New research from the Tissue Engineering Research Group (TERG) in the Royal College of Surgeons in Ireland (RCSI) has found that a novel biomaterial that can repair damaged knee cartilage has led to an injured thoroughbred filly, Beyoncé, returning to competitive show jumping following implantation of this biomaterial. Articular cartilage is found covering the end of bones within a synovial joint, where it serves as a cushion and shock absorber in the joint. When damaged as a result of disease or injury, cartilage has a poor ability to regenerate itself and tends to get worse over time and may progress through the cartilage to the underlying subchondral bone, termed an ‘osteochondral’ defect. While various treatment strategies have been developed, none result in long-term success and many patients go on to eventually require joint replacement. The treatment of cartilage defects thus poses a significant challenge for orthopaedic surgeons. The field of tissue engineering (TE) offers a potential solution to the problem. TE involves combining cells, biomaterials and suitable biochemical and physicochemical factors to repair or replace biological tissues. A team of researchers from the RCSI Tissue Engineering Research Group (led by Prof Fergal O’Brien, head of the RCSI Department of Anatomy and deputy director of AMBER) have developed a novel 3D biomaterial scaffold for osteochondral defect repair that acts as a template for the regeneration of new tissue. The osteochondral substitute scaffold is a multi-layer biodegradable implant designed to mimic the structure and composition of the natural osteochondral tissue. It consists of a bone phase, calcified cartilage phase and cartilage phase and is composed of collagen, hydroxyapatite and hyaluronic acid, materials native to articular joints. The structure and composition of the osteochondral substitute scaffold is specifically optimised to facilitate and promote osteochondral tissue healing. It is designed to have a highly porous (>95%) structure that encourages the infiltration of the body’s own cells and stimulates host stem-cells to regenerate both bone and cartilage, using the composition and architecture of the biomaterial to actively direct tissue formation. The scaffold thus presents an off-the-shelf solution for osteochondral repair.

Regenerative potential of osteochondral substitute scaffold

[caption id="attachment_30744" align="aligncenter" width="300"]Surgacoll CLICK TO ENLARGE: How the cartilage-repair technology works[/caption] The most recent study, the latest in a series of publications led by Dr Tanya Levingstone, research fellow and honorary lecturer in RCSI, investigating the regenerative potential of the osteochondral substitute scaffold has just been published in the Journal of Tissue Engineering and Regenerative Medicine, one of the leading journals in the field. This study relates to a recent case in University College Dublin’s (UCD) Veterinary Hospital and provided the first clinical use of this scaffold. The patient was a 16-month-old thoroughbred filly, ‘Beyoncé’, who had large areas of damage in both left and right stifle (knee) joints as a result of a disease known as osteochondritis dissecans (OCD), a developmental joint disorder in which cracks form in the articular cartilage and the underlying subchondral bone. The disease affects 10 per cent to 30 per cent of the equine population, depending on breed, and as such is a major concern in the horse industry. It is also common in humans, with prevalence estimated at 15 to 21 per 100,000. Surgical debridement of the defect site is the primary surgical strategy to facilitate healing in horses; however, prognosis is inversely proportionate to the defect size. For very large lesions, such as in Beyoncé’s case, the outcome is often poor and may lead to euthanasia of the animal in severe cases. David Stack and Florent David of UCD’s Veterinary Hospital carried out the surgical procedure. Unstable osteochondral fragments were removed and the osteochondral substitute scaffolds were then implanted providing a template for new cartilage and bone to be formed. Arthroscopic examination at five months post-implantation revealed smooth cartilaginous repair tissue covering the defect. At 22-month follow up, examination using x-ray and ultrasound showed the defects to be filled with bone with an overlying cartilaginous layer. The joint surface was seen to be smooth with no evidence of osteoarthritis and the horse had no signs of lameness and was exercising at her intended level. Beyoncé has since returned to training and will compete as a show jumper in the coming months. The successful repair achieved here using the osteochondral substitute scaffold in an equine patient with large bilateral lesions shows the potential for clinical translation in the treatment of human patients presenting with osteochondral defects.

Surgacoll and pre-clinical studies

Additional assessment of the regenerative potential of the osteochondral substitute scaffold in other pre-clinical cases has also shown promising results. The first, a short-term pilot study in a rabbit knee-joint model, was recently published in Acta Biomaterialia, the number-two journal in the biomaterials field, and demonstrated proof of concept compared to an untreated defect at 12 weeks post implantation. The second was a long term pre-clinical study, also carried out in conjunction with UCD’s School of Veterinary Medicine. This study demonstrated the ability of the scaffold to heal both partial load-bearing and full load-bearing defects in a goat knee joint at 12 months post implantation. In addition, the ability the osteochondral substitute scaffold to bring about improved healing compared to a commercial comparator scaffold was shown, and the benefit of employing natural biomaterials compared to synthetic biomaterials for cartilage repair applications was demonstrated. The study was recently published in Biomaterials, the leading specialist journal in the field. “We’re delighted with the outcomes from both pre-clinical studies and particularly with the results from the Beyoncé case,” said O’Brien. “Our hope for the future is this technology will benefit human patients and through our spinout company, SurgaColl Technologies, this is very close to becoming a reality with first human cases anticipated in the coming months.” The research related to the development and assessment of the technology received funding from Enterprise Ireland, Science Foundation Ireland and the Health Research Board. SurgaColl Technologies is currently bringing the technology to market, under the trade name ChondroColl. SurgaColl supplies novel tissue-regeneration products for the surgical treatment of disease of the bone, cartilage and other human tissue, based on technologies developed by the TERG. This is the second product from RCSI in SurgaColl’s pipeline. Its first product, a bone regeneration scaffold called HydroxyColl, offers bone-healing equivalent to a patient’s own bone when used as a medical implant in the treatment of bone defects. It has recently been CE approved and is now available in the marketplace. Regulatory approval is anticipated by the end of 2016 and first in-human use of the ChondroColl scaffold is planned in the coming months. About TERG The RCSI Tissue Engineering Research Group (TERG) is a large multidisciplinary research group focused on the development of cell and advanced biomaterial-based strategies for the repair and regeneration of bone, cartilage, cardiovascular, ocular, respiratory and neural tissues. It works closely with the Centre for Bioengineering in Trinity College Dublin and is also part of the €58 million Science Foundation Ireland funded research centre, AMBER (Advanced Materials and BioEngineering Research) which is focused on developing advanced next generation materials and medical devices in partnership with industry. Journal references: 1) Stack JD, Levingstone TJ, Lalor W, Sanders R, Kearney C, O'Brien FJ, David F. (2016) 'Repair of large osteochondritis dissecans lesions using a novel multilayered tissue engineered construct in an equine athlete.' Journal of Tissue Engineering and Regenerative Medicine. Online : 20 May 2016, doi:10.1002/term.2173 2) Levingstone TJ, Ramesh A, Brady RT, Brama PAJ, Kearney C, Gleeson, JP, O’Brien, FJ. (2016) 'Cell-free multi-layered collagen-based scaffolds demonstrate layer specific regeneration of functional osteochondral tissue in caprine joints.' Biomaterials 87, 69-81. doi:10.1016/j.biomaterials.2016.02.006 3) Levingstone TJ, Thompson, E, Matsiko, A, Schepens, A, Gleeson, JP, O’Brien, FJ. (2016) 'Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits.' Acta Biomaterialia, 32, 149-160. doi:10.1016/j.actbio.2015.12.034 4) Levingstone, TJ, Matsiko, A, Dickson, G, O'Brien, FJ and Gleeson JP. (2014) 'A biomimetic multi-layered collagen-based scaffold for osteochondral repair.' Acta Biomaterialia, 10 (5):1996-2004. doi:10.1016/j.actbio.2014.01.005