How India is building its 3D bioprinting industry

Since India amended its 2019 New Drugs and Clinical Trial Rules in March 2023, researchers have been able to use alternative methods to test the safety and effectiveness of new drugs.

Researchers expect a shift away from animal testing for drugs, as happened when similar changes to the law were made in the European Union and the United States. The amendment may boost 3D bioprinting which is being developed in laboratories and start-ups that have sprung up in India in recent years.

3D bioprinting allows living cells and biomaterials to be ‘printed’ layer by layer to mimic cell architecture in the body. Bioprints are used in pharmaceutical drug testing or to build tissues or organs to repair or replace damaged ones.

Bengaluru-based Pandorum Technologies is developing bioengineered ‘liquid corneas’ that can regenerate human corneas. Arun Chandru, co-founder of the start-up, says the 2023 amendment allows the team to use 3D bioprinted tissues to replace several cumbersome preclinical or animal studies. Contract research organizations are conducting preclinical drug tests on its 3D bioprinted corneas, and Chandru says the “less stringent scenario” has brought in additional revenue allowing it to offset some of its research and development expenses.

Biomedical engineer Falguni Pati, who heads the Biofabrication and Tissue Engineering Lab at the Indian Institute of Technology (IIT) Hyderabad, has developed various tissue models. He says that the amendment to the law will allow models to translate faster to industry.

The industry is set to grow with the global 3D bioprinting market valued at US$1.3 billion in 2022, according to a report by Emergen Research, and estimated to be worth US$8.64 billion by 2032. In December 2022, Indian Institute of Science (IISc) in Bengaluru opened the first 3D bioprinting Centre of Excellence in partnership with Swedish bioprinters CELLINK, which focuses research on the heart, bone, cartilage and cancer.

Specialized biomaterials

3D bioprints are created from scaffolding biomaterials called ‘bioink’ made of a polymer, living cells and components that aid cell growth. Avay Biosciences, a commercial start-up based in Bengaluru that manufactures 3D bioprinters makes four common bioprinting polymers: alginate, gelatin methacryloyl, agarose and pluronics. It is trying to develop collagen-based biomaterials at an affordable price for the Indian market, says its chief operating officer Suhridh Sundaram. Collagen extraction and purification from animal byproducts is an expensive process.

At the Biomaterials and Tissue Engineering Laboratory in IIT Guwahati, a team led by materials scientist Biman Mandal has been developing disease models to test drugs and creating tissues and organs for transplants in humans. Mandal’s lab uses Indian silk as a biopolymer, as it is 20 times cheaper than purified collagen. Its unique biological properties provide specific sites where cells can proliferate. A popular silk variety – mulberry silk – from northeast India has been approved by the US Food and Drug Administration for use in human transplantations.

The team has created eight different bioinks to produce bioprinted bone, cartilage, liver, pancreas and skin tissues.

“The cells require a specific environment, growth factors and the physical niche, which these bioinks provide,” Mandal says. For its bone bioink, additives such as hydroxyapatite were added to silk, to aid bone regeneration. β-D galactose is added to its liver bioink to aid liver cell attachment.

At IIT Hyderabad, Falguni Pati and his team are creating tissue-specific bioinks for the cornea, oesophagus, skin and liver. The process involves separating cells from tissues collected from humans or animals and using the extracellular matrix to prepare a hydrogel. The cellular response and function of such bioprinted tissues is superior to biomaterials such as collagen or gelatin, Pati says.

Pati’s lab has developed a 3D bioprinted cornea to replace cadaveric corneas in corneal transplants. To prepare the bioink, they collect the extracellular matrix from cadaveric corneas that are unsuitable for transplant.

For its liquid cornea, Pandorum formulated a hydrogel that mimics various properties of the cornea such as transparency and refractive index. The hydrogel is composed of a variant of hyaluronic acid and collagen that is modified to enable photo-crosslinking under visible light. More importantly, it contains nanosomes secreted by stem cells in the hydrogel to make it bioactive and promote tissue regeneration, says Chandru.

Lab to industry

Many of these models are expected to translate to industry in the next few years. Pati expects the skin and cornea models to be ready for drug and toxicity screening within a year. The team is establishing Good Manufacturing Practice protocols for their 3D bioprinted cornea and hopes to start clinical trials in two years.

Mandal’s lab intends to commercialize their skin, cancer tumour, liver and osteoarthritis models in the next two to three years. He foresees a longer gestation for the transplant grafts.

Pharmaceutical companies are already using Pandorum’s 3D human liver micro-tissues to test drugs, Chandru says. Meanwhile, the company is hoping to get approval from the Drugs Controller General of India and the US Food and Drug Administration to conduct the first-in-human clinical studies for its liquid cornea KuragenX.