Biomaterials
Despite these advances, researchers have struggled to design hydrogels for mechanically active tissues like the heart and vocal cords.
“New biomaterials are being developed every
day, which really show some potential in repairing wounded tissue,” says Guangyu Bao, a postdoctorate researcher in the Department of Mechanical Engineering at McGill University. “But in terms of the biomaterials being investigated right now, they’re being tested on tissues that are in a static condition, rather than a dynamic condition.”
Why this is so challenging? To take the vocal cords as an example of a dynamic condition, the area vibrates more than 100 times a second during speech, placing it under prolonged mechanical stress. While biological tissues are well equipped to withstand this stress, it is hard to design synthetic materials that are up to the task. “Biological tissues in general are very tough, which can usually prevent tissue damage under normal working conditions,” says Bao. “Most synthetic tissues are like jello. Their toughness is orders of magnitude lower than real biological tissues.”
Placed in a mechanically dynamic organ, most synthetic materials would simply break. We see that with the hydrogels that are currently used for vocal cord repair – patients need regular injections because the material is so short-lived.
On top of that, most biomaterials have a very small pore size. This gives rise to limited blood perfusion, which blocks oxygen and nutrients from reaching the area and can prove hostile to the surrounding cells. There is often a trade-off to be made between porosity (essential for blood perfusion) and mechanical strength. “There are definitely some methods to make the synthetic materials both tough and porous,” says Bao. “However, those methods are generally not compatible with injection, which is the preferred method in the clinic for minimally invasive treatments.”
Tackling porosity and toughness at the same time Together with his fellow researchers at McGill University, Bao has been working on a solution to these problems – a new injectable hydrogel that
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is both highly permeable and mechanically robust. One day, this hydrogel could be used to stimulate tissue repair in some of the most challenging environments of the body. “We believe this biomaterial really has the potential to solve the biggest challenges in regenerating mechanically active tissues,” says Bao. The multidisciplinary team, led by Professor Luc Mongeau and Assistant Professor Jianyu Li, began work in this field around four years ago when they designed a hydrogel based on chitosan. Derived from the shells of crustaceans, chitosan is biocompatible and can also be made to be porous. The resulting hydrogel was both injectable and well-suited to perfusion.
The schematics of a surgery performed on vocal cords using the hydrogel.
“We believe this biomaterial really has the potential to solve the biggest challenges in regenerating mechanically active tissues.”
“Around the same time, we also got to know a method called double network design, which is used to make biomaterials tough,” recalls Bao. “Unfortunately, this type of network design is really toxic in the body and doesn’t generate porous material. We got to thinking, maybe we could use the same design principle but using our biocompatible material. That would allow us to generate hydrogels that were both porous and tough.”
The researchers followed this line of enquiry, and were heartened to see positive results. Their new improved hydrogel combines two polymer networks – chitosan and another elastic polymer called glyso-chitosan. The result is a stretchy material that doesn’t easily break. What’s more, their technique could be easily adapted to work with alternative biomaterials like gelatin.
Because of the nature of chitosan, the pore size is 100 to 1000 times larger than most existing hydrogels – in other words, cell-sized as opposed to nano-sized pores. Meanwhile, its mechanical toughness is between eight and 40 times greater than standard biomaterials.
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McGill University
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