General Perspective on the Function, Material, Development, and Applicability of Bio-Printers

Authors: Arda Bulut — Mehmet Eren Erken — Sarp Emre Turan

A. INTRODUCTION

The lack of compatible organs and tissues to use in transplantations and laboratory research has always been an issue in biological sciences. In organ and tissue transplantations, it is crucial to facilitate a rate of similarity between the donated material and the recipient’s original components.² Antigens are substances which grant cells identity and can create an immune response through their interactions with the receptors found on the surfaces of white blood cells.¹ A moderate to over activation of the immune response in the recipient vessel during transplantation procedures may result in acute organ or tissue rejection.² Because of this, any transferred solid organ or tissue should match with all six primary histocompatibility agents.² It has been shown by Smith et al. that an increased number of correlations within human leukocyte antigen (HLA) matching, between the donor and the recipient, reduced the magnitude of the immune response greatly.² However, finding the ideal match of HLA among donors for a given recipient may prove to be difficult as antigens can vary among different subjects.¹ To combat this many immunosuppressant agents such as corticosteroids, azathioprine, mycophenolate, cyclosporine, tacrolimus, antilymphocyte sera and rapamycin have been used widely in the treatment of transplant patients.³ However, long term use of calcineurin inhibitors and these immunosuppressants showed threatening side effects, one of which is nephrotoxicity.³ Similarly, in laboratory research, it is very crucial to obtain vessels of pristine condition to conduct experiments on. However, this may not always be the case as desired material or quality may not be acquirable at a given time. When faced with such insufficiencies, researchers have found the solution in creating the desired material from artificial 3D constructs. In this paper, the historical path of bio-printers, their fundamental working principles, the types of biomaterial they use, their limitations and possible improvements to the techniques have been discussed and summarized.

B. HISTORICAL DEVELOPMENT OF BIO-PRINTERS

To combat the issues of tissue individualization, and direct adaptation of tissue and organs, the first bioprinters were introduced in 1983 by Charles Hull who was the researcher to patent the stereolithographic method of 3D printing.⁴ After Charles Hull, Emmanuel Sachs was the first researcher to ever use a 3D printer with materials such as plastic, ceramic and metal.⁵ Following these improvements, in 1996, the first ever biomaterial was used in a printer to assist in tissue regeneration.⁴ It was considered to be a breakthrough when in 2001, the first bladder constructs and cell seedings were generated through the scaffold based printing technology.⁴ In the upcoming years of 2002 and 2003, researchers came up with a new method of bioprinting which was capable of characterizing cells through their viability.⁴ It was at this time that researcher Thomas Boland came up with the method of inkjet printing and elevated the pre-existing printing technology significantly.⁶ Using this newly acquired technology, professionals were able to synthesize tissue directly without any scaffold intermediates.⁷ The bio-printing technology was constantly worked and developed to points at which laboratories can print scaffold-free vascular constructs, skin, hepatocytes, articular cartilage, liver tissue, pancreas tissue and functional heart valves.⁷ Bioprinters were also tested to print and construct stem cells. However, as Ong et al. describes in their perspectives, a completely successful method as to the printing of mesenchymal stem cells and their seeding has not yet been established.⁸ The use of bio-printers in stem cell research is still experimented on as to the technique that is to be applied and the type of required biomaterial to carry out the printing process.⁸

C. BASIC PRINCIPLES OF BIOPRINTERS AND INTRODUCTION TO VARIOUS TECHNIQUES

The working principle of bioprinters is quite similar to that of the conventional 3D printers. Conventional 3D printing and Bioprinting resemble each other in two key concepts which concern the type of materials used in the application of the technique and the building phase of the product. Bioprinting is an additive manufacturing process where biomaterials such as cells and growth factors are combined to create tissue-like structures that imitate natural tissues or organs.⁹ This method forms organs and tissues in a layer-wise fashion by using a distinct reagent named “bio-ink” and combining it with the pre-existing 3D printing technology. Bio-ink can be described as filaments of bioprinters.¹⁰ Just as some objects are created by filament layers in the 3D technique, bio-inks are the main structures of layers that will turn into biologic structures such as tissues. It can be composed of just cells, but in most cases, an additional carrier material that envelops the cells is also added. Bioprinters’ working process can be divided into 3 key steps: Pre-bioprinting, bioprinting, and post bioprinting.¹¹

D. INTRODUCTION TO TRENDS IN BIO-MATERIALS

Materials used in bioprinters differ in a very large scale from types of collagens to artificial silks.¹⁶ These reagents are collectively named as bioink and the bioprinters may require different types of bioink depending on the composition of the extracellular matrix.

E. CRITIQUE OF TECHNICAL LIMITATIONS AND POSSIBLE IMPROVEMENTS

Although various developments and breakthroughs were achieved in the last twenty years, the field of bioprinting is still in search of new approaches that are capable of optimizing different aspects of the procedure to yield better quality compounds and negate any possible risks. These reconceptions mainly aim to minimize cell damage throughout their cultivation and improve the tissue manufacturing process.²²

F. REFERENCES

[1] Delves, P., 2021. Overview of the Immune System — Immune Disorders — MSD Manual Consumer Version. [online] MSD Manual Consumer Version. Available at: <https://www.merckmanuals.com/home/immune-disorders/biology-of-the-immune-system/overview-of-the-immune-system#:~:text=Antigens%20are%20any%20substances%20that,immune%20response%20in%20the%20body.>

Koç Üniversitesi Bilim Kulübü Resmi Medium Hesabı | Official Medium Account of Koç University Science Club