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J Knee Surg 2016; 29(07): 594-603
DOI: 10.1055/s-0035-1570115
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acute Management of Anterior Cruciate Ligament Injuries Using Novel Canine Models

Chantelle C. Bozynski
1   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
James P. Stannard
2   Department of Orthopaedic Surgery, University of Missouri Hospital, Columbia, Missouri
,
Pat Smith
3   Department of Orthopaedic Surgery, Columbia Orthopaedic Group, Columbia, Missouri
,
Bryan T. Hanypsiak
4   Department of Orthopaedic Surgery, Peconic Bay Medical Center, Riverhead, New York
,
Keiichi Kuroki
1   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
Aaron Stoker
1   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
Cristi Cook
1   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
James L. Cook
1   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
› Author Affiliations
Further Information

Publication History

14 August 2015

02 November 2015

Publication Date:
29 December 2015 (online)

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Abstract

The objective of this study was to compare treatment options for acute management of anterior cruciate ligament (ACL) injuries using preclinical models. Twenty-seven adult purpose-bred research hounds underwent knee surgery (sham control, exposed ACL, or partial-tear ACL) and were assessed over the following 8 weeks. Dogs were randomized into three treatment groups: standard of care (i.e., rest and nonsteroidal anti-inflammatory drugs [NSAIDs]), washout, or leukoreduced platelet-rich plasma (PRP) so that a total of nine dogs received each treatment. Data from the two ACL-injury groups were pooled for each treatment (n = 6 per treatment group) and analyzed for treatment effects. The washout and PRP groups experienced less lameness, pain, and effusion, and greater function and comfortable range of motion compared with the NSAID group, with the PRP group showing most benefits. PRP was associated with the lowest severity of ACL pathology based on arthroscopic assessment. Measurable levels of inflammatory and degradative biomarkers were present in synovial fluid with significant differences noted over time. Based on these findings, washout had positive clinical effects compared with the standard-of-care group especially within the first week of treatment, but became less beneficial over time. A single injection of leukoreduced PRP was associated with favorable clinical results. However, no treatment was significantly “protective” against progression toward osteoarthritis after ACL injury.

Keywords

platelet-rich plasma - autologous conditioned plasma - anterior cruciate ligament - biomarkers - canine model
 

  • References

  • 1 Seijas R, Ares O, Cuscó X, Alvarez P, Steinbacher G, Cugat R. Partial anterior cruciate ligament tears treated with intraligamentary plasma rich in growth factors. World J Orthod 2014; 5 (3) 373-378
    CrossrefPubMedGoogle Scholar
  • 2 Spindler KP, Wright RW. Clinical practice. Anterior cruciate ligament tear. N Engl J Med 2008; 359: 2135-2142
    CrossrefPubMedGoogle Scholar
  • 3 Beynnon BD, Johnson RJ, Abate JA, Fleming BC, Nichols CE. Treatment of anterior cruciate ligament injuries, part I. Am J Sports Med 2005; 33 (10) 1579-1602
    CrossrefPubMedGoogle Scholar
  • 4 Lai LP, Stitik TP, Foye PM, Georgy JS, Patibanda V, Chen B. Use of platelet-rich plasma in intra-articular knee injections for osteoarthritis: a systemic review. PM R 2015; 7 (6) 637-648
    CrossrefPubMedGoogle Scholar
  • 5 Zhang W, Moskowitz RW, Nuki G , et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage 2007; 15 (9) 981-1000
    CrossrefPubMedGoogle Scholar
  • 6 Zhang W, Moskowitz RW, Nuki G , et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008; 16 (2) 137-162
    CrossrefPubMedGoogle Scholar
  • 7 Zhang W, Nuki G, Moskowitz RW , et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010; 18 (4) 476-499
    CrossrefPubMedGoogle Scholar
  • 8 Garner BC, Stoker AM, Kuroki K, Evans R, Cook CR, Cook JL. Using animal models in osteoarthritis biomarker research. J Knee Surg 2011; 24 (4) 251-264
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7 (1) 33-42
    CrossrefPubMedGoogle Scholar
  • 10 Cook JL. Cranial cruciate ligament disease in dogs: biology versus biomechanics. Vet Surg 2010; 39 (3) 270-277
    CrossrefPubMedGoogle Scholar
  • 11 Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound?. Curr Opin Rheumatol 2008; 20 (5) 565-572
    CrossrefPubMedGoogle Scholar
  • 12 Kuroki K, Stoker AM, Cook JL. Effects of proinflammatory cytokines on canine articular chondrocytes in a three-dimensional culture. Am J Vet Res 2005; 66 (7) 1187-1196
    CrossrefPubMedGoogle Scholar
  • 13 Ray A, Kuroki K, Cook JL , et al. Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis. Arthritis Rheum 2003; 48 (1) 134-145
    CrossrefPubMedGoogle Scholar
  • 14 Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR. Osteoarthritis or osteoarthrosis: the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthritis Cartilage 2002; 10 (1) 1-4
    CrossrefPubMedGoogle Scholar
  • 15 Richardson DW, Dodge GR. Effects of interleukin-1beta and tumor necrosis factor-alpha on expression of matrix-related genes by cultured equine articular chondrocytes. Am J Vet Res 2000; 61 (6) 624-630
    CrossrefPubMedGoogle Scholar
  • 16 Goldring MB. The role of cytokines as inflammatory mediators in osteoarthritis: lessons from animal models. Connect Tissue Res 1999; 40 (1) 1-11
    CrossrefPubMedGoogle Scholar
  • 17 Cameron-Donaldson M, Holland C, Hungerford DS, Frondoza CG. Cartilage debris increases the expression of chondrodestructive tumor necrosis factor-alpha by articular chondrocytes. Arthroscopy 2004; 20 (10) 1040-1043
    CrossrefPubMedGoogle Scholar
  • 18 Felson DT. Arthroscopy as a treatment for knee osteoarthritis. Best Pract Res Clin Rheumatol 2010; 24 (1) 47-50
    CrossrefPubMedGoogle Scholar
  • 19 Rosenthal AK. Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol 2011; 23 (2) 170-173
    CrossrefPubMedGoogle Scholar
  • 20 Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA. Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy 2012; 28 (3) 429-439
    CrossrefPubMedGoogle Scholar
  • 21 Hutchinson ID, Rodeo SA, Perrone GS, Murray MM. Can platelet-rich plasma enhance anterior cruciate ligament and meniscal repair?. J Knee Surg 2015; 28 (1) 19-28
    PubMedGoogle Scholar
  • 22 Mascarenhas R, Saltzman BM, Fortier LA, Cole BJ. Role of platelet-rich plasma in articular cartilage injury and disease. J Knee Surg 2015; 28 (1) 3-10
    PubMedGoogle Scholar
  • 23 Tang YQ, Yeaman MR, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun 2002; 70 (12) 6524-6533
    CrossrefPubMedGoogle Scholar
  • 24 Filardo G, Kon E, Buda R , et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2011; 19 (4) 528-535
    CrossrefPubMedGoogle Scholar
  • 25 Filardo G, Kon E, DI Matteo B , et al. Leukocyte-poor PRP application for the treatment of knee osteoarthritis. Joints 2013; 1 (3) 112-120
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Kon E, Mandelbaum B, Buda R , et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 2011; 27 (11) 1490-1501
    CrossrefPubMedGoogle Scholar
  • 27 Cook JL, Hung CT, Kuroki K , et al. Animal models of cartilage repair. Bone Joint Res 2014; 3 (4) 89-94
    CrossrefPubMedGoogle Scholar
  • 28 Cook JL, Kuroki K, Visco D, Pelletier JP, Schulz L, Lafeber FP. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the dog. Osteoarthritis Cartilage 2010; 18 (Suppl. 03) S66-S79
    PubMedGoogle Scholar
  • 29 Bozynski CC, Kuroki K, Stannard JP , et al. Evaluation of partial transection versus synovial debridement of the ACL as novel canine models for management of ACL injuries. J Knee Surg 2015; 28 (5) 404-410
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Luther JK, Cook CR, Cook JL. Meniscal release in cruciate ligament intact stifles causes lameness and medial compartment cartilage pathology in dogs 12 weeks postoperatively. Vet Surg 2009; 38 (4) 520-529
    CrossrefPubMedGoogle Scholar
  • 31 Cook JL, Fox DB, Malaviya P , et al. Long-term outcome for large meniscal defects treated with small intestinal submucosa in a dog model. Am J Sports Med 2006; 34 (1) 32-42
    CrossrefPubMedGoogle Scholar
  • 32 Hudson JT, Slater MR, Taylor L, Scott HM, Kerwin SC. Assessing repeatability and validity of a visual analogue scale questionnaire for use in assessing pain and lameness in dogs. Am J Vet Res 2004; 65 (12) 1634-1643
    CrossrefPubMedGoogle Scholar
  • 33 Cook JL, Tomlinson JL, Kreeger JM, Cook CR. Induction of meniscal regeneration in dogs using a novel biomaterial. Am J Sports Med 1999; 27 (5) 658-665
    CrossrefPubMedGoogle Scholar
  • 34 Mahn MM, Cook JL, Cook CR, Balke MT. Arthroscopic verification of ultrasonographic diagnosis of meniscal pathology in dogs. Vet Surg 2005; 34 (4) 318-323
    CrossrefPubMedGoogle Scholar
  • 35 Hasegawa A, Nakahara H, Kinoshita M, Asahara H, Koziol J, Lotz MK. Cellular and extracellular matrix changes in anterior cruciate ligaments during human knee aging and osteoarthritis. Arthritis Res Ther 2013; 15 (1) R29
    CrossrefPubMedGoogle Scholar
  • 36 Mullaji AB, Marawar SV, Simha M, Jindal G. Cruciate ligaments in arthritic knees: a histologic study with radiologic correlation. J Arthroplasty 2008; 23 (4) 567-572
    CrossrefPubMedGoogle Scholar
  • 37 Monibi F, Roller BL, Stoker A, Garner B, Bal S, Cook JL. Identification of synovial fluid biomarkers for knee osteoarthritis and correlation with radiographic assessment. J Knee Surg 2015; (e-pub ahead of print). PMID:25927354
    PubMedGoogle Scholar
  • 38 Bashir J, Panero AJ, Sherman AL. The emerging use of platelet-rich plasma in musculoskeletal medicine. J Am Osteopath Assoc 2015; 115 (1) 24-31
    PubMedGoogle Scholar
  • 39 Campbell KA, Saltzman BM, Mascarenhas R , et al. Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy 2015; 31 (11) 2213-2221
    CrossrefPubMedGoogle Scholar
  • 40 Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. Am J Sports Med 2015; (e-pub ahead of print). PMID:25925602
    PubMedGoogle Scholar
  • 41 Multiple injections of leukoreduced platelet rich plasma reduce pain and functional impairment in a canine model of ACL and meniscal deficiency. J Orthop Res 2015; (epub ahead of print). PMID: 26403590
    PubMedGoogle Scholar