J Knee Surg 2018; 31(07): 686-697
DOI: 10.1055/s-0037-1606575
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Comparison of Platelet-Rich Plasma, Stromal Vascular Fraction (SVF), or SVF with an Injectable PLGA Nanofiber Scaffold for the Treatment of Osteochondral Injury in Dogs

Samuel P. Franklin
1   Department of Small Animal Medicine and Surgery, University of Georgia, Athens, Georgia
2   Regenerative Bioscience Center, University of Georgia, Athens, Georgia
Aaron M. Stoker
3   Department of Orthopaedic Surgery/Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
Chantelle C. Bozynski
4   Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri
Keiichi Kuroki
4   Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri
Kevin M. Clarke
1   Department of Small Animal Medicine and Surgery, University of Georgia, Athens, Georgia
Jed K. Johnson
5   Nanofiber Solutions, Columbus, Ohio
James L. Cook
3   Department of Orthopaedic Surgery/Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
› Author Affiliations
Further Information

Publication History

31 May 2017

04 August 2017

Publication Date:
15 September 2017 (online)


Stromal vascular fraction (SVF) contains a small number of mesenchymal stem cells and has been used as a treatment for osteoarthritis and cartilage injury. Due to limited evidence of successful cartilage regeneration with injected stem cell therapies, there is interest in combining cellular therapies with injectable scaffolding materials to increase intra-articular residence times of stem cells and improve tissue regeneration. However, the safety of intra-articular injection of SVF combined with injectable scaffolds is unestablished. Also, it is unclear if SVF therapy is superior to more easily prepared biologics, such as platelet-rich plasma (PRP). The purpose of this study was to assess the safety of SVF when combined with an injectable poly(L-lactide-co-glycolide) nanofiber scaffold and to provide a comparison of SVF therapy to PRP. A total of 12 Beagles had osteochondral defects created in both medial femoral condyles and 4 dogs each were allocated to treatment groups of SVF (n = 4), SVF plus PLGA scaffolding (n = 4), or leukoreduced PRP (n = 4). One knee in each dog received treatment, and the contralateral knee was sham treated with saline. Dogs were assessed over a 6-month period, and outcome measures included functional, radiographic, biochemical, and histological assessments. PRP treatment resulted in improvements in lameness scores and objective kinetic assessments of function. There were no statistically significant improvements in function, cartilage biochemical composition, or histology for SVF-treated knees. The combination of SVF and the injectable PLGA scaffold had worse outcomes than other groups including sham treatment based upon functional, biochemical, and histological assessments, raising concerns over the safety of this scaffold for intra-articular injection.

  • References

  • 1 Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair. Tissue Eng Part B Rev 2010; 16 (01) 105-115
  • 2 Gregory MH, Capito N, Kuroki K, Stoker AM, Cook JL, Sherman SL. A review of translational animal models for knee osteoarthritis. Arthritis (Egypt) 2012; 2012 (12) 764621
  • 3 McCoy AM. Animal Models of Osteoarthritis: Comparisons and Key Considerations. Vet Pathol 2015; 52 (05) 803-818
  • 4 Allen MJ. Advances in total joint replacement in small animals. J Small Anim Pract 2012; 53 (09) 495-506
  • 5 Civinini R, Carulli C, Matassi F, Lepri AC, Sirleo L, Innocenti M. The survival of total knee arthroplasty: current data from registries on tribology: review article. HSS J 2017; 13 (01) 28-31
  • 6 Loveless MS, Fry AL. Pharmacologic therapies in musculoskeletal conditions. Med Clin North Am 2016; 100 (04) 869-890
  • 7 Rychel JK. Diagnosis and treatment of osteoarthritis. Top Companion Anim Med 2010; 25 (01) 20-25
  • 8 Akpancar S, Tatar O, Turgut H, Akyildiz F, Ekinci S. The current perspectives of stem cell therapy in orthopedic surgery. Arch Trauma Res 2016; 5 (04) e37976
  • 9 Marx C, Silveira MD, Beyer Nardi N. Adipose-derived stem cells in veterinary medicine: characterization and therapeutic applications. Stem Cells Dev 2015; 24 (07) 803-813
  • 10 Upchurch DA, Renberg WC, Roush JK, Milliken GA, Weiss ML. Effects of administration of adipose-derived stromal vascular fraction and platelet-rich plasma to dogs with osteoarthritis of the hip joints. Am J Vet Res 2016; 77 (09) 940-951
  • 11 Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M. , et al. Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy 2006; 8 (02) 166-177
  • 12 Sullivan MO, Gordon-Evans WJ, Fredericks LP, Kiefer K, Conzemius MG, Griffon DJ. Comparison of mesenchymal stem cell surface markers from bone marrow aspirates and adipose stromal vascular fraction sites. Front Vet Sci 2016; 2: 82
  • 13 Fortier LA, Travis AJ. Stem cells in veterinary medicine. Stem Cell Res Ther 2011; 2 (01) 9
  • 14 Taylor-Weiner H, Graff Zivin J. Medicine's wild west–unlicensed stem-cell clinics in the United States. N Engl J Med 2015; 373 (11) 985-987
  • 15 U.S. Department of Health and Human Services; Food and Drug Administration; Center for Biologics Evaluation and Research (CBER); Center for Devices and Radiological Health (CDRH); Office of Combination Products in the Office of the Commissioner (OCP). Human cells, tissues, and cellular and tissue-based products (HCT/Ps) from adipose tissue: regulatory considerations; draft guidance for industry. Available at: https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/tissue/ucm427811.pdf . Accessed August 30, 2017
  • 16 Fodor PB, Paulseth SG. Adipose derived stromal cell (ADSC) injections for pain management of osteoarthritis in the human knee joint. Aesthet Surg J 2016; 36 (02) 229-236
  • 17 Gibbs N, Diamond R, Sekyere EO, Thomas WD. Management of knee osteoarthritis by combined stromal vascular fraction cell therapy, platelet-rich plasma, and musculoskeletal exercises: a case series. J Pain Res 2015; 8: 799-806
  • 18 Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2015; 23 (05) 1308-1316
  • 19 Pak J, Lee JH, Park KS, Jeong BC, Lee SH. Regeneration of cartilage in human knee osteoarthritis with autologous adipose tissue-derived stem cells and autologous extracellular matrix. Biores Open Access 2016; 5 (01) 192-200
  • 20 Pak J, Lee JH, Park KS, Park M, Kang LW, Lee SH. Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications. J Biomed Sci 2017; 24 (01) 9
  • 21 Vadalà G, Papalia R, La Verde L, Russo F, Denaro V, Rosa MA. Bone marrow concentrated cells and stromal vascular fraction cells injections for osteoarthritis treatment: a systematic review. J Biol Regul Homeost Agents 2016; 30 (4, Suppl 1): 69-76
  • 22 Black LL, Gaynor J, Adams C. , et al. Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther 2008; 9 (03) 192-200
  • 23 Black LL, Gaynor J, Gahring D. , et al. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 2007; 8 (04) 272-284
  • 24 Pak J, Lee JH, Kartolo WA, Lee SH. Cartilage regeneration in human with adipose tissue-derived stem cells: current status in clinical implications. BioMed Res Int 2016; 2016 (16) 4702674
  • 25 Kiefer K, Lin K, Fitzpatrick N. , et al. Does adipose-derived stromal cell adjuvant therapy for fragmented medial coronoid process in dogs influence outcome? a pilot project. Veterinary Evid Online 2016; 1 (04) 1-17
  • 26 Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res 2009; 27 (12) 1675-1680
  • 27 Morille M, Toupet K, Montero-Menei CN, Jorgensen C, Noël D. PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis. Biomaterials 2016; 88: 60-69
  • 28 Morille M, Van-Thanh T, Garric X. , et al. New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells. J Control Release 2013; 170 (01) 99-110
  • 29 Solouk A, Mirzadeh H, Amanpour S. Injectable scaffold as minimally invasive technique for cartilage tissue engineering: in vitro and in vivo preliminary study. Prog Biomater 2014; 3: 143-151
  • 30 Beitzel K, Allen D, Apostolakos J. , et al. US definitions, current use, and FDA stance on use of platelet-rich plasma in sports medicine. J Knee Surg 2015; 28 (01) 29-34
  • 31 Franklin SP, Garner BC, Cook JL. Characteristics of canine platelet-rich plasma prepared with five commercially available systems. Am J Vet Res 2015; 76 (09) 822-827
  • 32 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 (01) 32-42
  • 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 (05) 658-665
  • 34 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 (04) 520-529
  • 35 Light VA, Steiss JE, Montgomery RD, Rumph PF, Wright JC. Temporal-spatial gait analysis by use of a portable walkway system in healthy Labrador Retrievers at a walk. Am J Vet Res 2010; 71 (09) 997-1002
  • 36 Roy RG, Wallace LJ, Johnston GR, Wickstrom SL. A retrospective evaluation of stifle osteoarthritis in dogs with bilateral medial patellar luxation and unilateral surgical repair. Vet Surg 1992; 21 (06) 475-479
  • 37 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 (05) 404-410
  • 38 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 3): S66-S79
  • 39 Farndale RW, Sayers CA, Barrett AJ. A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res 1982; 9 (04) 247-248
  • 40 Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 1996; 29 (03) 225-229
  • 41 Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther 2014; 16 (01) 204
  • 42 Fahie MA, Ortolano GA, Guercio V. , et al. A randomized controlled trial of the efficacy of autologous platelet therapy for the treatment of osteoarthritis in dogs. J Am Vet Med Assoc 2013; 243 (09) 1291-1297
  • 43 Franklin SP, Cook JL. Prospective trial of autologous conditioned plasma versus hyaluronan plus corticosteroid for elbow osteoarthritis in dogs. Can Vet J 2013; 54 (09) 881-884
  • 44 Cook JL, Smith PA, Bozynski CC. , et al. Multiple injections of leukoreduced platelet rich plasma reduce pain and functional impairment in a canine model of ACL and meniscal deficiency. J Orthop Res 2016; 34 (04) 607-615
  • 45 Yun S, Ku SK, Kwon YS. Adipose-derived mesenchymal stem cells and platelet-rich plasma synergistically ameliorate the surgical-induced osteoarthritis in Beagle dogs. J Orthop Surg 2016; 11: 9