinks, should satisfy specific requirements to ensure compatibility with the biological structure intended to be printed. The hydro-gel-based bioinks are created from water and nanofibrillar cellulose. The density and composition of the bioink also could affect the cell density and flexibility. Thus, the right choice of bioinks is crucial to secure biocompatibility, ease of printing, and suitable mechanical properties.
Before initiating the bioprinting, it’s necessary to set up the appropriate printing parameters to secure precision during the process. Constant monitoring is also essential to quickly address any issues that might arise, ensuring a smooth printing operation.
Bioprinting can be done in different methods- inkjet, laser, or extrusion-based. (See in detail in the blog)
Making it Functional
The final step is about bringing the printed structure to life by promoting cell connections and fostering functionalities similar to a natural tissue or organ. This is achieved through the careful application of physical and chemical stimulations to encourage cells to form connections and assume their intended functions, effectively giving rise to a viable biological structure.
Process of Bioprinting
Now, let’s delve into the pioneering work by Atala’s team in creating a human bladder using bioprinting, marking a milestone in medical science.
Initially, they obtained muscle cells and the cells from the inner lining of the patient’s bladder through a biopsy. These cells were then cultivated in a lab to increase their number to the desired level for bioprinting the bladder.
Next, a bioink, crafted specially for this purpose, was prepared by combining it with the developed cells. This concoction was loaded into the printer’s ink heads. Before this process, a 3D representation of the patient’s existing bladder was produced using radiography, serving as a guiding map for the printing process.
Drawing from the detailed blueprint acquired from the 3D image, a biodegradable scaffold resembling the bladder was crafted using the bioprinter with live human cells. This scaffold acted as a temporary framework that would eventually dissolve.
This frame was nurtured for around two months, allowing the cells to flourish and form a full-fledged organ. Following this growth phase, the next step was to transplant this newly crafted bladder into the patient.
An extraordinary feature of this process was the biodegradable nature of the scaffold, which disappeared once the new bladder tissues melded harmoniously with the patient’s body, fulfilling its role as a guide for the developing tissues.
Historically, bladder issues were solved using sections of the intestine, but this method had a fundamental flaw — it absorbed substances instead of expelling them, leading to severe health issues. This method was essentially forcing a tissue designed for absorption to carry out the opposite function.
The success of Atala’s approach lies in the utilization of actual bladder cells, eliminating the complications seen in the traditional method. Patients who were fortunate enough to receive this innovative treatment have been living complication-free for many years, showcasing the procedure’s long-term success.
Types of Bioprinting
Based on the principles, bioprinting can be classified into three types.
This is an affordable method with a great deposition and printing speed when compared to the other methods. It helps in high-density cell printing with lesser cell damage during the process. However, it could create only sizes over 100 μm. This is the most preferred 3D bioprinting methods for its affordability and versatility.
It is capable of creating precise tissue fabrications. As it is the nozzle-less method, it eliminates cell damage due to stress or nozzle clogging. It can create high-resolution structures even below 10 μm. The disadvantage of this method is that it can cause thermal or mechanical related cell damage, is highly expensive to set up, and lacks photocrosslinkable bioinks.
Inkjet or droplet-based
This technology can work with a high resolution of 10-50 μm with a high printing speed of up to 10,000 droplets. It has highly precise control over the creation of the scaffold. However, it cannot use high cell density bioinks as it can cause clogging. It is impossible to create 3D structures vertically in this method.
Challenges and Hurdles in 3D Bioprinting
- Replicates Precise Organic Structures
This technology is adept at perfectly mimicking the structures of specific tissues or organs, lending itself to more accurate and realistic models, which can be indispensable in the medical field.
- Will Transform Future Medical Treatments
3D bioprinting harbors the potential to usher in a revolutionary phase in medical treatments, setting the stage for advancements that are hard to understand today, thereby altering the course of medical science.
- Personalized Treatments for Individuals
It facilitates the creation of treatments specifically designed according to individual patient profiles and particular organs, introducing a new level of personalization in medical interventions, which could enhance treatment efficacy.
- Extreme Accuracy in Drug Testing
The technology promises to redefine drug testing by allowing a more detailed and precise examination of the efficacy of drugs, potentially steering the pharmaceutical world towards more successful and safe drug developments and testing.
- Reduction in Animal Testing
3D bioprinting can significantly diminish the reliance on animal testing, steering research methods towards a more ethical and humane pathway, thus protecting animal rights and ensuring accuracy in the drug’s effects on human beings.
- Enhanced Compatibility with Human Physiology
Structures created through 3D bioprinting demonstrate high compatibility with human cells and tissues, prophesying a future with higher success rates in organ transplant surgeries and various other treatments.
- Complex Medical Processes Made Simple
3D bioprinting technology automates intricate processes involved in medical production, enhancing efficiency and reducing the time taken to develop biological structures, which can be a pivotal change in emergency medical responses. It is anticipated that even physicians can print the needed body parts like bones for bone grafts at the time of surgery, depending on the need of the patient in a short time in the future.
- Reliable Outputs with Lesser Errors
Through the minimization of human intervention, 3D bioprinting ensures consistent results, reducing errors, and establishing a higher standard of reliability in the production of biological materials, securing a safer and more trustworthy foundation for medical advancements.
- Highly Expensive
Bioprinting organs or additive manufacturing would need highly expensive medical equipment, which could not be afforded even by the most profiting healthcare facilities in America. This would prompt them to stick to their conventional organ transplant methods like acquiring from donors.
- Complicated Process
Accumulating the biomaterials or other materials for printing would be challenging and hard to find. The cost of device maintenance would be pricey. The process of bioprinting is very complex as the human organs with the nebula-like vasculature could be very much challenging and any minor error could spoil all the hard work.
- Tough to Maintain Cell Environment
Maintaining the working temperature of the bioprinting is essential in maintaining the cells in a safer environment. If the bioprinter heats up during the process, the quality of the cells and the organ going to be constructed also will be affected. Any flaw during the process like using cells not genetically matching as the source or a low-quality organ can cause the body’s autoimmune response destroying the donated tissue.
- Ethical Issues
Treatment should be equal for all without the disparity between rich and poor. The expensive nature of bio-printed organs makes them accessible only to the elite and hard to reach for the poor. This relatively new type of treatment will have risks to as it has not proven to be 100% safe.
As we stand on the peak of further advancements, the path ahead promises unprecedented breakthroughs. The combined spirit of the scientific community, paired with relentless innovation, forecasts a future where 3D bioprinting becomes a cornerstone in personalized medicine, offering solutions previously deemed the world of science fiction.