When hip and knee surgery became popular from the 1960s onwards, surgeons and patients alike must have been so grateful for its life-changing potential to relieve chronic pain and give people back the movement and mobility they had lost in their damaged joints.
But now there are equally exciting developments as researchers in biomedical engineering seek to rejuvenate damaged cartilage and spinal discs with implantable or injectable biomaterials which train the body’s tissue to regenerate itself.
Daniel Kelly, professor of tissue engineering at Trinity College Dublin (TCD) and director of the Trinity Centre for Bioengineering, is one of the key researchers in this field in Ireland and indeed internationally.
And Cartregen is one of the current projects he is working on in collaboration with researchers at Queen’s University Belfast (QUB). For this Higher Education Authority-funded project, researchers at QUB, led by Dr Krishna Manda, have developed a computational model of a soft hydrogel to be implanted into articular cartilage in the knee joint to help it repair itself.
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“The current gold standard to treat cartilage damage and osteoarthritis is to replace the whole joint but the alternative is to develop a scaffolding system in the laboratory and grow implantable tissue to be placed on to it which has comparable mechanical properties to native tissue,” says Manda, who is based at the School of Mechanical and Aerospace Engineering at QUB.
Now, one year into the Cartregen project, researchers in biomedical engineering at TCD will test the strength of this new biomaterial to see if it will be able to withstand the biomechanical pressures of being implanted in a human knee joint. While the researchers are based in universities such as Trinity College Dublin and RCSI, a lot of their work is undertaken through funding and research from AMBER, the Science Foundation Ireland Research Centre for Advanced Materials and BioEngineering Research.
“The aim is to regenerate tissue at an earlier stage to stop the progression of the degeneration of the joint to prevent or delay the need for knee replacements,” Kelly says.
Some examples of these next-generation biomaterials already exist but, according to Kelly, they don’t yet consistently regenerate the novel structure of the specific type of healthy cartilage tissue which is required to keep the joint in good condition.
“We know that fibro-cartilage develops as injured tissue but the challenge is to get the body to develop the healthy cartilage tissue known as hyaline cartilage,” he says.
The aim is that these biomaterials will stay in the body for two to three years and then degrade as the body’s own tissue takes over the repair work. “We want to design materials to instruct cells to come into this material to make its own healthy tissue,” Kelly adds.
One of the key techniques that makes this research so striking is the use of very advanced 3D printing which allows the researchers to print very fine polymer fibres which are about a 10th of the diameter of a human hair.
“Once we can begin to print fine fibres similar to what you see in native human tissue, we can better replicate the mechanical properties and architecture of the articular cartilage – which is itself very well understood,” Kelly says.
Prof Conor Buckley, professor in biomedical engineering at TCD, is also working on a novel biomaterial which, if proven to work, could be injected into the disc of the lower back to treat back pain derived from herniated or damaged discs.
“This work started in 2020 with a European Research Council (ERC) funded Integrate project which has been investigating the micro-environment inside the disc to see how cells would respond if gene-activated biomaterials were injected into them,” Buckley says.
The aim is that by introducing injectable biomaterials into the damaged disc, the biochemical and biomechanical properties of the soft inner section of the disc can be regenerated.
Buckley has recently been awarded an ERC proof-of-concept award for the injectable biomimetic [materials which mimic human biochemical processes] hydrogel systems which will allow researchers progress to biomechanical testing, preclinical and commercial evaluation of these novel biomaterials.
“The significance of these biomaterials is that they can temporarily replace the soft, gelatinous core of the disc which loses its structure when it degenerates or penetrates out of the disc, pressing on a nerve root ending in the back and sometimes causing pain in the buttocks and leg,” he says. The novel biomaterial – which has yet to be tested on humans – also has adhesive properties which allow it to stick to native tissue in the intervertebral disc.
The next step for Altach is to manufacture these laboratory-derived materials under scalable conditions in a commercial clean room environment before advancing to human clinical trials
Currently, the only treatment for this specific type of lower back pain is surgery to remove part or all of a damaged/herniated disc in the lower spine (microdiscectomy) or spinal fusion. The latter involves the removal of the damaged disc so that vertebral bones can be fused together.
“The problem with spinal fusion is that it changes the biomechanical forces and starts to cause degeneration in other parts of the spine. The aim of these new therapies is to delay the need for such complex surgery,” explains says Prof Buckley, who is also an honorary associate professor in the Royal College of Surgeons of Ireland (RCSI).
In 2023, Buckley and Kelly raised €1.1 million in funding so that their campus company, Altach could begin the commercialisation process for an animal-derived matrix to treat osteochondral, a defect of the cartilage and bone.
“We use cartilage and bone from a pig and remove the cellular material to prevent an immune system response [ie rejection of the animal tissue]. Then we process this de-cellularised material into a bi-layered sponge to treat this condition. The bone/cartilage matrix retains the cues to tell human cells what to do,” Kelly adds.
The next step for Altach is to manufacture these laboratory-derived materials under scalable conditions in a commercial clean room environment before advancing to human clinical trials.
Prof Fergal O’Brien, professor of bioengineering and regenerative medicine and head of the tissue engineering research group at RCSI, has already had success bringing biomaterials to help bone repair from the laboratory to human patients.
“We are now working on biomaterials for the repair of peripheral nerves damaged by complex burns, for example,” he says. With this research project, Integra LifeSciences in New Jersey will develop the biomaterials for commercial use in humans.
O’Brien is also working in partnership with the Irish Rugby Football Union charitable trust on spinal cord injury research. “The exciting thing about this research is that we will use the biomaterial to deliver stem cells and gene therapies to native tissue.”
Overall, he says biomedical engineering researchers in Ireland are highly regarded around the world. “We were the guest nation at the Orthopaedic Research Society conference in Dallas, Texas, in 2023. University researchers need to work closely with industry partners and we do that very well here.”
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