Piramal Life Sciences, India’s billion dollar (revenues) life sciences behemoth, had quietly invested in a novel cartilage repair technology—including funding numerous clinical studies and moving it through the regulatory processes around the world. Then, as it was ready to break into the U.S. market—Piramal sold the technology to Smith & Nephew.
The deal, whose terms were not disclosed, was announced by both Piramal and Smith & Nephew on January 12, 2016.
The technology, called BST-CarGel is a chitosan implant which has been shown to be an effective hyaline cartilage regeneration technology in a couple multicenter, randomized control clinical studies.
What Is BST-CarGel?
BST-CarGel is a first-line cartilage repair implant/fill which is designed to be used by the surgeon as part of a microfracture and other bone marrow stimulation procedures for treating most sizes of focal cartilage tears.
The implant, which is approved by regulatory authorities for clinical use in a number of countries around the world, including Australia, Canada and most of Europe, is a biopolymer, chitosan-based material which is mixed by the physician with a patient’s own blood and then implanted into the joint.
It can be delivered arthroscopically and, importantly, can be used to treat damaged cartilage in any synovial joint—whether knee, hip, ankle or shoulder.
Once implanted by the physician in the diseased joint, BST-CarGel acts as a scaffold, adhering to the cartilage surface to stabilize the blood clot creating conditions and, according to researchers who’ve tested it, will support cartilage regeneration and healing.
BST-CarGel’s Clinical Trials
There have been several clinical studies conducted by researchers which tests chitosan-beta glycerolphosphate-based implants (BST-CarGel) as an adjunct to microfracture. The most recent one was published in the journal Cartilage in 2015.
A list of all BST-CarGel’s studies is at the end of this article.
The study, which was sponsored by Piramal Life Sciences, enrolled 80 patients, aged 18 to 55 years, with grade III or IV focal lesions on the femoral condyles. Patients were randomized to receive BST-CarGel treatment with microfracture or microfracture alone and all patients followed the standardized 12-week rehabilitation.
Co-primary endpoints were repair tissue quantity and quality as evaluated using 3-dimensional MRI quantification of the degree of lesion filling (%) and T2 relaxation times. Secondary endpoints were clinical benefit measured with WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaires and safety.
The seven participating centers were:
- Dalhousie University, Halifax, Nova Scotia, Canada
- University of British Columbia, Vancouver, British Columbia, Canada
- CEU San Pablo University School of Medicine, Madrid, Spain
- University of Calgary Sports Medicine Centre, Calgary, Alberta, Canada
- Department of Orthopedics, CHA-Pavillon Enfant-Jesus, Quebec, Canada
- Hospital Charles LeMoyne, Greenfield Park, Quebec, Canada
- University of South Florida, Tampa, Florida, USA
As reported in the journal Cartilage, the researchers found, using a blinded MRI analysis, that patients treated with BST-CarGel had a significantly greater treatment effect for lesion filling (P = 0.017) over five years when compared to patients who’d been treated with microfracture alone.
The researchers also reported that they saw a significantly greater treatment effect for BST-CarGel for repair tissue T2 relaxation times (P = 0.026), which were closer to native cartilage as compared and contrasted to patients treated with microfracture alone.
Finally, patients treated with BST-CarGel and microfracture showed highly significant improvement at five years from pretreatment baseline for each WOMAC subscale (P < 0.0001), and there were no differences between the treatment groups. Safety was comparable for both groups.
After reviewing the study data, the researchers concluded that BST-CarGel was an effective mid-term cartilage repair treatment. At five years, patients treated with BST-CarGel had sustained and significantly superior repair tissue quantity and quality over microfracture alone. Clinical benefits following BST-CarGel and microfracture treatment were highly significant over baseline levels.
Chitosan
BST-CarGel is a chitosan-based product—which is quite different from other types of microfracture cartilage/bone fills.
Chitosan is a naturally occurring biologic whose active ingredients, chitin/chitosan, are found in the shells of crustaceans, such as lobsters, crabs, and shrimp. It is one of the most abundant biodegradable materials in the world.
Initially, chitosan was used in agriculture as an organic seed treatment and plant growth enhancer. Turns out chitosan increases photosynthesis, promotes and enhances plant growth, stimulates nutrient uptake, increases germination and sprouting, and boosts plant vigor. Using chitosan in agriculture reduced environmental stress due to drought and soil deficiencies, strengthened seed vitality, improved stand quality, increased yields, and reduced fruit decay of vegetables, fruits and citrus crops.
Chitosan applications for plants and crops are regulated by the EPA, and the USDA’s National Organic Program.
Now chitosan is building a market in trauma and orthopedics.
The first medical applications were to rapidly clot blood and the FDA approved it for bandages and other hemostatic agents. The U.S. Marine Corps tested chitosan and found that it quickly stopped bleeding resulting in 100% survival of otherwise lethal arterial wounds.
Chitosan hemostatics work better than gauze dressings and increase patient survival. Both the U.S. and UK used chitosan bandages on the battlefields of Iraq and Afghanistan.
Chitosan is hypoallergenic and naturally antibacterial. It also reduces pain by blocking nerve endings.
One last scientific point: as a hemostatic agent chitosan works by interacting between the cell membrane of erythrocytes (negative charge) and the protonated chitosan (positive charge) and thereby attracts platelets to speed up thrombus formation.
When chitosan breaks down in the body it becomes a glucosamine.
All of these capabilities open up many potential medical uses for chitosan. Aside from orthopedics, several companies have introduced chitosan products for burn treatment. Burns, like other wounds, are difficult to heal because they are associated with membrane destabilization, energy depletion, and hypoxia, all of which can cause tissue necrosis if not treated properly or quickly enough. Chitosan-gelation bandages using nano-fibrin have been shown to be more durable in clinical studies of burn treatments than ointments, while still allowing gas exchange at the cell surface.
How Smith & Nephew Will Roll Out BST-CarGel
Clearly, Smith & Nephew has an exciting and differentiated cartilage repair product on their hands.
The company will be marketing BST-CarGel as an adjunct to microfracture surgery where it acts as a scaffold and stabilizes the blood clot in the cartilage lesion. In clinical studies, BST-CarGel showed that it can impede blood clot retraction while still allowing normal clotting to occur. Finally it stays where it’s put by adhering to the cartilage lesion surface.
In animal studies, researchers found that BST-CarGel increased inflammatory and bone marrow derived stromal cell recruitment, increased vascularization of the provisional repair tissue and increased intra-membraneous bone formation and subchondral bone remodeling.
“BST-CarGel augments our existing joint repair portfolio with a new option that is differentiated with strong clinical evidence and targets an area of significant patient need and surgeon demand, ” said Scott Schaffner, vice president, Sports Medicine for Smith & Nephew. “We are committed to seeking and investing in next-generation technologies to widen access across our global customer base.”
Recent clinical studies of BST CarGel.
If you have any questions for Smith & Nephew about BST, email them to Vivek Munshi (vivek.munshi@smith-nephew.com).
2015
Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Méthot S, Vehik K, Restrepo A. “BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial”. Cartilage, 6(2): 62-72.
Tey M, Mas J, Pelfort X, Monllau JC. “Arthroscopic Treatment of Hip Chondral Defects With Bone Marrow Stimulation and BST-CarGel”. Arthroscopy Techniques – 4(1): e29-e33, 2015.
2014
Frappier J, Stanish W, Brittberg M, Steinwachs M, Crowe L, Castelo D, Restrepo A. “Economic evaluation of BST-CarGel® as an adjunct to microfracture vs microfracture alone in knee cartilage surgery”. Journal of Medical Economics 17(4) 266-278, 2014.
Restrepo A, Méthot S, Stanish WD, Shive MS. “BST-CarGel® Cartilage Repair Treatment. In Techniques in Cartilage Repair Surgery”. Ed Anan Shetty, Seok-Jung Kim, Norimasa Nakamura, and Mats Brittberg. Springer-ESSKA. 2014. ISBN 978-3-642-41920-1.
Shive MS, Restrepo A, Totterman S, Tamez-Peña J. Schreyer E, Steinwachs M. “Quantitative 3D MRI reveals limited intra-lesional bony overgrowth at 1 year after microfracture-based cartilage repair”. Osteoarthritis and Cartilage 22(6):800-804, 2014.
Steinwachs M, Waibl B, Mumme M. “Arthroscopic Treatment of Cartilage Lesions With Microfracture and BST-CarGel”. Arthroscopy Techniques – 3(3): e399-e402, 2014.
2013
Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, Shive MS. “Novel scaffold-based BST-CarGel® treatment results in superior cartilage repair compared to microfracture in a randomized controlled trial”. The Journal of Bone and Joint Surgery 95(18): 1640-1650, 2013.
2012
Méthot S, Stanish WD, McCormack R, Forriol Campos F, Mohtadi N, Pelet S, Desnoyers J, Changoor A, Tran-Khanh N, Roberts S, Shive MS, Restrepo A. “Polarized light microscopy and ICRS histological assessments as validated methodologies for the analysis of tissue quality in cartilage repair randomized controlled trials”. 10th World Congress of the International Cartilage Repair Society, Montreal, May 2012. Podium Presentation 25.3.3.
Shive MS, Stanish WD, McCormack R, Forriol Campos F, Mohtadi N, Pelet S, Desnoyers J, Tamez-Pena J, Totterman SM, Changoor A, Yaroshinsky A, Trattnig S, Restrepo A. “Standardized quantitative 3D MRI can detect superior cartilage repair in clinical trials and is correlated with collagen architecture in biopsies assessed by polarized light microscopy”. 10th World Congress of the International Cartilage Repair Society, Montreal, May 2012. Podium Presentation 11.4.4.
Stanish WD, McCormack R, Forriol Campos F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, Shive MS. “Novel scaffold-based BST-CarGel® treatment results in superior cartilage repair in a randomized controlled trial compared to microfracture”. 10th World Congress of the International Cartilage Repair Society, Montreal, May 2012. Podium Presentation 11.3.1.
2011
Changoor A, Tran-Khanh N, Méthot S, Garon M, Hurtig MB, Shive MS, Bushmann MD. “A polarized light microscopy method for accurate and reliable grading of collagen organization in cartilage repair”. Osteoarthritis and Cartilage 19(1):126-135, 2011a.
