By Margaret Evans

Beyoncé, a bay Thoroughbred filly owned by Patricia and Will Lalor, whose barn is based in Clonmel, Ireland, was destined for a show jumping career. But at 16 months of age she was diagnosed with a condition known as osteochondritis dissecans (OCD), which had developed in her left and right knees. It is a common orthopaedic developmental disease in many species including humans, and results in separation of the articular cartilage from the underlying bone in the joints. Depending on the breed, it can affect 10 to 30 percent of the equine population. 

But then Beyoncé became the recipient of an exciting new procedure which could prove to be a game-changer, not only for equines, but for humans with similar orthopaedic issues.

“Signs of OCD can be seen as early as five months of age, but it can be detected at any age,” says Dr. Tanya Levingstone, honorary research lecturer at the Royal College of Surgeons in Ireland (RCSI). “It commonly affects both knee joints in horses. The horse in this case study was affected particularly badly and had very large OCD lesions in both knee joints. Thus, in this case, the prognosis from conventional treatment methods was poor.”

Dr. Tanya Levingstone, Research Fellow and Honorary Research Lecturer in RCSI, with William Lalor, one of Beyoncé’s owners, and Beyoncé. Photo courtesy of Tanya Levingstone

OCD usually starts before a foal is a yearling and, without intervention, can lead to several bone and joint problems later in life. Normally, the soft cartilage cells of a young horse convert naturally to solid bone and the process is known as endochondral ossification. But with OCD horses, this normal progression doesn’t happen as it should, and small areas of damaged cartilage occur within the joint causing the cartilage and the bone beneath it to become irregular in thickness and weaker than in normal, healthy joints.

The interesting thing about OCD is that, in many cases, it can be a self-healing disease. For foals, some defects may heal naturally and the bone continues with normal growth. But once they reach yearling age that progression from cartilage to bone slows and stops, and there is less likelihood of natural healing and a greater possibility of OCD developing. It can lead to the development of bone flaps and fragments of cartilage that might remain partially attached or break away and float around the joint, causing irritation and inflammation leading to swelling. Over time, these abnormal growths may lead to arthritis. The syndrome is called osteochondritis and the loose flaps and fragments are referred to as dissecans.

The most common sign of a horse with OCD is an enlarged joint, swollen with extra fluid due to inflammation. The symptoms may present as lameness to varying degrees, which can be more pronounced on some days than others. They may also include awkwardness in moving, unusual stiffness, poor impulsion, or difficulties getting up and down.

The condition may be caused by a number of factors including rapid growth in young horses, a large body size, dietary imbalance, hormonal imbalance, genetics, trauma, and/or exercise. It is found almost exclusively in domestic horses and suggestions are that the genetics of breeding larger, faster-growing horses have contributed to the condition. Breeds such as Warmbloods, Thoroughbreds, and Standardbreds can be prone to OCD. But the genomics are such that it is not easy to eliminate the condition by selective breeding since the disease involves multiple genes and any attempt might lead to other unintended consequences.

And there are natural, preventative measures. Foals, especially newborns in their first few months, benefit from having free access to pastures and fields where they can run and play, encouraging normal, healthy bone growth rather than limited movement in the confines of a stall environment. Horses were built to move, and it is that constant movement that maintains all their normal, healthy functions, especially during the critical growing period.

When they do develop, joint lesions can be problematic to treat, especially in more severe cases like those in Beyoncé’s situation, which involved both knees.

Current treatment is to remove the bone chips through an arthroscopy procedure, or keyhole surgery, which Beyoncé received in order to debride the site down to healthy tissue. Then she received a 3D porous collagen-based scaffold designed to replicate the tissue layers in the joint that included cartilage, calcified cartilage, and bone.

“Surgery was carried out by veterinary surgeons David Stack and Florent David in University College Dublin,” says Levingstone. “During the surgical procedure, the OCD lesion sites were debrided back to healthy tissue and the scaffold material was cut to size and implanted into the site. The porous structure of the scaffold enables cells within the defect and joint to infiltrate into the scaffold where the specifically tailored scaffold composition and structure directs these cells to form bone, calcified cartilage, and cartilage within the specified regions, thus healing the damaged joint.”

The biomaterials in the scaffold are composed of layers of collagen, hydroxyapatite and hyaluronic acid, materials found in joints. Basically, the scaffold formed a template for new cartilage and bone to form and encourages the body’s own cells to regenerate and repair the damaged areas.

The 3D scaffold technology was developed by Levingstone, Prof. Fergal O’Brien who headed the project, and Dr. John Gleeson in the Tissue Engineering Research Group (TERG) in RCSI. In addition, scientists with the Advanced Materials and BioEngineering Research (AMBER) Centre also contributed. AMBER brings together Ireland’s materials science researchers working across the disciplines of physics, chemistry, bioengineering, and medicine, and they work with an international network of collaborators and companies.

The scaffold was fabricated using a patented “iterative freeze-drying” process and consisted of three seamlessly integrated layers that replicated the cartilage, calcified cartilage, and bone tissue within the joint.

Each individual layer has a composition just like the natural tissue with the pore and fibre structure modelled along the lines of the zones within the cartilage and bone. In the bigger picture, and especially from a human perspective, the procedure offers options for early intervention by orthopaedic surgeons in the treatment of damaged cartilage and may offer options to delay the need for full joint replacement.

Osteochondritis dessicans (OCD) is a relatively common orthopaedic developmental disease that affects the bone and cartilage in the joints of horses. It can lead to fragments of bone and cartilage becoming loose within the joint, causing irritation and inflammation. X-ray photo courtesy of Kleider Veterinary Services. OCDs photo courtesy of April D. Ray.

Recovery following OCD surgeries typically requires a period of stall rest followed by gentle, progressive exercise. It may be several months before a horse can return to training. Bandaging, and medication including anti-inflammatory drugs, will also likely be required. Suture removal and follow-up examinations will monitor the progression of recovery and each horse will have a program of care according to the extent of the surgery and veterinary guidance. The encouraging news is that the prognosis for future athletic performance is often good to excellent after OCD surgery, depending on the surgical location. In general, though, without surgery, future soundness will always be in doubt.

Beyoncé recovered well following her surgery. Exploratory arthroscopy five months after surgery showed smooth cartilage tissue covering the defect. The filly returned to training and at the 22-month follow-up she continued to be sound with no sign of lameness and was exercising at the desired level. The ridges were smooth and the defects were filled with bone and covered with cartilage. 

Levingstone says that it has now been five years since the surgery was done and the mare remains healthy, sound, and continues her training program at the intended level. The young mare has returned to competitive show jumping, much to the relief of her owners.

Levingstone says that the technology used on Beyoncé offers enormous potential. “The technology has been licensed to SurgaColl Technologies Ltd., a spin-out company from the Royal College of Surgeons in Ireland focused on translating technologies from Prof. O’Brien’s lab to the clinic. [It] is being commercialized under the tradename ChondroColl. SurgaColl is currently planning a number of human clinical trials within the UK and Ireland to evaluate the potential of this technology, not only within the knee joint but also in other cartilaginous joints such as the ankle and shoulder. They are also investigating further use within the veterinary market and continue to use the material in veterinary case studies, helping to prevent unnecessary deaths of animals that suffer with chronic disease conditions within their joints.”

SurgaColl Technologies is exploring commercial opportunities of this scaffold for equine applications and they regularly receive requests from equine surgeons around the world including Kentucky, United States, and South Africa. The global interest underscores the significant veterinary market for new technologies that are proving to have such a positive effect on the welfare of horses.

“SurgaColl has recently helped treat another horse with their other approved product, an innovative orthobiologic bone graft substitute named HydroxyColl,” says Levingstone. “[It has] similar composition to the bone healing layers of ChondroColl.”

HydroxyColl combines bone’s two main ingredients, collagen and hydroxyapatite, in a bioactive scaffold to repair bone tissue defects. Collagen is a natural biopolymer (a large molecule in a living organism). Hydroxyapatite is the natural ceramic mineral in bone tissue giving bones and teeth their rigidity. HydroxyColl directs bone regeneration and is completely replaced by newly formed, healthy bone tissue.

Levingstone says that the procedure to treat a horse with HydroxyColl was done in the UK with the continued help of David Stack, the veterinary surgeon who carried out the original treatment with Beyoncé. 

“The products are currently applicable for veterinary use and the company has begun to explore potential sales and distribution opportunities,” she says. “The unanimously positive endorsements from 100 percent of the veterinary surgeons that have helped develop and/or worked with the final approved products has helped SurgaColl to attract potential partners and large veterinary practice groups that have a need for a cost-effective solution with market-beating performance in such large animals and defects.”

She says that three human patients have been treated in a clinical study which investigated the human application of the scaffold. The study was led by RCSI, Prof. Cathal Moran and Prof. John O’Byrne, two consultant orthopaedic surgeons who have been pioneering the technology with very positive results.

“SurgaColl has also started to engage a number of EU clinical sites and has received provisional ethical support for conducting a multi-site randomized clinical trial to conclusively demonstrate the performance of the technology in a large cohort of human patients.”

Levingstone says that Dr. John Gleeson, SurgaColl CTO, cofounder and coinventor of the technologies, is very excited about the potential to translate the performance seen in animals into the human clinical setting. 

“Dr. Gleeson has already seen SurgaColl’s first product, HydroxyColl, significantly improve patients’ outcomes firsthand,” she says, quoting his response: “’It is an amazing experience to be involved in the first stages of the invention of a novel medical implant device, and then being fortunate enough to ultimately be in theatre, with the operating surgeon and patient undergoing surgery, and to see your product being implanted and making a meaningful impact on patients’ lives. It is an amazing privilege as a scientist.’”

Moving forward, Levingstone says, the next generation of technologies from Prof. O’Brien’s lab is using materials like these but combining them with stem cells and gene therapy to target even more complex injuries that can lead to osteoarthritis.

It is clearly an exciting time to be in equine research and surgery. Horses today are able to benefit from many procedures that offer them so many options to live healthy, competitive lives. 

The study Repair of large osteochondritis dissecans lesions using a novel multilayered tissue engineered construct in an equine athlete was published in the Journal of Tissue Engineering and Regenerative Medicine.

Main photo: Osteochondritis dessicans usually starts before the foal is a year old and if untreated can cause bone and joint problems later in life. Photo: Shutterstock/Noor Ali Ahmed