Bioprinting is an additive manufacturing technology that utilizes a digital file as a blueprint to print objects layer by layer. Unlike traditional 3D printing, bioprinters use cells and biomaterials to produce organ-like structures that allow living cells to proliferate. Although bioprinting is a new technique, it has immense potential in advancing fields such as drug development, aesthetics, and regenerative medicine and personalized healthcare. Essentially, bioprinting is a type of 3D printing that can potentially produce anything from bone tissue and blood vessels to living tissues facilitating various medical applications, including tissue engineering and drug testing and development. The bioprinting process consists of three main steps:
Bioinks in Bioprinting
Biomaterials can be either synthetic or natural, or even a combination of both. In some cases, cell aggregates alone can serve as bioink for bioprinting procedures. Bioinks commonly consist of biomaterials such as hydrogels, cells, cell aggregates, or their combinations. Natural polymers like alginate and artificial polymers like gelatin are examples of materials used as bioinks. For the bioprinted tissues and organs to function properly, the ideal bioink must have the right mechanical, rheological, and biological qualities that can mimic the target tissues. Bioprintability, high mechanical integrity and stability, insolubility in cell culture media, biodegradability at a pace suited to the regenerating tissue, non-toxicity and non-immunogenicity, viscoelasticity, and the capacity to stimulate cell adhesion are few significant characteristics of an excellent bioink material. Additionally, bioink materials should be inexpensive, simple to produce and process, and readily available in the market. The ideal properties of bioink have been shown in Exhibit 1.
Applications of Bioprinting
Biocompatible materials are currently being developed for the biomedical industry offering significant advancements like the 4D bio-printing that possesses the form-changing properties of biomaterials and tissue-constructed structures. This innovative technology has diverse applications, including tissue engineering, drug delivery, and functioning organs. The impactful solutions bioprinting offers in healthcare and regenerative medicine include:
In general, bioprinting involves the precise layer-by-layer placement of biological components, biochemicals, and living cells to spatially control the arrangement of functional components within fabricated 3D structures. There are three fundamental approaches to bioprinting, which are summarized below:
Challenges and available solutions in Bioprinting
With advancements in printing technology and the development of efficient and cost-effective printing methods, the need for stringent quality control standards throughout the bioprinting process has become necessary but challenging. One of the key challenges in bioprinting is ensuring quality control standards at each step of the process, including model design, bioink selection, printing validation, post-printing maturation, and product quality assessment. Regulating these standards can be difficult but is crucial for successful transplantation outcomes. Another significant challenge lies in the complexity of the bioprinting process, which involves multiple components. The lack of software to define the placements of cells, biomaterials, and biological molecules virtually following the robust designing and translation that drive downstream manufacturing operations hampers the bioprinting process. Some common challenges on the road to bioprinting are presented in Exhibit 2.
To address the challenges mentioned above, several solutions have been proposed and developed in the field of bioprinting.
Limited options for biomaterials:
Vascularization of organs:
Recent Advancements in Bioprinting
Bioprinting has made significant strides in recent years, leading to successful transplantation of printed organs.
To achieve a competitive advantage, major players are concentrating on research and development to innovate new applications. For instance, CELLINK introduced the most sophisticated bioprinting tool, Bio X6 as well as Lumen X which specializes in creating vascular structures. Companies are joining forces and making acquisitions, partnerships, and mergers to increase their application portfolio, production capabilities, and competitive difference. For instance, BASF GmbH’s acquisition of the 3D printing company Sculpteo is expected to enhance their competitiveness and accelerate the development of new industrial bioprinting materials. The recent developments in bioprinting by select key players are shown in Exhibit 3.
Future Scope of Bioprinting
Bioprinting still has a long way to go before it can be used in a clinical context, especially in situ direct applications. Future research is now focusing on integrating different procedures to complement each other and improve the creation of tissue-mimicking structures. Applications for bioprinting, such as skin regeneration, cell and molecule delivery systems, and disease modelling, may be readily and easily available soon and enhance patient outcomes. These applications may transform how skin wound healing can occur faster. As bioprinting continues to progress, it will become increasingly feasible to print organ patches, complete replacement organs, as well as skin and bone grafts using a patient’s own cells. The use of bioprinting will empower medical professionals and researchers with the tools they need to better focus on therapies and enhance patient outcomes as personalized and regenerative medicine gain popularity.
In the future, key areas of research will include the development of novel bioprinting materials with superior biocompatibility, improved printability, and suitable mechanical properties. Focus on the creation of heterogeneous and gradient composite materials, the creation of biomaterials suitable for in situ bioprinting, the enhancement of the biological properties of materials using biomimetics or recombination with bioactive factors, and more will also accelerate. As the range of printing materials expands and their performance improves, bioprinting is expected to bring significant advancements to the field of healthcare technology.
Tissue and organ regeneration through bioprinting holds immense promise for additive manufacturing. It enables the creation of physiologically comparable tissue that gives patients better and more reliable functional results. Bioprinting techniques offer high-throughput tissue printing with precise spatial control and accurate cell patterning. In the US alone, there are over 120,000 people on organ waiting lists, and many more suffer from chronic conditions because of the long-term negative effects of post-transplant immunosuppression. Bioprinting is a revolutionary recent technology that has the potential to end the waiting list for organ transplants. Because bioprinting develops tissue from the ground up, there is less chance of immunological graft rejections, which help to alleviate the problems associated with donor shortage.
In the production of medicinal drugs, bioprinting offers provides a faster, cost-effective, and biologically relevant alternative to animal testing for drug efficacy evaluation. The field of medicine has seen major advancements because of bioprinting, including enhanced drug delivery systems and sugar stents for easier vein anastomosis during surgeries. Although bioprinting is still in its developmental stage and faces significant challenges, especially in terms of in situ applications, it is a rapidly evolving field with the potential to revolutionize modern medicine and healthcare. By overcoming hurdles and advancing bioprinting technologies, we can envision a future healthcare landscape where customized tissues, organs, and pharmaceuticals are readily available, enhancing patient well-being.
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