Skip to main content
SpringerLink
Log in

Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment

  • Emerging Trends in Biomaterials Research
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Osteoarthritis (OA) is a progressive, degenerative disease of articulating joints that not only affects the elderly, but also involves younger, more active individuals with prolonged participation in high physical-demand activities. Thus, effective therapies that are easy to adopt clinically are critical in limiting the societal burden associated with OA. This review is focused on intra-articular injectable regimens and provides a comprehensive look at existing in vivo models of OA that might be suitable for developing, testing, and finding a cure for OA by intra-articular injections. We first discuss the pathology, molecular mechanisms responsible for the initiation and progression of OA, and challenges associated with disease-specific targeting of OA. We proceed to discuss available animal models of OA and provide a detailed perspective on the use of mouse models in studies of experimental OA. We finally provide a closer look at intra-articular injectable treatments for OA, focusing on biomaterials-based nanoparticles, and provide a comprehensive overview of the various nanometer-size ranges studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Abramson, S. B. Osteoarthritis and nitric oxide. Osteoarthritis Cartilage 16(Suppl 2):S15–S20, 2008.

    Article  PubMed  Google Scholar 

  2. Arrich, J., et al. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ 172:1039–1043, 2005.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bajpayee, A. G., M. Scheu, A. J. Grodzinsky, and R. M. Porter. A rabbit model demonstrates the influence of cartilage thickness on intra-articular drug delivery and retention within cartilage. J. Orthop. Res. 33:660–667, 2015.

    Article  CAS  PubMed  Google Scholar 

  4. Bakker, A. C., et al. Prevention of murine collagen-induced arthritis in the knee and ipsilateral paw by local expression of human interleukin-1 receptor antagonist protein in the knee. Arthritis Rheum. 40:893–900, 1997.

    Article  CAS  PubMed  Google Scholar 

  5. Balazs, E. A., and J. L. Denlinger. Viscosupplementation—a new concept in the treatment of osteoarthritis. J. Rheumatol. 20:3–9, 1993.

    Google Scholar 

  6. Bannuru, R., N. Natov, U. Dasi, C. Schmid, and T. McAlindon. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis–meta-analysis. Osteoarthr. Cartil. 19:611–619, 2011.

    Article  CAS  PubMed  Google Scholar 

  7. Barve, R. A., et al. Transcriptional profiling and pathway analysis of monosodium iodoacetate-induced experimental osteoarthritis in rats: relevance to human disease. Osteoarthr. Cartil. 15:1190–1198, 2007.

    Article  CAS  PubMed  Google Scholar 

  8. Bellamy, N., et al. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Db. Syst. Rev. 2:CD005328, 2005.

    Google Scholar 

  9. Bishnoi, M., A. Jain, P. Hurkat, and S. K. Jain. Aceclofenac-loaded chondroitin sulfate conjugated SLNs for effective management of osteoarthritis. J. Drug Target. 22:805–812, 2014.

    Article  CAS  PubMed  Google Scholar 

  10. Bove, S. E., et al. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthr. Cartil. 11:821–830, 2003.

    Article  CAS  PubMed  Google Scholar 

  11. Boyce, B. F., and L. Xing. The RANKL/RANK/OPG pathway. Curr Osteoporos Rep 5:98–104, 2007.

    Article  PubMed  Google Scholar 

  12. Brown, T. D., R. C. Johnston, C. L. Saltzman, J. L. Marsh, and J. A. Buckwalter. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J. Orthop. Trauma 20:739–744, 2006.

    Article  PubMed  Google Scholar 

  13. Cashman, J. N. The mechanisms of action of NSAIDs in analgesia. Drugs 52(Suppl 5):13–23, 1996.

    Article  CAS  PubMed  Google Scholar 

  14. Chang, K. V., M. Y. Hsiao, W. S. Chen, T. G. Wang, and K. L. Chien. Effectiveness of intra-articular hyaluronic acid for ankle osteoarthritis treatment: a systematic review and meta-analysis. Arch. Phys. Med. Rehabil. 94:951–960, 2013.

    Article  PubMed  Google Scholar 

  15. Chen, Z., et al. Hyaluronic acid-coated bovine serum albumin nanoparticles loaded with brucine as selective nanovectors for intra-articular injection. Int J Nanomed. 8:3843–3853, 2013.

    Article  Google Scholar 

  16. Chen, Z., et al. Development of nanoparticles-in-microparticles system for improved local retention after intra-articular injection. Drug Deliv. 21:342–350, 2014.

    Article  CAS  PubMed  Google Scholar 

  17. Chevalier, X. Intraarticular treatments for osteoarthritis: new perspectives. Curr. Drug Targets 11:546–560, 2010.

    Article  PubMed  Google Scholar 

  18. Chevalier, X., et al. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. J. Rheumatol. 32:1317–1323, 2005.

    CAS  PubMed  Google Scholar 

  19. Christiansen, B. A., et al. Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis. Osteoarthr. Cartil. 20:773–782, 2012.

    Article  CAS  PubMed  Google Scholar 

  20. Coleman, P. J., D. Scott, J. Ray, R. M. Mason, and J. R. Levick. Hyaluronan secretion into the synovial cavity of rabbit knees and comparison with albumin turnover. J. Physiol. 503(Pt 3):645–656, 1997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cook, A. D., et al. Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development. Arthritis Res. Ther. 14:R199, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cunnane, G., A. Madigan, E. Murphy, O. FitzGerald, and B. Bresnihan. The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis. Rheumatol. (Oxf.) 40:62–69, 2001.

    Article  CAS  Google Scholar 

  23. Deberg, M., et al. One-year follow-up of Coll2-1, Coll2-1NO2 and myeloperoxydase serum levels in osteoarthritis patients after hip or knee replacement. Ann. Rheum. Dis. 67:168–174, 2008.

    Article  CAS  PubMed  Google Scholar 

  24. Esenyel, M., A. Icagasioglu, and C. Z. Esenyel. Effects of calcitonin on knee osteoarthritis and quality of life. Rheumatol. Int. 33:423–427, 2013.

    Article  CAS  PubMed  Google Scholar 

  25. Fang, H., and F. Beier. Mouse models of osteoarthritis: modelling risk factors and assessing outcomes. Nat. Rev. Rheumatol. 10:413–421, 2014.

    Article  PubMed  Google Scholar 

  26. Felson, D. T. Risk factors for osteoarthritis: understanding joint vulnerability. Clin Orthop Relat Res 427:S16–S21, 2004.

    Article  PubMed  Google Scholar 

  27. Fernandes, J., et al. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritis progression. Am. J. Pathol. 154:1159–1169, 1999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fonseca, J. E., M. J. Santos, H. Canhao, and E. Choy. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun. Rev. 8:538–542, 2009.

    Article  CAS  PubMed  Google Scholar 

  29. Furman, B. D., et al. Joint degeneration following closed intraarticular fracture in the mouse knee: a model of posttraumatic arthritis. J. Orthop. Res. 25:578–592, 2007.

    Article  PubMed  Google Scholar 

  30. Furman, B. D., et al. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis. Arthritis Res. Ther. 16:R134, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ghosh, P., and D. Guidolin. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin. Arthritis Rheum. 32:10–37, 2002.

    Article  CAS  PubMed  Google Scholar 

  32. Goldring, M. B., et al. Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes. J. Clin. Invest. 94:2307–2316, 1994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gouze, E., et al. Lentiviral-mediated gene delivery to synovium: potent intra-articular expression with amplification by inflammation. Mol. Ther. 7:460–466, 2003.

    Article  CAS  PubMed  Google Scholar 

  34. Gupta, M., and G. M. Eisen. NSAIDs and the gastrointestinal tract. Curr. Gastroenterol. Rep. 11:345–353, 2009.

    Article  PubMed  Google Scholar 

  35. Henrotin, Y., M. Marty, and A. Mobasheri. What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis? Maturitas 78:184–187, 2014.

    Article  CAS  PubMed  Google Scholar 

  36. Hochberg, M., X. Chevalier, Y. Henrotin, D. J. Hunter, and D. Uebelhart. Symptom and structure modification in osteoarthritis with pharmaceutical-grade chondroitin sulfate: what’s the evidence? Curr. Med. Res. Opin. 29:259–267, 2013.

    Article  CAS  PubMed  Google Scholar 

  37. Hochberg, M. C., et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthrit Care Res. 64:465–474, 2012.

    Article  CAS  Google Scholar 

  38. Hong, S. L., and L. Levine. Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids. Proc. Natl. Acad. Sci. USA 73:1730–1734, 1976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hootman, J. M., and C. G. Helmick. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum. 54:226–229, 2006.

    Article  PubMed  Google Scholar 

  40. Huang, K., and L. D. Wu. Aggrecanase and aggrecan degradation in osteoarthritis: a review. J. Int. Med. Res. 36:1149–1160, 2008.

    Article  CAS  PubMed  Google Scholar 

  41. Hunter, D. J., and D. T. Felson. Osteoarthritis. Bmj 332:639–642, 2006.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Imamura, M., et al. Concentration of cytokines in patients with osteoarthritis of the knee and fibromyalgia. Clin. Interv. Aging 9:939–944, 2014.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Iqbal, I., and R. Fleischmann. Treatment of osteoarthritis with anakinra. Curr. Rheumatol. Rep. 9:31–35, 2007.

    Article  CAS  PubMed  Google Scholar 

  44. Ismail, H.M. et al. JNK2 controls aggrecan degradation in murine articular cartilage and the development of experimental osteoarthritis. Arthritis Rheumatol., 2015.

  45. Jain, A., et al. Targeting of diacerein loaded lipid nanoparticles to intra-articular cartilage using chondroitin sulfate as homing carrier for treatment of osteoarthritis in rats. Nanomedicine 10:1031–1040, 2014.

    CAS  PubMed  Google Scholar 

  46. Jevsevar, D. S. Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J. Am. Acad. Orthop. Sur. 21:571–576, 2013.

    Google Scholar 

  47. Kang, M. L., and G. I. Im. Drug delivery systems for intra-articular treatment of osteoarthritis. Expert Opin. Drug Deliv. 11:269–282, 2014.

    Article  CAS  PubMed  Google Scholar 

  48. Kang, M. L., J. Y. Ko, J. E. Kim, and G. I. Im. Intra-articular delivery of kartogenin-conjugated chitosan nano/microparticles for cartilage regeneration. Biomaterials 35:9984–9994, 2014.

    Article  CAS  PubMed  Google Scholar 

  49. Kawashima, H., et al. Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to L-selectin, P-selectin, and CD44. J. Biol. Chem. 275:35448–35456, 2000.

    Article  CAS  PubMed  Google Scholar 

  50. Kay, J. D., et al. Intra-articular gene delivery and expression of interleukin-1Ra mediated by self-complementary adeno-associated virus. J. Gene Med. 11:605–614, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Killian, M. L., et al. Traumatic anterior cruciate ligament tear and its implications on meniscal degradation: a preliminary novel lapine osteoarthritis model. J. Surg. Res. 164:234–241, 2010.

    Article  PubMed  Google Scholar 

  52. Ko, F. C., et al. In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae. Arthritis Rheum. 65:1569–1578, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kon, E., et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 27:1490–1501, 2011.

    Article  PubMed  Google Scholar 

  54. Kruse, D. W. Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe? Curr. Rev. Musculoskelet. Med. 1:227–233, 2008.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lawrence, R. C., et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 41:778–799, 1998.

    Article  CAS  PubMed  Google Scholar 

  56. Little, C. B., et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum. 60:3723–3733, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Loeser, R. F. Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis Rheum. 54:1357–1360, 2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Malemud, C. J. Anticytokine therapy for osteoarthritis: evidence to date. Drugs Aging 27:95–115, 2010.

    Article  CAS  PubMed  Google Scholar 

  59. Martel-Pelletier, J., L. M. Wildi, and J. P. Pelletier. Future therapeutics for osteoarthritis. Bone 51:297–311, 2012.

    Article  CAS  PubMed  Google Scholar 

  60. McCoy, A. M. Animal Models of osteoarthritis: comparisons and key considerations. Vet. Pathol. 52:803–818, 2015.

    Article  CAS  PubMed  Google Scholar 

  61. Meheux, C. J., P. C. McCulloch, D. M. Lintner, K. E. Varner, and J. D. Harris. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy 32:495–505, 2016.

    Article  PubMed  Google Scholar 

  62. Miller, L. E., and J. E. Block. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Clin. Med. Insights. Arthritis. Musculoskelet. Disord. 6:57–63, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Monticone, M. et al. Hyaluronic acid intra-articular Injection and exercise therapy: effects on pain and disability in subjects affected by lower limb joints osteoarthritis. The Italian Society of Physical and Rehabilitation Medicine (SIMFER) systematic review. Eur. J. Phys. Rehabil. Med., 2015.

  64. Moreland, L. W. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res. Ther. 5:54–67, 2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Morgen, M., et al. Nanoparticles for improved local retention after intra-articular injection into the knee joint. Pharm. Res. 30:257–268, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Onur, T. S., et al. Joint instability and cartilage compression in a mouse model of posttraumatic osteoarthritis. J. Orthop. Res. 32:318–323, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Opal, S. M., and V. A. DePalo. Anti-inflammatory cytokines. Chest 117:1162–1172, 2000.

    Article  CAS  PubMed  Google Scholar 

  68. Pelletier, J. P., et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum. 40:1012–1019, 1997.

    Article  CAS  PubMed  Google Scholar 

  69. Perman, V. Clinical Biochemistry of Domestic Animals (3rd ed.). London: Academic Press, 1980.

    Google Scholar 

  70. Pi, Y., et al. Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display. Biomaterials 32:6324–6332, 2011.

    Article  CAS  PubMed  Google Scholar 

  71. Pi, Y., et al. Intra-articular delivery of anti-Hif-2alpha siRNA by chondrocyte-homing nanoparticles to prevent cartilage degeneration in arthritic mice. Gene Ther. 22:439–448, 2015.

    Article  CAS  PubMed  Google Scholar 

  72. Pond, M. J., and G. Nuki. Experimentally-induced osteoarthritis in the dog. Ann. Rheum. Dis. 32:387–388, 1973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Poulet, B., et al. Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions. Osteoarthr. Cartil. 23:940–948, 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rampersad, R. R., et al. S100A9 is not essential for disease expression in an acute (K/BxN) or chronic (CIA) model of inflammatory arthritis. Scand. J. Rheumatol. 38:445–449, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Rothenfluh, D. A., H. Bermudez, C. P. O’Neil, and J. A. Hubbell. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. Nat. Mater. 7:248–254, 2008.

    Article  CAS  PubMed  Google Scholar 

  76. Rousseau, J., and P. Garnero. Biological markers in osteoarthritis. Bone 51:265–277, 2012.

    Article  CAS  PubMed  Google Scholar 

  77. Ryan, S. M., et al. An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis. J. Control Release 167:120–129, 2013.

    Article  CAS  PubMed  Google Scholar 

  78. Saklatvala, J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 322:547–549, 1986.

    Article  CAS  PubMed  Google Scholar 

  79. Singh, A., et al. Nanoengineered particles for enhanced intra-articular retention and delivery of proteins. Adv. Healthc. Mater. 3:1562–1567, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sommer, C., and M. Kress. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci. Lett. 361:184–187, 2004.

    Article  CAS  PubMed  Google Scholar 

  81. Steinbeck, M. J., L. J. Nesti, P. F. Sharkey, and J. Parvizi. Myeloperoxidase and chlorinated peptides in osteoarthritis: potential biomarkers of the disease. J. Orthop. Res. 25:1128–1135, 2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Takagi, H., Y. Asano, N. Yamakawa, I. Matsumoto, and K. Kimata. Annexin 6 is a putative cell surface receptor for chondroitin sulfate chains. J. Cell Sci. 115:3309–3318, 2002.

    CAS  PubMed  Google Scholar 

  83. Wang, F., and X. He. Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: a meta-analysis. Exp. Ther. Med. 9:493–500, 2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Whitmire, R. E., et al. Self-assembling nanoparticles for intra-articular delivery of anti-inflammatory proteins. Biomaterials 33:7665–7675, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Williams, T. J., and M. J. Peck. Role of prostaglandin-mediated vasodilatation in inflammation. Nature 270:530–532, 1977.

    Article  CAS  PubMed  Google Scholar 

  86. Yang, C. C., C. Y. Lin, H. S. Wang, and S. R. Lyu. Matrix metalloproteases and tissue inhibitors of metalloproteinases in medial plica and pannus-like tissue contribute to knee osteoarthritis progression. PLoS ONE 8:e79662, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Yang, S., et al. Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat. Med. 16:687–693, 2010.

    Article  CAS  PubMed  Google Scholar 

  88. Yasuda, T. Cartilage destruction by matrix degradation products. Mod. Rheumatol. 16:197–205, 2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zhang, W., et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann. Rheum. Dis. 64:669–681, 2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhang, W., et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr. Cartil. 16:137–162, 2008.

    Article  CAS  PubMed  Google Scholar 

  91. Zhou, Y., et al. In vivo anti-apoptosis activity of novel berberine-loaded chitosan nanoparticles effectively ameliorates osteoarthritis. Int. Immunopharmacol. 28:34–43, 2015.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the following funding agencies for supporting their research that was discussed in the review: NIH. Grant Numbers: R21-AR064034, R01-AG022021, RC4-AR060546, R01-AG028664, P30-AR046121. The authors would like to thank Dr. Mathias P. Bostrom at Hospital for Special Surgery, New York, for providing a de-identified knee joint image.

Author information

Authors and Affiliations

  1. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853-7501, USA

    Derek T. Holyoak & Marjolein C. H. van der Meulen

  2. Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, 14853-7501, USA

    Ye F. Tian, Marjolein C. H. van der Meulen & Ankur Singh

Authors
  1. Derek T. Holyoak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ye F. Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marjolein C. H. van der Meulen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ankur Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Marjolein C. H. van der Meulen or Ankur Singh.

Additional information

Associate Editor Akhilesh K Gaharwar oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Holyoak, D.T., Tian, Y.F., van der Meulen, M.C.H. et al. Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment. Ann Biomed Eng 44, 2062–2075 (2016). https://doi.org/10.1007/s10439-016-1600-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-016-1600-z

Keywords

Search

Navigation