Advertisement

Modulating Innate Inflammatory Reactions in the Application of Orthopedic Biomaterials

  • Tzuhua Lin
  • Eemeli Jämsen
  • Laura Lu
  • Karthik Nathan
  • Jukka Pajarinen
  • Stuart B. Goodman
Chapter

Abstract

Orthopaedic biomaterials are used in a wide variety of surgical procedures including total joint replacement, spine reconstruction, and fracture repair. Despite the development of materials with enhanced mechanical and biological properties, the attachment of an implant to the surrounding bone is still occasionally lost and revision surgery is required in some of the patients with prolonged implantation of orthopaedic biomaterials. The macrophage-associated innate immune response plays a crucial role both in the successful integration and potential rejection of the implant. Acute inflammation is essential for the successful osseointegration and bone regeneration around the implants. Chronic inflammation, on the other hand, is associated with impaired bone formation and osteolysis in the presence of excessive macrophage infiltration and pro-inflammatory cytokine secretion. Here we summarize the current development of immunomodulating strategies to improve the application of orthopaedic biomaterials. The potential drug delivery and controlled release methods that could be applied to administrate immunomodulatory biomolecules are also discussed. In summary, modulations of the innate immune response with the goal of sequential transition from a pro-inflammatory to an anti-inflammatory reaction provides a promising strategy for successful bone regeneration and implant osseointegration.

Keywords

Orthopedic biomaterials Inflammation Macrophage polarization Immunomodulation Wear particles Osteolysis Bone remodeling Tissue engineering Mesenchymal stem cell Osteoblast Osteoclast NF-kB 

Abbreviations

CCL2

C-C motif chemokine ligand 2

FBGC

Foreign-body giant cell

GM-CSF

Granulocyte macrophage colony-stimulating factor

IFN-γ

Interferon gamma

IL

Interleukin

LPS

Lipopolysaccharide

M-CSF

Macrophage colony-stimulating factor

MSC

Mesenchymal stem cell

ODN

Oligodeoxynucleotide

OPG

Osteoprotegerin

PAMP

Pathogen-associated molecular pattern

PDGF

Platelet-derived growth factor

PGA

Poly-glycolic-acid

PLA

Poly-lactic-acid

PLGA

Poly-lactic-glycolic-acid

PRR

Pattern-recognition receptor

RANKL

Receptor-activator of NF-κB ligand

RNAi

RNA interference

TGF-β

Transforming growth factor-β

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor-α

VEGF

Vascular endothelial growth factor

Notes

Acknowledgement

This work was supported by NIH grants 2R01AR055650, 1R01AR063717 and the Ellenburg Chair in Surgery at Stanford University. J. P. was supported by a grant from the Jane and Aatos Erkko foundation.

The authors have no conflicts of interest to declare.

References

  1. 1.
    Global Alliance for Musculoskeletal Health. Key facts from the global burden of disease. 2012, http://bjdonline.org/key-facts-and-figures/.
  2. 2.
    Navarro M, Michiardi A, Castano O, Planell JA. Biomaterials in orthopaedics. J R Soc Interface. 2008;5(27):1137–58.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Drees P, Eckardt A, Gay RE, Gay S, Huber LC. Mechanisms of disease: molecular insights into aseptic loosening of orthopedic implants. Nat Clin Pract Rheumatol. 2007;3(3):165–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Cobelli N, Scharf B, Crisi GM, Hardin J, Santambrogio L. Mediators of the inflammatory response to joint replacement devices. Nat Rev Rheumatol. 2011;7(10):600–8.PubMedCrossRefGoogle Scholar
  5. 5.
    LBHN Service. Joint replacements in U.S. exceed 1 million a year, Pittsburgh Post-Gazette, Pittburgh Post-Gazette. 2013. http://www.post-gazette.com/news/health/2013/03/04/Joint-replacements-in-U-S-exceed.
  6. 6.
    Lewallen EA, Riester SM, Bonin CA, Kremers HM, Dudakovic A, Kakar S, Cohen RC, Westendorf JJ, Lewallen DG, van Wijnen AJ. Biological strategies for improved osseointegration and osteoinduction of porous metal orthopedic implants. Tissue Eng Part B Rev. 2015;21(2):218–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Vitkov L, Hartl D, Hannig M. Is osseointegration inflammation-triggered? Med Hypotheses. 2016;93:1–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Ma QL, Zhao LZ, Liu RR, Jin BQ, Song W, Wang Y, Zhang YS, Chen LH, Zhang YM. Improved implant osseointegration of a nanostructured titanium surface via mediation of macrophage polarization. Biomaterials. 2014;35(37):9853–67.PubMedCrossRefGoogle Scholar
  9. 9.
    Gibon E, Amanatullah DF, Loi F, Pajarinen J, Nabeshima A, Yao Z, Hamadouche M, Goodman SB. The biological response to orthopaedic implants for joint replacement: part I: metals. J Biomed Mater Res B Appl Biomater. 2017;105(7):2162–73.PubMedCrossRefGoogle Scholar
  10. 10.
    Lin TH, Tamaki Y, Pajarinen J, Waters HA, Woo DK, Yao Z, Goodman SB. Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-kappaB as a therapeutic target. Acta Biomater. 2014;10(1):1–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol. 2008;20(2):86–100.PubMedCrossRefGoogle Scholar
  12. 12.
    Goodman SB. Wear particles, periprosthetic osteolysis and the immune system. Biomaterials. 2007;28(34):5044–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Nich C, Takakubo Y, Pajarinen J, Ainola M, Salem A, Sillat T, Rao AJ, Raska M, Tamaki Y, Takagi M, Konttinen YT, Goodman SB, Gallo J. Macrophages-key cells in the response to wear debris from joint replacements. J Biomed Mater Res A. 2013;101:3033.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Ingham E, Fisher J. The role of macrophages in osteolysis of total joint replacement. Biomaterials. 2005;26(11):1271–86.PubMedCrossRefGoogle Scholar
  15. 15.
    Fujiwara N, Kobayashi K. Macrophages in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4(3):281–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958–69.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Davies LC, Jenkins SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat Immunol. 2013;14(10):986–95.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240–73.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol. 2010;11(5):373–84.PubMedCrossRefGoogle Scholar
  20. 20.
    Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8(4):279–89.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11(11):762–74.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011;11(11):723–37.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44(3):450–62.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Lech M, Anders HJ. Macrophages and fibrosis: how resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochim Biophys Acta. 2013;1832(7):989–97.PubMedCrossRefGoogle Scholar
  25. 25.
    Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarization. Front Biosci. 2008;13:453–61.PubMedCrossRefGoogle Scholar
  26. 26.
    Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage M1–M2 polarization balance. Front Immunol. 2014;5:614.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Franz S, Rammelt S, Scharnweber D, Simon JC. Immune responses to implants—a review of the implications for the design of immunomodulatory biomaterials. Biomaterials. 2011;32(28):6692–709.PubMedCrossRefGoogle Scholar
  28. 28.
    Maitra R, Clement CC, Scharf B, Crisi GM, Chitta S, Paget D, Purdue PE, Cobelli N, Santambrogio L. Endosomal damage and TLR2 mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis. Mol Immunol. 2009;47(2–3):175–84.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Caicedo MS, Desai R, McAllister K, Reddy A, Jacobs JJ, Hallab NJ. Soluble and particulate co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. J Orthop Res. 2009;27(7):847–54.PubMedCrossRefGoogle Scholar
  30. 30.
    Sridharan R, Cameron AR, Kelly DJ, Kearney CJ, O’Brien FJ. Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Mater Today. 2015;18(6):313–25.CrossRefGoogle Scholar
  31. 31.
    Goodman SB, Gibon E, Yao Z. The basic science of periprosthetic osteolysis. Instr Course Lect. 2013;62:201–6.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Purdue PE, Koulouvaris P, Potter HG, Nestor BJ, Sculco TP. The cellular and molecular biology of periprosthetic osteolysis. Clin Orthop Relat Res. 2007;454:251–61.PubMedCrossRefGoogle Scholar
  33. 33.
    Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA. 2004;292(4):490–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Chen Z, Klein T, Murray RZ, Crawford R, Chang J, Wu C, Xiao Y. Osteoimmunomodulation for the development of advanced bone biomaterials. Mater Today. 2016;19(6):304–21.CrossRefGoogle Scholar
  35. 35.
    Goodman SB, Gibon E, Pajarinen J, Lin TH, Keeney M, Ren PG, Nich C, Yao Z, Egashira K, Yang F, Konttinen YT. Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. J R Soc Interface. 2014;11(93):20130962.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Brown BN, Ratner BD, Goodman SB, Amar S, Badylak SF. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials. 2012;33(15):3792–802.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Morais JM, Papadimitrakopoulos F, Burgess DJ. Biomaterials/tissue interactions: possible solutions to overcome foreign body response. AAPS J. 2010;12(2):188–96.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hosgood G. Wound healing. The role of platelet-derived growth factor and transforming growth factor beta. Vet Surg. 1993;22(6):490–5.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Wang Y, Wu NN, Mou YQ, Chen L, Deng ZL. Inhibitory effects of recombinant IL-4 and recombinant IL-13 on UHMWPE-induced bone destruction in the murine air pouch model. J Surg Res. 2013;180(2):e73–81.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Rao AJ, Nich C, Dhulipala LS, Gibon E, Valladares R, Zwingenberger S, Smith RL, Goodman SB. Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. J Biomed Mater Res A. 2013;101((7):1926–34.CrossRefGoogle Scholar
  41. 41.
    Sato T, Pajarinen J, Behn A, Jiang X, Lin TH, Loi F, Yao Z, Egashira K, Yang F, Goodman SB. The effect of local IL-4 delivery or CCL2 blockade on implant fixation and bone structural properties in a mouse model of wear particle induced osteolysis. J Biomed Mater Res A. 2016;104(9):2255–62.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Minardi S, Corradetti B, Taraballi F, Byun JH, Cabrera F, Liu X, Ferrari M, Weiner BK, Tasciotti E. IL-4 release from a biomimetic scaffold for the temporally controlled modulation of macrophage response. Ann Biomed Eng. 2016;44(6):2008–19.PubMedCrossRefGoogle Scholar
  43. 43.
    Spiller KL, Nassiri S, Witherel CE, Anfang RR, Ng J, Nakazawa KR, Yu T, Vunjak-Novakovic G. Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials. 2015;37:194–207.PubMedCrossRefGoogle Scholar
  44. 44.
    Hachim D, LoPresti ST, Yates CC, Brown BN. Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration. Biomaterials. 2017;112:95–107.PubMedCrossRefGoogle Scholar
  45. 45.
    Hess K, Ushmorov A, Fiedler J, Brenner RE, Wirth T. TNFalpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappaB signaling pathway. Bone. 2009;45(2):367–76.PubMedCrossRefGoogle Scholar
  46. 46.
    Gilbert L, He X, Farmer P, Boden S, Kozlowski M, Rubin J, Nanes MS. Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology. 2000;141(11):3956–64.PubMedCrossRefGoogle Scholar
  47. 47.
    Childs LM, Goater JJ, O'Keefe RJ, Schwarz EM. Efficacy of etanercept for wear debris-induced osteolysis. J Bone Miner Res. 2001;16(2):338–47.PubMedCrossRefGoogle Scholar
  48. 48.
    Schwarz EM, Campbell D, Totterman S, Boyd A, O'Keefe RJ, Looney RJ. Use of volumetric computerized tomography as a primary outcome measure to evaluate drug efficacy in the prevention of peri-prosthetic osteolysis: a 1-year clinical pilot of etanercept vs. placebo. J Orthop Res. 2003;21(6):1049–55.PubMedCrossRefGoogle Scholar
  49. 49.
    Dong L, Wang R, Zhu YA, Wang C, Diao H, Zhang C, Zhao J, Zhang J. Antisense oligonucleotide targeting TNF-alpha can suppress Co-Cr-Mo particle-induced osteolysis. J Orthop Res. 2008;26(8):1114–20.PubMedCrossRefGoogle Scholar
  50. 50.
    Lin TH, Pajarinen J, Lu L, Nabeshima A, Cordova LA, Yao Z, Goodman SB. NF-kappaB as a therapeutic target in inflammatory-associated bone diseases. Adv Protein Chem Struct Biol. 2017;107:117–54.PubMedCrossRefGoogle Scholar
  51. 51.
    Lin TH, Pajarinen J, Sato T, Loi F, Fan C, Cordova LA, Nabeshima A, Gibon E, Zhang R, Yao Z, Goodman SB. NF-kappaB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model. Acta Biomater. 2016;41:273–81.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Sato T, Pajarinen J, Lin TH, Tamaki Y, Loi F, Egashira K, Yao Z, Goodman SB. NF-kappaB decoy oligodeoxynucleotide inhibits wear particle-induced inflammation in a murine calvarial model. J Biomed Mater Res A. 2015;103(12):3872–8.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Nabeshima A, Pajarinen J, Lin TH, Jiang X, Gibon E, Cordova LA, Loi F, Lu L, Jamsen E, Egashira K, Yang F, Yao Z, Goodman SB. Mutant CCL2 protein coating mitigates wear particle-induced bone loss in a murine continuous polyethylene infusion model. Biomaterials. 2017;117:1–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Keeney M, Waters H, Barcay K, Jiang X, Yao Z, Pajarinen J, Egashira K, Goodman SB, Yang F. Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response. Biomaterials. 2013;34(38):10287–95.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Gerstenfeld L, Cho TJ, Kon T, Aizawa T, Tsay A, Fitch J, Barnes G, Graves D, Einhorn T. Impaired fracture healing in the absence of TNF-α signaling: the role of TNF-α in endochondral cartilage resorption. J Bone Miner Res. 2003;18(9):1584–92.PubMedCrossRefGoogle Scholar
  56. 56.
    Gerstenfeld L, Cho T-J, Kon T, Aizawa T, Cruceta J, Graves B, Einhorn T. Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-alpha signaling. Cells Tissues Organs. 2001;169(3):285–94.PubMedCrossRefGoogle Scholar
  57. 57.
    Yang X, Ricciardi BF, Hernandez-Soria A, Shi Y, Camacho NP, Bostrom MP. Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice. Bone. 2007;41(6):928–36.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Glass GE, Chan JK, Freidin A, Feldmann M, Horwood NJ, Nanchahal J. TNF-α promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc Natl Acad Sci. 2011;108(4):1585–90.PubMedCrossRefGoogle Scholar
  59. 59.
    Xing Z, Lu C, Hu D, Yu Y-y, Wang X, Colnot C, Nakamura M, Wu Y, Miclau T, Marcucio RS. Multiple roles for CCR2 during fracture healing. Dis Model Mech. 2010;3(7–8):451–8.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem. 2003;88(5):873–84.PubMedCrossRefGoogle Scholar
  61. 61.
    Kon T, Cho TJ, Aizawa T, Yamazaki M, Nooh N, Graves D, Gerstenfeld LC, Einhorn TA. Expression of osteoprotegerin, receptor activator of NF-κB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J Bone Miner Res. 2001;16(6):1004–14.PubMedCrossRefGoogle Scholar
  62. 62.
    Mountziaris PM, Mikos AG. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng Part B Rev. 2008;14(2):179–86.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Luttikhuizen DT, Harmsen MC, Luyn MJV. Cellular and molecular dynamics in the foreign body reaction. Tissue Eng. 2006;12(7):1955–70.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Nicolaidou V, Wong MM, Redpath AN, Ersek A, Baban DF, Williams LM, Cope AP, Horwood NJ. Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation. PLoS One. 2012;7(7):e39871.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Guihard P, Danger Y, Brounais B, David E, Brion R, Delecrin J, Richards CD, Chevalier S, Rédini F, Heymann D. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling. Stem Cells. 2012;30(4):762–72.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Spiller KL, Anfang RR, Spiller KJ, Ng J, Nakazawa KR, Daulton JW, Vunjak-Novakovic G. The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials. 2014;35(15):4477–88.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Lu LY, Loi F, Nathan K, Lin Th, Pajarinen J, Gibon E, Nabeshima A, Cordova L, Jämsen E, Yao Z. Pro-inflammatory M1 macrophages promote Osteogenesis by mesenchymal stem cells via the COX-2-prostaglandin E2 pathway. J Orthop Res. 2017;35:2378.PubMedCrossRefGoogle Scholar
  68. 68.
    Raggatt LJ, Wullschleger ME, Alexander KA, Wu ACK, Millard SM, Kaur S, Maugham ML, Gregory LS, Steck R, Pettit AR. Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early Endochondral ossification. Am J Pathol. 2014;184(12):3192–204.PubMedCrossRefGoogle Scholar
  69. 69.
    Schlundt C, El Khassawna T, Serra A, Dienelt A, Wendler S, Schell H, van Rooijen N, Radbruch A, Lucius R, Hartmann S, Duda GN, Schmidt-Bleek K. Macrophages in bone fracture healing: their essential role in endochondral ossification. Bone. 2018;106:78–89.PubMedCrossRefGoogle Scholar
  70. 70.
    Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.CrossRefPubMedGoogle Scholar
  71. 71.
    Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011;42(6):551–5.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol. 2012;8(3):133–43.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Kumar VA, Taylor NL, Shi S, Wickremasinghe NC, D'Souza RN, Hartgerink JD. Self-assembling multidomain peptides tailor biological responses through biphasic release. Biomaterials. 2015;52:71–8.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Rostam H, Singh S, Vrana N, Alexander M, Ghaemmaghami A. Impact of surface chemistry and topography on the function of antigen presenting cells. Biomater Sci. 2015;3(3):424–41.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Rostam HM, Singh S, Salazar F, Magennis P, Hook A, Singh T, Vrana NE, Alexander MR, Ghaemmaghami AM. The impact of surface chemistry modification on macrophage polarisation. Immunobiology. 2016;221(11):1237–46.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Goodman SB, Yao Z, Keeney M, Yang F. The future of biologic coatings for orthopaedic implants. Biomaterials. 2013;34(13):3174–83.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Tobin EJ. Recent coating developments for combination devices in orthopedic and dental applications: a literature review. Adv Drug Deliv Rev. 2017;112:88.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Agarwal R, Garcia AJ. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv Drug Deliv Rev. 2015;94:53–62.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Friedrich EE, Sun LT, Natesan S, Zamora DO, Christy RJ, Washburn NR. Effects of hyaluronic acid conjugation on anti-TNF-alpha inhibition of inflammation in burns. J Biomed Mater Res A. 2014;102(5):1527–36.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Haney EF, Hancock RE. Peptide design for antimicrobial and immunomodulatory applications. Biopolymers. 2013;100(6):572–83.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Hilchie AL, Wuerth K, Hancock RE. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. Nat Chem Biol. 2013;9(12):761–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Clohisy JC, Hirayama T, Frazier E, Han SK, Abu-Amer Y. NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis. J Orthop Res. 2004;22(1):13–20.PubMedCrossRefGoogle Scholar
  83. 83.
    Matsiko A, Levingstone TJ, O'Brien FJ, Gleeson JP. Addition of hyaluronic acid improves cellular infiltration and promotes early-stage chondrogenesis in a collagen-based scaffold for cartilage tissue engineering. J Mech Behav Biomed Mater. 2012;11:41–52.PubMedCrossRefGoogle Scholar
  84. 84.
    Raftery R, O'Brien FJ, Cryan SA. Chitosan for gene delivery and orthopedic tissue engineering applications. Molecules. 2013;18(5):5611–47.PubMedCrossRefGoogle Scholar
  85. 85.
    Raftery RM, Tierney EG, Curtin CM, Cryan SA, O'Brien FJ. Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds. J Control Release. 2015;210:84–94.PubMedCrossRefGoogle Scholar
  86. 86.
    Tierney EG, Duffy GP, Hibbitts AJ, Cryan SA, O'Brien FJ. The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds. J Control Release. 2012;158(2):304–11.PubMedCrossRefGoogle Scholar
  87. 87.
    Schatzlein AG, Zinselmeyer BH, Elouzi A, Dufes C, Chim YT, Roberts CJ, Davies MC, Munro A, Gray AI, Uchegbu IF. Preferential liver gene expression with polypropylenimine dendrimers. J Control Release. 2005;101(1–3):247–58.PubMedCrossRefGoogle Scholar
  88. 88.
    Raftery RM, Walsh DP, Castano IM, Heise A, Duffy GP, Cryan SA, O'Brien FJ. Delivering nucleic-acid based Nanomedicines on biomaterial scaffolds for orthopedic tissue repair: challenges, progress and future perspectives. Adv Mater. 2016;28(27):5447–69.PubMedCrossRefGoogle Scholar
  89. 89.
    Huang CL, Leblond AL, Turner EC, Kumar AH, Martin K, Whelan D, O'Sullivan DM, Caplice NM. Synthetic chemically modified mrna-based delivery of cytoprotective factor promotes early cardiomyocyte survival post-acute myocardial infarction. Mol Pharm. 2015;12(3):991–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Deng Y, Bi X, Zhou H, You Z, Wang Y, Gu P, Fan X. Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds. Eur Cell Mater. 2014;27:13–24. discussion 24-5.PubMedCrossRefGoogle Scholar
  91. 91.
    Zhang M, Gao Y, Caja K, Zhao B, Kim JA. Non-viral nanoparticle delivers small interfering RNA to macrophages in vitro and in vivo. PLoS One. 2015;10(3):e0118472.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Sheedy FJ. Turning 21: induction of miR-21 as a key switch in the inflammatory response. Front Immunol. 2015;6:19.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Boehler R, Kuo R, Shin S, Goodman A, Pilecki M, Leonard J, Shea L. Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype. Biotechnol Bioeng. 2014;111(6):1210–21.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Li Y, Fan L, Liu S, Liu W, Zhang H, Zhou T, Wu D, Yang P, Shen L, Chen J, Jin Y. The promotion of bone regeneration through positive regulation of angiogenic-osteogenic coupling using microRNA-26a. Biomaterials. 2013;34(21):5048–58.PubMedCrossRefGoogle Scholar
  95. 95.
    Benimetskaya L, Loike JD, Khaled Z, Loike G, Silverstein SC, Cao L, el Khoury J, Cai TQ, Stein CA. Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein. Nat Med. 1997;3(4):414–20.PubMedCrossRefGoogle Scholar
  96. 96.
    Kaminska B. MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta. 2005;1754(1–2):253–62.PubMedCrossRefGoogle Scholar
  97. 97.
    Purdue PE, Koulouvaris P, Nestor BJ, Sculco TP. The central role of wear debris in periprosthetic osteolysis. HSS J. 2006;2(2):102–13.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Miyanishi K, Trindade MC, Ma T, Goodman SB, Schurman DJ, Smith RL. Periprosthetic osteolysis: induction of vascular endothelial growth factor from human monocyte/macrophages by orthopaedic biomaterial particles. J Bone Miner Res. 2003;18(9):1573–83.PubMedCrossRefGoogle Scholar
  99. 99.
    Ren K, Dusad A, Yuan F, Yuan H, Purdue PE, Fehringer EV, Garvin KL, Goldring SR, Wang D. Macromolecular prodrug of dexamethasone prevents particle-induced peri-implant osteolysis with reduced systemic side effects. J Control Release. 2014;175:1–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Urbanska J, Karewicz A, Nowakowska M. Polymeric delivery systems for dexamethasone. Life Sci. 2014;96(1–2):1–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Webber MJ, Matson JB, Tamboli VK, Stupp SI. Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response. Biomaterials. 2012;33(28):6823–32.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Wadhwa R, Lagenaur CF, Cui XT. Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode. J Control Release. 2006;110(3):531–41.PubMedCrossRefGoogle Scholar
  103. 103.
    Zhang S, Ermann J, Succi MD, Zhou A, Hamilton MJ, Cao B, Korzenik JR, Glickman JN, Vemula PK, Glimcher LH, Traverso G, Langer R, Karp JM. An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease. Sci Transl Med. 2015;7(300):300ra128.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Francois M, Romieu-Mourez R, Li M, Galipeau J. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther. 2012;20(1):187–95.PubMedCrossRefGoogle Scholar
  106. 106.
    Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2(2):141–50.PubMedCrossRefGoogle Scholar
  107. 107.
    Choi JJ, Yoo SA, Park SJ, Kang YJ, Kim WU, Oh IH, Cho CS. Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice. Clin Exp Immunol. 2008;153(2):269–76.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Tan CQ, Gao X, Guo L, Huang H. Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of autoimmune sensorineural hearing loss in a Guinea pig model. Biomed Res Int. 2014;2014:856019.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Pajarinen J, Lin TH, Nabeshima A, Jamsen E, Lu L, Nathan K, Yao Z, Goodman SB. Mesenchymal stem cells in the aseptic loosening of total joint replacements. J Biomed Mater Res A. 2017;105(4):1195–207.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013;13(4):392–402.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012;12(5):383–96.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Rosenbaum AJ, Grande DA, Dines JS. The use of mesenchymal stem cells in tissue engineering: a global assessment. Organogenesis. 2008;4(1):23–7.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Han LH, Conrad B, Chung MT, Deveza L, Jiang X, Wang A, Butte MJ, Longaker MT, Wan D, Yang F. Winner of the young investigator award of the Society for Biomaterials at the 10th world biomaterials congress, may 17-22, 2016, Montreal QC, Canada: microribbon-based hydrogels accelerate stem cell-based bone regeneration in a mouse critical-size cranial defect model. J Biomed Mater Res A. 2016;104(6):1321–31.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Uebersax L, Hagenmuller H, Hofmann S, Gruenblatt E, Muller R, Vunjak-Novakovic G, Kaplan DL, Merkle HP, Meinel L. Effect of scaffold design on bone morphology in vitro. Tissue Eng. 2006;12(12):3417–29.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell. 2009;4(3):206–16.PubMedCrossRefGoogle Scholar
  116. 116.
    Guan M, Yao W, Liu R, Lam KS, Nolta J, Jia J, Panganiban B, Meng L, Zhou P, Shahnazari M, Ritchie RO, Lane NE. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med. 2012;18(3):456–62.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Tzuhua Lin
    • 1
  • Eemeli Jämsen
    • 1
  • Laura Lu
    • 1
  • Karthik Nathan
    • 1
  • Jukka Pajarinen
    • 1
  • Stuart B. Goodman
    • 1
    • 2
  1. 1.Departments of Orthopedic SurgeryStanford University School of MedicineRedwood CityUSA
  2. 2.Department of BioengineeringStanford UniversityStanfordUSA

Personalised recommendations