Engineering the future of bone technology
An interview with Fergal O’Brien, Professor of Bioengineering & Regenerative Medicine, Deputy Director of Research and Head of Tissue Engineering Research Group in Royal College of Surgeons in Ireland, Royal College of Surgeons in Ireland
Q: OPN: Tell us a little about your background and education and why the orthopaedics industry appealed to you.
A: FO’B: My background is quite interesting as I am an engineer by training but spend most of my time in a medical school. I am a graduate in mechanical engineering from Trinity College in Dublin and following that I did a PhD that crossed over between the Royal College of Surgeons (Ireland) and its medical school and the engineering school in Trinity College. I worked in the area of bone fracture mechanics and mechanobiology, so while some of my engineering friends were working on why metal components and aircraft components broke, I was looking at the mechanics by which bones break. I then moved to Boston, USA, and once again I crossed over between an engineering school at MIT (Massachusetts Institute of Technology) and Harvard Medical School. That is when I began to work in the area of tissue engineering, becoming upskilled in the development of technologies for regenerative medicine applications. When I returned to Ireland I was appointed as a lecturer in anatomy, I believe I am the first engineer in Ireland ever to be a medical lecturer. I now teach human anatomy in Ireland’s largest medical school at the Royal College of Surgeons in Ireland, but I also have an adjunct position at Trinity College in the engineering school, so I am Professor of Bioengineering and Regenerative Medicine in the Royal College of Surgeons in Ireland and adjunct Professor of Bioengineering at Trinity College Dublin.
Q: OPN: In the last issue of OPN we featured a news story about the organic bio-foam patch that regenerates bone and cartilage. Could you explain more about how you developed this bone-grafting technology and how it works?
A: FO’B: The role of tissue engineering is to develop cell and biomaterial-based strategies to restore the structure and functional properties of damaged or regenerated tissues and the focus of our group here in Dublin, in which I head a group of about 40 researchers, is to use natural based biomaterials as a platform for tissue regeneration. The particular patches for bone and cartilage are very much based on the components of what is found in the native tissues. One material, that we call HydroxyColl, is a collagen hydroxyapatite scaffold. Collagen is the most common protein found in the body – in multiple tissues and organs. It gives bone its tensile strength. However, it is soft and what makes bone stiff is a ceramic, known as hydroxyapatite. Collagen is a natural biopolymer, while hydroxyapatite is the ceramic mineral found in naturally occurring bone tissue. Our material is a highly porous material that consists of collagen and hydroxyapatite and when it is implanted into the body it provides cues to the body’s own cells to lay down bone tissue. It is really a bone graft substitute. HydroxyColl is capable of directing bone regeneration while supporting the body’s own natural healing process and is completely replaced by newly formed, healthy bone tissue. The cartilage repair technology, ChondroColl, developed from this. As we had managed to develop a product that was extremely good at regenerating bone, we then looked at cartilage (the adjacent tissue to bone in articular joints). The problem with cartilage is it does not have a blood supply and it does not regenerate. So if you get damaged cartilage it can lead to arthritis and it can lead to a requirement for joint replacements. The way our technology works is if a patient has a damaged site on a knee or a hip, the surgeon would come in and drill a hole down as far as the bone marrow, the surgeon would then place our patch, or scaffold, into the void, and it would soak up stem cells from the bone marrow. The way it is designed is that the top layer provides cues to the stem cells to form cartilage and the bottom layer provides cues for bone formation. That bottom layer is the same as the bone graft substitute, HydroxyColl, which we know has excellent capacity to regenerate bone. To achieve this, the scaffold is composed of a number of distinct but seamlessly integrated layers, designed to closely mimic physiological osteochondral tissue in terms of both composition and structure. Each of the individual layers has a composition tailored to mimic the native tissue with a gradient pore/fibre structure modelled on the superficial to deep zones of articular cartilage and underlying subchondral bone.
Q: OPN: What stage of development are you now at with the patch?
A: FO’B: Scientists always seem to talk about five-year plans, everything is five years away before it would go into patients, but we are actually now much closer and hope to see the start of clinical trials in 2014. Two years ago we set up a company called SurgaColl Technologies because you can’t really hope to move these types of technologies from the research lab directly to patients because of the big regulatory hurdles that exist. So we started a company and raised investment and the company has been focusing over the past year and a half to manufacture these products at a standard that means they can be implanted into humans. Our manufacturing process has now been certified as ‘safe’, so over the next couple of months we will be filing the submission for regulatory approval, so it can be used in patients. We do not envisage too many problems with the submission because of the way things have already gone. Our hope would be to have the bone graft technology HydroxyColl in humans this year, with the cartilage repair technology, ChondroColl, to follow in 2015.
Q: OPN: What testing has taken place of HydroxyColl and ChondroColl?
A: and has proved very successful. However, regarding the cartilage repair technology, because it is so difficult to regenerate cartilage, there tends to be some cynicism as to whether technologies that promote cartilage repair in small animals can actually regenerate cartilage in humans. So we have now assessed it in small animals in our own lab, horses in collaboration with colleagues in Utrecht, Holland, and major detailed analysis in goats at time points of up to one-year post implantation. The latter study has been carried out in collaboration with the veterinary school in University College Dublin. However, the UCD vet school also serves as a centre of excellence for clinical equine cases and we have started to work with them to treat horses suffering from some degenerative problems i.e. the vets came to us and asked if we would be willing to use our technologies – rather than merely testing them in animals, actually use them to treat animals. We have now had two cases, one of a horse with a massive bone cyst in its jaw and our technology HydroxyColl was used to treat that horse. That was very successful and the horse who might have been put down, a racehorse with a very fine bloodline, is now back racing. Similarly, ChondroColl has also recently been used to treat another horse with damaged knee joints and the last we heard it is also going well.
Q: OPN: What is the current situation with the two products?
A: FO’B: They are currently cell-free, growth factor-free and gene-free and we are hoping they will soon be in patients. Although they are complex technologies to develop, from a regulatory prospective they are relatively straightforward to get approval for because there is no real risk to the patient. Beyond these, our next-generation technologies are taking the likes of these materials and using them for drug delivery to enhance the regenerative capacity. So as well as bone and cartilage we are now focusing on cardiovascular tissues, nerve regeneration, corneal regeneration, we are even doing work in respiratory applications. Some of these type of applications are more complex and much trickier to get into patients because they would have to go through very stringent trials, as they often use drugs to enhance the regenerative capacity.
Q: OPN: What does your product mean for the future of orthopaedics?
A: FO’B: What we would hope is that the bone and cartilage repair technologies would help delay the requirement for knee replacements and hip replacements, especially, for example, in athletes and people who have been playing sport to a high level, who often come to orthopaedic surgeons and need to get isolated lesions to their joints repaired. These people often end up getting osteoarthritis, often very early in life, so we are trying to delay these people ending up getting hip or knee replacements. Our treatment might not prevent them completely but at least it means they might not get hip replacements in their late thirties or forties, but later on in life. In today’s world, more and more younger people need treatments much earlier in life. We are all living longer, so if you have a hip of knee replacement implanted when you are young, you are going to need that to be replaced again over time, so the longer you can delay these interventions the better.
For more information, visit the SurgaColl Technologies website, www.surgacoll.com
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David Warne
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E: david.warne@barkerbrooks.co.uk
