01762: Use of Plasma-Derived Growth Factors to Heal Cruciate Rupture
Grant Status: Closed
Project Summary
Over the last year, we have completed patient recruitment and recheck examinations for this study. We enrolled 29 dogs in this prospective clinical trial, 27 of which completed the study. One dog was lost to follow up and one dog died before completion of the study due to unrelated disease. All dogs enrolled in the study had a cruciate rupture in one knee and evidence of early disease in the second knee. All dogs were treated with tibial plateau leveling osteotomy (TPLO) for cruciate rupture and were given a platelet-rich plasma regenerative medicine treatment for the cruciate ligaments in the second stable knee with early disease.
The tissue engineering treatment we used consisted of a collagen slurry prepared in the laboratory. The collagen was mixed with platelet-rich plasma collected from the patient at the time of surgical treatment. Platelets were concentrated using a centrifuge and injected into the knee joint around the cruciate ligaments. Platelets are a specialized type of blood cell that are rich in growth factors that have the potential to stimulate ligament healing and reduce joint inflammation. By mixing the platelets with collagen, the release of growth factors is slowed in order to enhance tissue healing as much as possible. We did not detect any complications associated with the regenerative medicine treatment in this group of dogs.
We used two high-resolution magnetic resonance imaging sequences to quantitatively assess the cruciate ligaments within the knee joint at the time of diagnosis and at 12-months after surgery. This has been accomplished in collaboration with medical physics faculty at the University of Wisconsin-Madison. The sequences we used provide excellent contrast between the tendon, ligament, fat, cartilage, and bone tissues that make up the knee joint. MRI image data will be subsequently examined to determine whether specific abnormalities can be identified that are predictive of a second cruciate rupture.
We found that for all dogs, treatment with the platelet-collagen gel for early disease of the cruciate ligaments in the contralateral stable stifle during TPLO treatment of the unstable stifle with complete cruciate rupture was safe and easy to perform. Before surgery, contralateral cranial cruciate ligament volume was estimated using three Tesla magnetic resonance imaging. Knee joint instability was quantified using weight-bearing radiographs, which were repeated at 10 weeks and 12 months after surgery. Contralateral cranial cruciate ligament damage was scored arthroscopically and then treated by filling the intercondylar notch with the platelet-collagen gel. Functional cruciate length during weight-bearing and severity of knee arthritis were determined radiographically preoperatively and at 10 weeks and 12 months after surgery. Cranial cruciate ligament damage was noted in all contralateral stifles during arthroscopic examination. One dog experienced a contralateral superficial wound infection that resolved with treatment.
We have compared development of subsequent contralateral cruciate rupture after regenerative medicine treatment with platelet-rich plasma to a large group of historic control dogs from our institution that were given standard of care treatment without any specific treatment for the incipient cruciate rupture in the contralateral stifle (Chuang et al. 2014).
Preliminary analysis evaluating development of a second cruciate rupture in the platelet- collagen gel treated knees indicates that treatment did not protect dogs from developing cruciate rupture over the year after treatment.
We recently completed the final 12-month recheck evaluation and are now working to analyze the complete data from this study. Preliminary analysis suggests that the platelet-rich plasma treatment is not disease-modifying.
Publication(s)
Fazio, C. G., Muir, P., Schaefer, S. L., & Waller, K. R. (2017). Accuracy of 3 Tesla magnetic resonance imaging using detection of fiber loss and a visual analog scale for diagnosing partial and complete cranial cruciate ligament ruptures in dogs. Veterinary Radiology & Ultrasound, 59(1), 64–78. https://doi.org/10.1111/vru.12567
Racette, M., Al saleh, H., Waller, K. R., Bleedorn, J. A., McCabe, R. P., Vanderby, R., … Muir, P. (2016). 3D FSE Cube and VIPR-aTR 3.0 Tesla magnetic resonance imaging predicts canine cranial cruciate ligament structural properties. The Veterinary Journal, 209, 150–155. https://doi.org/10.1016/j.tvjl.2015.10.055
Sample, S. J., Racette, M. A., Hans, E. C., Volstad, N. J., Holzman, G., Bleedorn, J. A., … Muir, P. (2017). Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture. PLOS ONE, 12(6), e0178086. https://doi.org/10.1371/journal.pone.0178086
Sample, S. J., Racette, M. A., Hans, E. C., Volstad, N. J., Schaefer, S. L., Bleedorn, J. A., … Muir, P. (2018). Use of a platelet-rich plasma-collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs. PLOS ONE, 13(6), e0197204. https://doi.org/10.1371/journal.pone.0197204
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