Scientists use stem cells to 3D bioprint articular cartilage prostheses, which is expected to improve the treatment of athletes’ joint diseases

On September 27, 2021, scientists from Japan’s Saga University and Kyoto University’s Zhongshan Laboratory used stem cells to produce3D printingThe cartilage structure is expected to be used to repair large cartilage defects in related patients.Researchers use human induced pluripotent stem cells (iPSCs) and use scaffold-free KenzanbiologyThe printing process creates a cartilage structure, where the only supporting structure for the bio-ink is the microneedle matrix.According to reports, this technology of scientists overcomes the limitations of scaffold-based tissue engineering methods in creating cartilage-like structures, such as poor cell compatibility and toxicity, and at the same time solves the bacterial infection and problems associated with traditional joint prostheses. replaceOperationSome related risks.

The purpose of this research is to treat diseases such as arthritis in athletes who are unwilling to receive treatment for artificial joints made of metal and plastic.

△3D printingSchematic diagram of the process. Picture from Biofabrication.

Improve arthritis treatment

Articular cartilage is a weight-bearing connective tissue that covers the ends of bones to prevent friction and protect joints. Cartilage damage can occur due to disease, trauma, and degenerative conditions, such as osteoarthritis, which is one of the main causes of joint pain and inability to move.
More than 300 million people worldwide suffer from osteoarthritis, causing a huge
clinical
And financial burden.Current surgical treatments such as microfractures and
Implants
, Usually only focus on lesion defects and cannot produce durable functional cartilage. Total joint replacement is also the only treatment for advanced osteoarthritis. Implants lack durability over a long period of time, which may lead to bone shortening and other complications.

Tissue engineering is an alternative to total joint replacement for cartilage repair and joint protection. However, this method is limited by the lack of functional cell types and biomaterials. Chondrocytes and mesenchymal stem cells (MSCs) are currently considered to be the most promising sources of regenerative therapy cells, although they are hindered by donor age, density, viability, cell phenotype and other factors.

iPSCs are an alternative cell source and show promise in overcoming these limitations because their self-renewal potential can provide an almost unlimited number of pluripotent cells that can differentiate into many different cell types. Therefore, iPSCs were selected as the basis for scientists to build cartilage structure.

△biology3D printingmachineThe design data and the image of the L-shaped structure taken from Kenzan 18 days after printing. Picture from Biofabrication

3D printingCartilage development

The current tissue engineering technology used for cartilage regeneration can be largely divided into scaffold-based methods and scaffold-free methods.3D printingIt has also been used in many research projects in this field.
For example, scientists from Chalmers University of Technology have previously demonstrated the use of3D bioprintingTechnology to treat osteoarthritis cartilage tissue engineering, microbiologists at Central Queensland University explored crocodile protein and3D bioprintingThe feasibility of a combination of technologies to repair joint damage.Elsewhere, researchers at Penn State University have developed a novel3D printingMethod to create cartilage tissue components with micropores to allow nutrients and oxygen to diffuse.

Recently, researchers at the University of Alberta developed a3D bioprintingMethods: Customizing nasal cartilage for cancer patients with facial disfigurement after surgery. Swansea University, in cooperation with the Scarless Foundation, is carrying out a scarless ear and nose transplant.3D printingCartilage tissue scaffold.At present, progress has been made in this field, and the notable move is the EU-supported TRIANKLE project, which is being developed3D bioprintingThe cells repair ankle implants. Last year, the project was supported by the R&D laboratory of the Barcelona Football Club of Spain. The club has agreed to test collagen-based cell transplantation in its amateur team in order to finally prepare for future commercial releases.

△biology3D printingThe design data of the machine and the image of the tubular cartilage structure. Picture from Biofabrication.

IPSCs 3D printingCartilage scaffold

Japanese scientists’ current research purpose is to use3D bioprintingMachine to design a scaffold-free cartilage structure of anatomical size and shape. The study used Cyfuse biological
medicine
The company’s Regenova Bio-3D printingmachine. Regenova is a new type of robotic system that completes the manufacture of three-dimensional cell structures based on pre-designed three-dimensional data by placing cell spheroids in a fine needle array, the Kenzan method.

The Regenova printer uses a 9×9 square Kenzan array composed of 81 needles, a 26×26 square Kenzan array composed of 676 needles, and a circular Kenzan array composed of 36 needles with a diameter of 7 mm.3D printingCartilage originals in various sizes.First, iPSCs are induced to differentiate into chondrocytes (metabolic active cells for cartilage formation) through MSC, forming highly chondrogenic and effective iNCMSCs. Then the bioprinting process was optimized for iNCMSCs, and then the shortest maturity period was determined. The various types of Kenzan listed above are used to make larger cartilage structures that are specifically designed for irregular defects.

The first construct demonstrated the potential of the method to maintain shape and was printed in a 90-degree L shape. After being removed from Kenzan, the structure can maintain the applied design and can withstand mechanical operations, even though its total area is only 2cm2.With the 7mm circular Kenzan array combination, the scientists were able to increase the size of the construct to a 6cm square semi-tubular structure, which can be used to treat a wide curved area, such as the surface of the patella.

△biology3D printingThe design data of the machine and the image of the shape and structure of the articular surface. Picture from Biofabrication.

Through their methods, scientists can successfully3D printingA stent-free, self-sustainable cartilage structure of suitable size and shape can be used to repair larger cartilage defects. The researchers also found that the strength of these constructs is almost the same as that of normal cartilage.Scientists will continue to evaluate the durability of the cell-based joint prosthesis in future studies, and hope that it can solve the bacterial infection problems of traditional joint prostheses and some of the risks associated with replacement surgery. However, they also pointed out that although using iPSC-derived cells as a source material has many benefits, it is still very expensive. Therefore, they said that further optimization and improvement of the technology will be the key before conducting more time- and money-consuming in vitro studies.

More information about this research can be found in the paper titled “Bio-3D printing iPSC-derived human chondrocytes for articularcartilage regeneration” published in the journal Biofabrication. The co-authors of the study are A. Nakamura, D. Murata, R. Fujimoto, S. Tamaki, S. Nagata, M. Ikeya, J. Toguchida, and K. Nakayama.

Links to related papers:https://iopscience.iop.org/article/10.1088/1758-5090/ac1c99

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Scientists use stem cells to 3D bioprint articular cartilage prostheses, which is expected to improve the treatment of athletes’ joint diseases

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