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A multifunctional dexamethasone-delivery implant fabricated using atmospheric plasma and its effects on apoptosis, osteogenesis and inflammation

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Abstract

Implant-based local drug delivery is a unique surgical therapy with many clinical advantages. Atmospheric pressure plasma is a novel non-thermal surface biotechnology that has only recently been applied in enhancing a surgical implant. We are the first to use this technology to successfully create a dexamethasone-delivery metallic implant. Irrespective of the loaded medication, the surface of this novel implant possesses advantageous material features including homogeneity, hydrophilicity, and optimal roughness. UV-vis spectroscopy revealed much more sustainable drug release compared to the implants produced using simple drug attachment. In addition, our drug-releasing implant was found to have multiple biological benefits. As proven by the ELISA data, this multi-layer drug complex provides differential regulation on the cell apoptosis, as well as pro-osteogenic and anti-inflammatory effects on the peri-implant tissue. Furthermore, using the pathway-specific PCR array, our study discovered 28 and 26 upregulated and downregulated genes during osteogenesis and inflammation on our newly fabricated drug-delivery implant, respectively. The medication-induced change in molecular profile serves as a promising clue for designing future implant-based therapy. Collectively, we present atmospheric pressure plasma as a potent tool for creating a surgical implant-based drug-delivery system, which renders multiple therapeutic potentials.

Schematic of the APP-facilitated Dex-delivery implant. This layer-by-layer drug-releasing complex consisted of bottom plasma activation layer, middle medication layer, and top absorbable polymer layer.

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References

  1. Dimitriadis PA, Farr MR, Allam A, Ray J. Three year experience with the cochlear BAHA attract implant: a systematic review of the literature. BMC Ear Nose Throat Disord. 2016;16:12.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Parithimarkalaignan S, Padmanabhan TV. Osseointegration: an update. J Indian Prosthodont Soc. 2013;13(1):2–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shapiro S, Ramadan J, Cassis A. BAHA skin complications in the pediatric population: systematic review with meta-analysis, otology & neurotology : official publication of the American Otological Society. Otol Neurotol. 2018;39(7):865–73.

    Article  PubMed  Google Scholar 

  4. Greenhalgh DG. The role of apoptosis in wound healing. Int J Biochem Cell Biol. 1998;30(9):1019–30.

    Article  CAS  PubMed  Google Scholar 

  5. Campos PP, Andrade SP, Moro L, Ferreira MA, Vasconcelos AC. Cellular proliferation, differentiation and apoptosis in polyether-polyurethane sponge implant model in mice. Histol Histopathol. 2006;21(12):1263–70.

    CAS  PubMed  Google Scholar 

  6. Jia H, Wang J, Francois F, Uziel A, Puel JL, Venail F. Molecular and cellular mechanisms of loss of residual hearing after cochlear implantation. Ann Otol Rhinol Laryngol. 2013;122(1):33–9.

    Article  PubMed  Google Scholar 

  7. Stea S, Visentin M, Granchi D, Cenni E, Ciapetti G, Sudanese A, et al. Apoptosis in peri-implant tissue. Biomaterials. 2000;21(13):1393–8.

    Article  CAS  PubMed  Google Scholar 

  8. Tan F, Walshe P, Viani L, Al-Rubeai M. Surface biotechnology for refining cochlear implants. Trends Biotechnol. 2013;31(12):678–87.

    Article  CAS  PubMed  Google Scholar 

  9. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Park JB. The effects of dexamethasone, ascorbic acid, and beta-glycerophosphate on osteoblastic differentiation by regulating estrogen receptor and osteopontin expression. J Surg Res. 2012;173(1):99–104.

    Article  CAS  PubMed  Google Scholar 

  11. Song IH, Caplan AI, Dennis JE. In vitro dexamethasone pretreatment enhances bone formation of human mesenchymal stem cells in vivo. J Orthop Res. 2009;27(7):916–21.

    Article  CAS  PubMed  Google Scholar 

  12. Wang Q, Wang J, Lu Q, Detamore MS, Berkland C. Injectable PLGA based colloidal gels for zero-order dexamethasone release in cranial defects. Biomaterials. 2010;31(18):4980–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhong Y, McConnell GC, Ross JD, DeWeerth SP, Bellamkonda RV, A novel dexamethasone-releasing, anti-inflammatory coating for neural implants, Conference Proceedings. 2nd International IEEE EMBS Conference on Neural Engineering, 2005., 2005, pp. 522–525.

  14. Santos A, Sinn Aw M, Bariana M, Kumeria T, Wang Y, Losic D. Drug-releasing implants: current progress, challenges and perspectives. J Mater Chem B. 2014;2(37):6157–82.

    Article  CAS  PubMed  Google Scholar 

  15. Trajkovski B, Petersen A, Strube P, Mehta M, Duda GN. Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone. Adv Drug Deliv Rev. 2012;64(12):1142–51.

    Article  CAS  PubMed  Google Scholar 

  16. Xuereb M, Camilleri J, Attard NJ. Systematic review of current dental implant coating materials and novel coating techniques. Int J Prosthodont. 2015;28(1):51–9.

    Article  PubMed  Google Scholar 

  17. Heinlin J, Isbary G, Stolz W, Morfill G, Landthaler M, Shimizu T, et al. Plasma applications in medicine with a special focus on dermatology. J Eur Acad Dermatol Venereol. 2011;25(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  18. Metcalfe C, Muzaffar J, Daultrey C, Coulson C. Coblation tonsillectomy: a systematic review and descriptive analysis. Eur Arch Otorhinolaryngol. 2017;274(6):2637–47.

    Article  PubMed  Google Scholar 

  19. Tan F, O’Neill F, Naciri M, Dowling D, Al-Rubeai M. Cellular and transcriptomic analysis of human mesenchymal stem cell response to plasma-activated hydroxyapatite coating. Acta Biomater. 2012;8(4):1627–38.

    Article  CAS  PubMed  Google Scholar 

  20. Prasad BR, Brook MA, Smith T, Zhao S, Chen Y, Sheardown H, et al. Controlling cellular activity by manipulating silicone surface roughness, colloids and surfaces. Colloids Surf B Biointerfaces. 2010;78(2):237–42.

    Article  CAS  PubMed  Google Scholar 

  21. Dowling DP, Ramamoorthy A, Rahman M, Mooney DA, MacElroy JMD. Influence of atmospheric plasma source and gas composition on the properties of deposited siloxane coatings. Plasma Process Polym. 2009;6(S1):S483–9.

    Article  CAS  Google Scholar 

  22. Tynan J, Ward P, Byrne G, Dowling DP. Deposition of biodegradable polycaprolactone coatings using an in-line atmospheric pressure plasma system. Plasma Process Polym. 2009;6(S1):S51–6.

    Article  CAS  Google Scholar 

  23. Dowling DP, Maher S, Law VJ, Ardhaoui M, Stallard C, Keenan A. Modified drug release using atmospheric pressure plasma deposited siloxane coatings. J Phys D Appl Phys. 2016;49(36):364005.

    Article  CAS  Google Scholar 

  24. Spriano S, Yamaguchi S, Baino F, Ferraris S. A critical review of multifunctional titanium surfaces: new frontiers for improving osseointegration and host response, avoiding bacteria contamination. Acta Biomater. 2018;79:1–22.

    Article  CAS  PubMed  Google Scholar 

  25. Tan F, Naciri M, Dowling D, Al-Rubeai M. In vitro and in vivo bioactivity of CoBlast hydroxyapatite coating and the effect of impaction on its osteoconductivity. Biotechnol Adv. 2012;30(1):352–62.

    Article  CAS  PubMed  Google Scholar 

  26. Dowling DP, Donegan M, Cullen PJ, Law VJ, Milosavljevic V. Importance of plasma thermal energy transfer for plasma jet systems. IEEE Transactions on Plasma Science. 2014;42(10):2426–7.

    Article  CAS  Google Scholar 

  27. Stallard CP, Iqbal MM, Turner MM, Dowling DP Investigation of the formation mechanism of aligned nano-structured siloxane coatings deposited using an atmospheric plasma jet Plasma Process Polym 10(10) 2013 n/a-n/a

  28. Breathnach R, McDonnell KA, Chebbi A, Callanan JJ, Dowling DP. Evaluation of the effectiveness of kINPen Med plasma jet and bioactive agent therapy in a rat model of wound healing. Biointerphases. 2018;13(5):051002.

    Article  PubMed  CAS  Google Scholar 

  29. Kokubo T. Bioactive glass ceramics: properties and applications. Biomaterials. 1991;12(2):155–63.

    Article  CAS  PubMed  Google Scholar 

  30. Forouzandeh A, Hesaraki S, Zamanian A. The releasing behavior and in vitro osteoinductive evaluations of dexamethasone-loaded porous calcium phosphate cements. Ceram Int. 2014;40(1):1081–91.

    Article  CAS  Google Scholar 

  31. Zhang C, Soori M, Miles FL, Sikes RA, Carson DD, Chung LW, et al. Paracrine factors produced by bone marrow stromal cells induce apoptosis and neuroendocrine differentiation in prostate cancer cells. Prostate. 2011;71(2):157–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chrysis D, Zaman F, Chagin AS, Takigawa M, Savendahl L. Dexamethasone induces apoptosis in proliferative chondrocytes through activation of caspases and suppression of the Akt-phosphatidylinositol 3′-kinase signaling pathway. Endocrinology. 2005;146(3):1391–7.

    Article  CAS  PubMed  Google Scholar 

  33. Tan F, Naciri M, Al-Rubeai M. Osteoconductivity and growth factor production by MG63 osteoblastic cells on bioglass-coated orthopedic implants. Biotechnol Bioeng. 2011;108(2):454–64.

    Article  CAS  PubMed  Google Scholar 

  34. Spano A, Barni S, Sciola L. PMA withdrawal in PMA-treated monocytic THP-1 cells and subsequent retinoic acid stimulation, modulate induction of apoptosis and appearance of dendritic cells. Cell Prolif. 2013;46(3):328–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  36. Strnad G, Chirila N, Petrovan C, Russu O. Contact angle measurement on medical implant titanium based biomaterials. Procedia Technology. 2016;22:946–53.

    Article  Google Scholar 

  37. Duske K, Koban I, Kindel E, Schroder K, Nebe B, Holtfreter B, et al. Atmospheric plasma enhances wettability and cell spreading on dental implant metals. J Clin Periodontol. 2012;39(4):400–7.

    Article  CAS  PubMed  Google Scholar 

  38. Yang DH, Yoon SJ, Lee DW. Preparation and evaluation of dexamethasone (DEX)/growth and differentiation factor-5 (GDF-5) surface-modified titanium using beta-cyclodextrin-conjugated heparin (CD-Hep) for enhanced osteogenic activity in vitro and in vivo. Int J Mol Sci. 2017;18(8).

  39. Gittens RA, Scheideler L, Rupp F, Hyzy SL, Geis-Gerstorfer J, Schwartz Z, et al. A review on the wettability of dental implant surfaces II: biological and clinical aspects. Acta Biomater. 2014;10(7):2907–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ponsonnet L, Reybier K, Jaffrezic N, Comte V, Lagneau C, Lissac M, et al. Relationship between surface properties (roughness, wettability) of titanium and titanium alloys and cell behaviour. Mater Sci Eng C. 2003;23(4):551–60.

    Article  CAS  Google Scholar 

  41. Barry JN, Cowley A, McNally PJ, Dowling DP. Influence of substrate metal alloy type on the properties of hydroxyapatite coatings deposited using a novel ambient temperature deposition technique. J Biomed Mater Res A. 2014;102(3):871–9.

    Article  CAS  PubMed  Google Scholar 

  42. Benzon HT, Chew TL, McCarthy RJ, Benzon HA, Walega DR. Comparison of the particle sizes of different steroids and the effect of dilution: a review of the relative neurotoxicities of the steroids. Anesthesiology. 2007;106(2):331–8.

    Article  CAS  PubMed  Google Scholar 

  43. Faia-Torres AB, Charnley M, Goren T, Guimond-Lischer S, Rottmar M, Maniura-Weber K, et al. Osteogenic differentiation of human mesenchymal stem cells in the absence of osteogenic supplements: a surface-roughness gradient study. Acta Biomater. 2015;28:64–75.

    Article  CAS  PubMed  Google Scholar 

  44. Yang JH, Kim KH, You CK, Rautray TR, Kwon TY. Synthesis of spherical hydroxyapatite granules with interconnected pore channels using camphene emulsion. J Biomed Mater Res B Appl Biomater. 2011;99(1):150–7.

    Article  PubMed  CAS  Google Scholar 

  45. Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J. 2001;10(Suppl 2):S96–101.

    PubMed  PubMed Central  Google Scholar 

  46. Araujo JV, Martins A, Leonor IB, Pinho ED, Reis RL, Neves NM. Surface controlled biomimetic coating of polycaprolactone nanofiber meshes to be used as bone extracellular matrix analogues. J Biomater Sci Polym Ed. 2008;19(10):1261–78.

    Article  CAS  PubMed  Google Scholar 

  47. Chen J, Luo Y, Hong L, Ling Y, Pang J, Fang Y, et al. Synthesis, characterization and osteoconductivity properties of bone fillers based on alendronate-loaded poly(epsilon-caprolactone)/hydroxyapatite microspheres. J Mater Sci Mater Med. 2011;22(3):547–55.

    Article  CAS  PubMed  Google Scholar 

  48. von Woedtke T, Reuter S, Masur K, Weltmann KD. Plasmas for medicine. Phys Rep. 2013;530(4):291–320.

    Article  CAS  Google Scholar 

  49. Sarrette J-P, Rouffet B, Ricard A. Determination of nitrogen atoms loss probabilities on copper, aluminium, alumina, brass and nylon surfaces. Plasma Process Polym. 2006;3(2):120–6.

    Article  CAS  Google Scholar 

  50. Kesavan K, Pandit JK, Kant S, Muthu MS. Positively charged microemulsions of dexamethasone: comparative effects of two cosurfactants on ocular drug delivery and bioavailability. Ther Deliv. 2013;4(11):1385–95.

    Article  CAS  PubMed  Google Scholar 

  51. Petlin DG, Tverdokhlebov SI, Anissimov YG. Plasma treatment as an efficient tool for controlled drug release from polymeric materials: a review. J Control Release. 2017;266:57–74.

    Article  CAS  PubMed  Google Scholar 

  52. Bhatt S, Pulpytel J, Mirshahi M, Arefi-Khonsari F. Plasma co-polymerized nano coatings—as a biodegradable solid carrier for tunable drug delivery applications. Polymer. 2013;54(18):4820–9.

    Article  CAS  Google Scholar 

  53. Yoshida S, Hagiwara K, Hasebe T, Hotta A. Surface modification of polymers by plasma treatments for the enhancement of biocompatibility and controlled drug release. Surf Coat Technol. 2013;233(0):99–107.

    Article  CAS  Google Scholar 

  54. Gruver-Yates AL, Cidlowski JA. Tissue-specific actions of glucocorticoids on apoptosis: a double-edged sword. Cells. 2013;2(2):202–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Moutsatsou P, Kassi E, Papavassiliou AG. Glucocorticoid receptor signaling in bone cells. Trends Mol Med. 2012;18(6):348–59.

    Article  CAS  PubMed  Google Scholar 

  56. Li H, Qian W, Weng X, Wu Z, Li H, Zhuang Q, et al. Glucocorticoid receptor and sequential P53 activation by dexamethasone mediates apoptosis and cell cycle arrest of osteoblastic MC3T3-E1 cells. PLoS One. 2012;7(6):e37030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Achuthan A, Aslam ASM, Nguyen Q, Lam PY, Fleetwood AJ, Frye AT, et al. Glucocorticoids promote apoptosis of proinflammatory monocytes by inhibiting ERK activity. Cell Death Dis. 2018;9(3):267.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Zeng S, Qiao H, Lv XW, Fan D, Liu T, Xie D. High-dose dexamethasone induced LPS-stimulated rat alveolar macrophages apoptosis. Drug Des Devel Ther. 2017;11:3097–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ren R, Oakley RH, Cruz-Topete D, Cidlowski JA. Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis. Endocrinology. 2012;153(11):5346–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wen LP, Madani K, Fahrni JA, Duncan SR, Rosen GD. Dexamethasone inhibits lung epithelial cell apoptosis induced by IFN-gamma and Fas. Am J Phys. 1997;273(5):L921–9.

    CAS  Google Scholar 

  61. Smith LK, Cidlowski JA. Glucocorticoid-induced apoptosis of healthy and malignant lymphocytes. Prog Brain Res. 2010;182:1–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gross KL, Oakley RH, Scoltock AB, Jewell CM, Cidlowski JA. Glucocorticoid receptor alpha isoform-selective regulation of antiapoptotic genes in osteosarcoma cells: a new mechanism for glucocorticoid resistance. Mol Endocrinol. 2011;25(7):1087–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Werner SB, Tessler J, Guglielmotti MB, Cabrini RL. Effect of dexamethasone on osseointegration: a preliminary experimental study. J Oral Implantol. 1996;22(3–4):216–9.

    CAS  PubMed  Google Scholar 

  64. Schinke T, Karsenty G. Transcriptional control of osteoblast differentiation and function. In: Bilezikian JP, Raisz LG, Martin TJ, editors. Principles of bone biology. San Diego: Academic Press; 2008. p. 109–19.

    Chapter  Google Scholar 

  65. Setzer B, Bachle M, Metzger MC, Kohal RJ. The gene-expression and phenotypic response of hFOB 1.19 osteoblasts to surface-modified titanium and zirconia. Biomaterials. 2009;30(6):979–90.

    Article  CAS  PubMed  Google Scholar 

  66. Duarte PM, Serrao CR, Miranda TS, Zanatta LC, Bastos MF, Faveri M, et al. Could cytokine levels in the peri-implant crevicular fluid be used to distinguish between healthy implants and implants with peri-implantitis? A systematic review. J Periodontal Res. 2016;51(6):689–98.

    Article  CAS  PubMed  Google Scholar 

  67. Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006;8(Suppl 2):S3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Kzhyshkowska J, Gudima A, Riabov V, Dollinger C, Lavalle P, Vrana NE. Macrophage responses to implants: prospects for personalized medicine. J Leukoc Biol. 2015;98(6):953–62.

    Article  CAS  PubMed  Google Scholar 

  70. Barbosa Saliba J, Vieira L, Fernandes-Cunha GM, Rodrigues Da Silva G, Ligorio Fialho S, Silva-Cunha A, et al. Anti-inflammatory effect of dexamethasone controlled released from anterior suprachoroidal polyurethane implants on endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2016;57(4):1671–9.

    Article  PubMed  CAS  Google Scholar 

  71. Bruderer M, Richards RG, Alini M, Stoddart MJ. Role and regulation of RUNX2 in osteogenesis. Eur Cell Mater. 2014;28:269–86.

    Article  CAS  PubMed  Google Scholar 

  72. Na Y, Heo SJ, Kim SK, Koak JY. Implant surface treatments affect gene expression of Runx2, osteogenic key marker. J Adv Prosthodont. 2009;1(2):91–6.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Schneider GB, Zaharias R, Seabold D, Keller J, Stanford C. Differentiation of preosteoblasts is affected by implant surface microtopographies. J Biomed Mater Res A. 2004;69(3):462–8.

    Article  PubMed  CAS  Google Scholar 

  74. Hata K, Ikebe K, Wada M, Nokubi T. Osteoblast response to titanium regulates transcriptional activity of Runx2 through MAPK pathway. J Biomed Mater Res A. 2007;81(2):446–52.

    Article  PubMed  CAS  Google Scholar 

  75. Phillips JE, Gersbach CA, Wojtowicz AM, Garcia AJ. Glucocorticoid-induced osteogenesis is negatively regulated by Runx2/Cbfa1 serine phosphorylation. J Cell Sci. 2006;119(Pt 3):581–91.

    Article  CAS  PubMed  Google Scholar 

  76. Sinha KM, Zhou X. Genetic and molecular control of osterix in skeletal formation. J Cell Biochem. 2013;114(5):975–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Tu Q, Valverde P, Li S, Zhang J, Yang P, Chen J. Osterix overexpression in mesenchymal stem cells stimulates healing of critical-sized defects in murine calvarial bone. Tissue Eng. 2007;13(10):2431–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Tu Q, Valverde P, Chen J. Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells. Biochem Biophys Res Commun. 2006;341(4):1257–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Rashid H, Ma C, Chen H, Wang H, Hassan MQ, Sinha K, et al. Sp7 and Runx2 molecular complex synergistically regulate expression of target genes. Connect Tissue Res. 2014;55(Suppl 1):83–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Schneider H, Sedaghati B, Naumann A, Hacker MC, Schulz-Siegmund M. Gene silencing of chordin improves BMP-2 effects on osteogenic differentiation of human adipose tissue-derived stromal cells. Tissue Eng A. 2014;20(1–2):335–45.

    Article  CAS  Google Scholar 

  81. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hallab NJ, Jacobs JJ. Chemokines associated with pathologic responses to orthopedic implant debris. Front Endocrinol. 2017;8:5.

    Article  Google Scholar 

  83. McHugh J. Long-term safety of canakinumab in systemic JIA. Nat Rev Rheumatol. 2018;14(11):622.

    PubMed  Google Scholar 

  84. Menten P, Wuyts A, Van Damme J. Macrophage inflammatory protein-1. Cytokine Growth Factor Rev. 2002;13(6):455–81.

    Article  CAS  PubMed  Google Scholar 

  85. Dapunt U, Maurer S, Giese T, Gaida MM, Hansch GM. The macrophage inflammatory proteins MIP1alpha (CCL3) and MIP2alpha (CXCL2) in implant-associated osteomyelitis: linking inflammation to bone degradation. Mediat Inflamm. 2014;2014:728619.

    Article  CAS  Google Scholar 

  86. Varma TK, Toliver-Kinsky TE, Lin CY, Koutrouvelis AP, Nichols JE, Sherwood ER. Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice. Infect Immun. 2001;69(9):5249–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Schierano G, Bellone G, Cassarino E, Pagano M, Preti G, Emanuelli G. Transforming growth factor-beta and interleukin 10 in oral implant sites in humans. J Dent Res. 2003;82(6):428–32.

    Article  CAS  PubMed  Google Scholar 

  88. Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy—review of a new approach. Pharmacol Rev. 2003;55(2):241–69.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank Professor Denis Dowling in UCD Centre for Biomedical Engineering and experts in the National Centre for Plasma Science & Technology.

Funding

This work was sponsored by the Shanghai Pujiang Program (project no. 19PJ1408800). It was initiated by Science Foundation Ireland and Shanghai East Hospital.

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Correspondence to Fei Tan.

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Tan, F., Al-Rubeai, M. A multifunctional dexamethasone-delivery implant fabricated using atmospheric plasma and its effects on apoptosis, osteogenesis and inflammation. Drug Deliv. and Transl. Res. 11, 86–102 (2021). https://doi.org/10.1007/s13346-019-00700-8

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