3D-printing with silk to treat knee injuries

Sindhu M

Researchers from the Indian Institute of Technology Guwahati (IITG) and West Bengal University of Animal and Fishery Sciences, Kolkata, have 3D printed knee meniscus with a new silk-based bio-ink that can be customised to the kneecap dimensions of the patient. This innovative approach paves the way to treating knee injuries in a patient-specific manner and minimising repetitions of invasive surgical procedures.

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3D bioprinted silk based meniscus. Photo credits: Biman B Mandal

The knee meniscus is a crescent-shaped fibrocartilage structure in the knee joint that acts as a shock absorber. Treating tears in the knee meniscus typically requires an open surgery. It may still be untreatable in the case of severe tears due to accidents or in chronic conditions such as osteoarthritis. An alternative solution is to 3D bioprint the knee meniscus tailored to the patient’s knee cap dimensions.

In a recent study, the research team led by Biman B. Mandal, a professor at the Indian Institute of Technology Guwahati (IITG), reported about engineering a custom bio-ink consisting of silk fibroin methacrylate, gelatin methacrylate, polyethylene glycol dimethacrylate to 3D bioprint the knee meniscus. Mandal says, 

This is a very unique combination of silk used in meniscal tissue engineering applications. India is popular for silk clothing, and the work done by the scientific community is also enabling the use of silk for various other tissue engineering applications.

The researchers used a combination of polymers that underwent chemical modification, enabling them to cross-link and solidify upon exposure to visible light. This process allows the bio-ink to remain gel-like during the printing process and to cross-link later for application as knee meniscus. The bio-ink also contained stem cells isolated from human platelet-rich plasma needed for the growth of stem cells seeded on them. These seeded stem cells matured into fibrochondrocytes, which are dominant type of cells in the knee meniscus tissue. They produced extracellular matrix of the knee meniscus to heal it. 

Biman B Mandal and Ashutosh Bandyopadhyay. Photo credits: Biman B Mandal
Biman B Mandal and Ashutosh Bandyopadhyay. Photo credits: Biman B Mandal

Bikramjit Basu, a professor at the Indian Institute of Science (IISc) in Bangalore and an expert in engineering ceramics, who was not associated with the study, comments on the challenging nature of the research. Basu says, 

Layer-by-layer fabrication of bio-ink, which contains cells, proteins, and other biological molecules in silk-based biomaterials, is a challenging task, but the authors have succeeded in it.

Besides being suitable as a 3D printing ink, the biomaterial composition should have load-bearing capacity and be compatible with the immune system to be used as a knee meniscus. Therefore, researchers performed various tests, such as cyclic compression tests that mimic the knee strain, to ensure the mechanical suitability of the material for the knee meniscus application. Then, to check if the material is compatible with the immune system, they cultured immune cells on the 3D printed constructs using the bio-ink, observing no adverse immune response. To further confirm the immune compatible properties, researchers implanted the bio-ink construct under the rabbit skin and observed no adverse immune response. 

In this study, researchers have developed a material that can be 3D printed and used to treat knee meniscus tears. Unlike conventional methods based on surgery and removal of damaged tissue, this method can recruit the cells of the meniscus for healing and even recapitulate the intricate architecture of the tissue. 

The next step would be to create knee meniscus tears in animal models and use the 3D printed construct to heal the defect. Then, it can move forward to next phase of preclinical evaluations. After obtaining the necessary regulatory approvals, it can be used to treat meniscus injuries of humans in the future. Researchers envision that their bio-ink formulation will soon be used in clinics. 

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