Dec 20, 2018 | By Cameron

The race to 3D print bone is on, with entrants from around the world. A team of Indian researchers from Indian Institute of Technology (IIT) Delhi and IIT Kanpur recently pulled ahead with a breakthrough involving 3D printed cartilage that then becomes bone with the addition of thyroid hormones. The discovery will surely accelerate the development of bioprinting technologies and techniques.

Bone is formed in two ways. For non-load-bearing bones like the skull, mesenchymal stem cells differentiate directly into bone cells. For load-bearing bones such as femurs, the stem cells first differentiate into a cartilage template that then over time undergoes more differentiation into bone cells. Thus far, attempts to create load-bearing bones using scaffolds have differentiated stem cells directly into bone cells, skipping the cartilage phase that occurs naturally in our bodies. “The efficacy of such bone constructs is yet to be demonstrated in bearing loads. There is very poor correlation between bone constructs developed in vitro and in vivo. Also, gene expression pattern of these tissue-engineered bones largely differ from human adult bone,” commented Professor Sourabh Ghosh from the Department of Textile Technology at IIT Delhi.

The team decided to mimic the cartilage step by 3D bioprinting a cartilage scaffold that was then treated with a thyroid hormone (Triiodothyronine or T3) that triggers the differentiation of cartilage into bone-like cells. Their 3D printed bone exhibits gene and protein expressions similar to those found in naturally occurring bone, and necessary cellular signaling pathways for osteogenic differentiation are also upregulated. “When we followed a different strategy to develop bone there is more similarity to limb skeleton development in vivo,” said Professor Ghosh.

The cartilage scaffold provided a suitable substrate for what would become the extracellular matrix of the bone. Professor Amitabha Bandyopadhyay from the Department of Biological Sciences and Bioengineering at IIT Kanpur explains, “The load-bearing capacity of a bone depends primarily on the quality of extracellular matrix. In loading-bearing bones, the extracellular matrix comprises 95% while bone cells are just 5%. So if you are trying to fabricate a load-bearing bone construct it is better to have more extracellular matrix. Compared to bone formed directly from stem cells, the extracellular matrix of the bone construct developed through the intermediate cartilage process was 10s of times higher.”

The mesenchymal stem cell-to-cartilage phase takes about three weeks and the cartilage-to-bone step takes another two weeks. While the study doesn’t investigate the mechanical properties of the 3D printed bone, Professor Ghosh said their preliminary tests show it to be stronger than bones differentiated directly from stem cells. Thanks to advances like this, it’s possible that 3D printed bone graphs and patches for repairing extensive breaks will be in use in as little as five years. That’s great news for professional athletes and clumsy people alike.



Posted in 3D Printing Application



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