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Immunomodulation of Biomaterials by Controlling Macrophage Polarization

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Biomimetic Medical Materials

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1064))

Abstract

Macrophages are key players in innate immune responses to foreign substances. They participate in the phagocytosis of biomaterial-derived particles, angiogenesis, recruitment of fibroblasts, and formation of granulation tissues. Most macrophage functions are achieved through the release of various cytokines and chemokines; the release profile of cytokines is dependent on the phenotype of macrophages, namely proinflammatory M1 or antiinflammatory M2. M1 and M2 macrophages coexist during an inflammatory phase, and the M1/M2 ratio is considered to be an important factor for wound-healing or tissue regeneration. This ratio depends on the chemical and physical properties of biomaterials. To obtain a favorable foreign body reaction to biomaterials, the phenotypes of the macrophages can be modulated by cytokines, antibodies, small chemicals, and microRNAs. Geometrical surface fabrication of biomaterials can also be used for modulating the phenotype of macrophages.

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References

  • Akisue T, Bauer TW, Farver CF, Mochida Y (2002) The effect of particle wear debris on nfkappab activation and pro-inflammatory cytokine release in differentiated thp-1 cells. J Biomed Mater Res 59(3):507–515

    Article  CAS  Google Scholar 

  • Almeida CR, Serra T, Oliveira MI, Planell JA, Barbosa MA, Navarro M (2014) Impact of 3-d printed pla- and chitosan-based scaffolds on human monocyte/macrophage responses: unraveling the effect of 3-d structures on inflammation. Acta Biomater 10(2):613–622

    Article  CAS  Google Scholar 

  • Badylak SF, Valentin JE, Ravindra AK, McCabe GP, Stewart-Akers AM (2008) Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A 14(11):1835–1842

    Article  CAS  Google Scholar 

  • Bhardwaj U, Sura R, Papadimitrakopoulos F, Burgess DJ (2010) Plga/pva hydrogel composites for long-term inflammation control following s.C. Implantation. Int J Pharm 384(1–2):78–86

    Article  CAS  Google Scholar 

  • Blaine TA, Rosier RN, Puzas JE, Looney RJ, Reynolds PR, Reynolds SD, O’Keefe RJ (1996) Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger rna in human peripheral blood monocytes due to titanium particles. J Bone Joint Surg Am 78(8):1181–1192

    Article  CAS  Google Scholar 

  • Brown BN, Londono R, Tottey S, Zhang L, Kukla KA, Wolf MT, Daly KA, Reing JE, Badylak SF (2012) Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater 8(3):978–987

    Article  CAS  Google Scholar 

  • Cha BH, Shin SR, Leijten J, Li YC, Singh S, Liu JC, Annabi N, Abdi R, Dokmeci MR, Vrana NE et al (2017) Integrin-mediated interactions control macrophage polarization in 3d hydrogels. Adv Healthc Mater. https://doi.org/10.1002/adhm.201700289

    Article  Google Scholar 

  • Deng B, Wehling-Henricks M, Villalta SA, Wang Y, Tidball JG (2012) IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. J Immunol 189(7):3669–3680

    Article  CAS  Google Scholar 

  • Dondossola E, Holzapfel BM, Alexander S, Filippini S, Hutmacher DW, Friedl P (2016) Examination of the foreign body response to biomaterials by nonlinear intravital microscopy. Nat Biomed Eng 1:0007

    Article  Google Scholar 

  • Feng L, Song P, Zhou H, Li A, Ma Y, Zhang X, Liu H, Xu G, Zhou Y, Wu X et al (2014) Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice. Biochem Pharmacol 89(1):109–118

    Article  CAS  Google Scholar 

  • Feng X, Weng D, Zhou F, Owen YD, Qin H, Zhao J, Wen Y, Huang Y, Chen J, Fu H et al (2016) Activation of pparγ by a natural flavonoid modulator, apigenin ameliorates obesity-related inflammation via regulation of macrophage polarization. EBioMedicine 9:61–76

    Article  Google Scholar 

  • Gao S, Zhou J, Liu N, Wang L, Gao Q, Wu Y, Zhao Q, Liu P, Wang S, Liu Y et al (2015) Curcumin induces m2 macrophage polarization by secretion il-4 and/or il-13. J Mol Cell Cardiol 85:131–139

    Article  CAS  Google Scholar 

  • Giri SN, Hyde DM, Hollinger MA (1993) Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice. Thorax 48(10):959–966

    Article  CAS  Google Scholar 

  • Gower RM, Boehler RM, Azarin SM, Ricci CF, Leonard JN, Shea LD (2014) Modulation of leukocyte infiltration and phenotype in microporous tissue engineering scaffolds via vector induced IL-10 expression. Biomaterials 35(6):2024–2031

    Article  CAS  Google Scholar 

  • Hachim D, LoPresti ST, Yates CC, Brown BN (2017) Shifts in macrophage phenotype at the biomaterial interface via il-4 eluting coatings are associated with improved implant integration. Biomaterials 112:95–107

    Article  CAS  Google Scholar 

  • Hayes EM, Tsaousi A, Di Gregoli K, Jenkinson SR, Bond AR, Johnson JL, Bevan L, Thomas AC, Newby AC (2014) Classical and alternative activation and metalloproteinase expression occurs in foam cell macrophages in male and female apoe null mice in the absence of t and b lymphocytes. Front Immunol 5:537

    Article  Google Scholar 

  • Hernandez-Pando R, Bornstein QL, Aguilar Leon D, Orozco EH, Madrigal VK, Martinez Cordero E (2000) Inflammatory cytokine production by immunological and foreign body multinucleated giant cells. Immunology 100(3):352–358

    Article  CAS  Google Scholar 

  • Heusinkveld M, de Vos van Steenwijk PJ, Goedemans R, Ramwadhdoebe TH, Gorter A, Welters MJ, van Hall T, van der Burg SH (2011) M2 macrophages induced by prostaglandin e2 and il-6 from cervical carcinoma are switched to activated m1 macrophages by cd4+ th1 cells. J Immunol (Baltimore, Md: 1950) 187(3):1157–1165

    Article  CAS  Google Scholar 

  • Hickey T, Kreutzer D, Burgess DJ, Moussy F (2002) In vivo evaluation of a dexamethasone/plga microsphere system designed to suppress the inflammatory tissue response to implantable medical devices. J Biomed Mater Res 61(2):180–187

    Article  CAS  Google Scholar 

  • Im GI, Han JD (2001) Suppressive effects of interleukin-4 and interleukin-10 on the production of proinflammatory cytokines induced by titanium-alloy particles. J Biomed Mater Res 58(5):531–536

    Article  CAS  Google Scholar 

  • Ingham E, Green TR, Stone MH, Kowalski R, Watkins N, Fisher J (2000) Production of tnf-alpha and bone resorbing activity by macrophages in response to different types of bone cement particles. Biomaterials 21(10):1005–1013

    Article  CAS  Google Scholar 

  • Keane TJ, Londono R, Turner NJ, Badylak SF (2012) Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials 33(6):1771–1781

    Article  CAS  Google Scholar 

  • Li B, Hu Y, Zhao Y, Cheng M, Qin H, Cheng T, Wang Q, Peng X, Zhang X (2017) Curcumin attenuates titanium particle-induced inflammation by regulating macrophage polarization in vitro and in vivo. Front Immunol 8:55

    PubMed  PubMed Central  Google Scholar 

  • Ling H, Roux E, Hempel D, Tao J, Smith M, Lonning S, Zuk A, Arbeeny C, Ledbetter S (2013) Transforming growth factor beta neutralization ameliorates pre-existing hepatic fibrosis and reduces cholangiocarcinoma in thioacetamide-treated rats. PLoS One 8(1):e54499

    Article  CAS  Google Scholar 

  • Londono R, Dziki JL, Haljasmaa E, Turner NJ, Leifer CA, Badylak SF (2017) The effect of cell debris within biologic scaffolds upon the macrophage response. J Biomed Mater Res A 105:2109

    Article  CAS  Google Scholar 

  • Maloney WJ, James RE, Smith RL (1996) Human macrophage response to retrieved titanium alloy particles in vitro. Clin Orthop Relat Res 322:268–278

    Article  Google Scholar 

  • Martinez FO, Helming L, Gordon S (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27(1):451–483

    Article  CAS  Google Scholar 

  • McWhorter FY, Wang T, Nguyen P, Chung T, Liu WF (2013) Modulation of macrophage phenotype by cell shape. Proc Natl Acad Sci U S A 110(43):17253–17258

    Article  CAS  Google Scholar 

  • Merkel KD, Erdmann JM, McHugh KP, Abu-Amer Y, Ross FP, Teitelbaum SL (1999) Tumor necrosis factor-alpha mediates orthopedic implant osteolysis. Am J Pathol 154(1):203–210

    Article  CAS  Google Scholar 

  • Moore LB, Sawyer AJ, Charokopos A, Skokos EA, Kyriakides TR (2015) Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces nfkappab activation in the foreign body response. Acta Biomater 11:37–47

    Article  CAS  Google Scholar 

  • Morris DL, Singer K, Lumeng CN (2011) Adipose tissue macrophages: phenotypic plasticity and diversity in lean and obese states. Curr Opin Clin Nutr Metab Care 14(4):341–346

    Article  Google Scholar 

  • Pajarinen J, Kouri VP, Jamsen E, Li TF, Mandelin J, Konttinen YT (2013) The response of macrophages to titanium particles is determined by macrophage polarization. Acta Biomater 9(11):9229–9240

    Article  CAS  Google Scholar 

  • Patil SD, Papadimitrakopoulos F, Burgess DJ (2004) Dexamethasone-loaded poly(lactic-co-glycolic) acid microspheres/poly(vinyl alcohol) hydrogel composite coatings for inflammation control. Diabetes Technol Ther 6(6):887–897

    Article  CAS  Google Scholar 

  • Pollice PF, Hsu J, Hicks DG, Bukata S, Rosier RN, Reynolds PR, Puzas JE, O’Keefe RJ (1998) Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway. J Orthop Res: Off Publ Orthop Res Soc 16(6):697–704

    Article  CAS  Google Scholar 

  • Quan H, Park HC, Kim Y, Yang HC (2017) Modulation of the anti-inflammatory effects of phosphatidylserine-containing liposomes by pegylation. J Biomed Mater Res A 105(5):1479–1486

    Article  CAS  Google Scholar 

  • Raghu G, Selman M (2015) Nintedanib and pirfenidone. New antifibrotic treatments indicated for idiopathic pulmonary fibrosis offer hopes and raises questions. Am J Respir Crit Care Med 191(3):252–254

    Article  CAS  Google Scholar 

  • Rao AJ, Gibon E, Ma T, Yao Z, Smith RL, Goodman SB (2012) Revision joint replacement, wear particles, and macrophage polarization. Acta Biomater 8(7):2815–2823

    Article  CAS  Google Scholar 

  • Rao AJ, Nich C, Dhulipala LS, Gibon E, Valladares R, Zwingenberger S, Smith RL, Goodman SB (2013) Local effect of il-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. J Biomed Mater Res A 101((7):1926–1934

    Article  Google Scholar 

  • Ren P-G, Irani A, Huang Z, Ma T, Biswal S, Goodman SB (2011) Continuous infusion of uhmwpe particles induces increased bone macrophages and osteolysis. Clin Orthop Relat Res 469(1):113–122

    Article  Google Scholar 

  • Roch T, Akymenko O, Kruger A, Jung F, Ma N, Lendlein A (2014) Expression pattern analysis and activity determination of matrix metalloproteinase derived from human macrophage subsets. Clin Hemorheol Microcirc 58(1):147–158

    PubMed  Google Scholar 

  • Rujitanaroj PO, Jao B, Yang J, Wang F, Anderson JM, Wang J, Chew SY (2013) Controlling fibrous capsule formation through long-term down-regulation of collagen type I (COL1A1) expression by nanofiber-mediated siRNA gene silencing. Acta Biomater 9(1):4513–4524

    Article  CAS  Google Scholar 

  • Schoenenberger AD, Schipanski A, Malheiro V, Kucki M, Snedeker JG, Wick P, Maniura-Weber K (2016) Macrophage polarization by titanium dioxide (tio2) particles: size matters. ACS Biomater Sci Eng 2(6):908–919

    Article  CAS  Google Scholar 

  • Spiller KL, Nassiri S, Witherel CE, Anfang RR, Ng J, Nakazawa KR, Yu T, Vunjak-Novakovic G (2015) Sequential delivery of immunomodulatory cytokines to facilitate the m1-to-m2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37:194–207

    Article  CAS  Google Scholar 

  • Takahashi H, Wang Y, Grainger DW (2010) Device-based local delivery of sirna against mammalian target of rapamycin (mtor) in a murine subcutaneous implant model to inhibit fibrous encapsulation. J Control Release 147(3):400–407

    Article  CAS  Google Scholar 

  • Trindade MC, Nakashima Y, Lind M, Sun DH, Goodman SB, Maloney WJ, Schurman DJ, Smith RL (1999) Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro. J Orthop Res Off Publ Orthop Res Soc 17(6):797–802

    Article  CAS  Google Scholar 

  • Trindade MC, Lind M, Nakashima Y, Sun D, Goodman SB, Schurman DJ, Smith RL (2001) Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha release by human monocyte/macrophages in vitro. Biomaterials 22(15):2067–2073

    Article  CAS  Google Scholar 

  • Valentin JE, Stewart-Akers AM, Gilbert TW, Badylak SF (2009) Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng Part A 15(7):1687–1694

    Article  CAS  Google Scholar 

  • Wang Y, Papadimitrakopoulos F, Burgess DJ (2013a) Polymeric “smart” coatings to prevent foreign body response to implantable biosensors. J Control Release 169(3):341–347

    Article  CAS  Google Scholar 

  • Wang Y, Wu NN, Mou YQ, Chen L, Deng ZL (2013b) Inhibitory effects of recombinant il-4 and recombinant il-13 on uhmwpe-induced bone destruction in the murine air pouch model. J Surg Res 180(2):e73–e81

    Article  CAS  Google Scholar 

  • Willert HG, Semlitsch M (1977) Reactions of the articular capsule to wear products of artificial joint prostheses. J Biomed Mater Res 11(2):157–164

    Article  CAS  Google Scholar 

  • Wimhurst JA, Brooks RA, Rushton N (2001) Inflammatory responses of human primary macrophages to particulate bone cements in vitro. J Bone Joint Surg 83(2):278–282

    Article  CAS  Google Scholar 

  • Yanagita M (2012) Inhibitors/antagonists of tgf-beta system in kidney fibrosis. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Ren Assoc 27(10):3686–3691

    CAS  Google Scholar 

  • Yoshizawa H, Morishita Y, Watanabe M, Ishibashi K, Muto S, Kusano E, Nagata D (2015) Tgf-beta(1)-sirna delivery with nanoparticles inhibits peritoneal fibrosis. Gene Ther 22(4):333–340

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dental Biomaterials Science and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea

    Hyeong-Cheol Yang, Hee Chul Park, Hongxuan Quan & Yongjoon Kim

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  1. Hyeong-Cheol Yang
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  2. Hee Chul Park
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  3. Hongxuan Quan
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  4. Yongjoon Kim
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Correspondence to Hyeong-Cheol Yang .

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  1. Seoul National University, Seoul, Korea (Republic of)

    Insup Noh

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Yang, HC., Park, H.C., Quan, H., Kim, Y. (2018). Immunomodulation of Biomaterials by Controlling Macrophage Polarization. In: Noh, I. (eds) Biomimetic Medical Materials. Advances in Experimental Medicine and Biology, vol 1064. Springer, Singapore. https://doi.org/10.1007/978-981-13-0445-3_12

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