The effect of the osteoimmunomodulatory mechanism on implant osseointegration and bone biomaterials induced bone regeneration

doi:10.12016/j.issn.2096-1456.2018.10.001

Abstract

Abstract:

With the development of implant dentistry and biomaterials, dental implants have become the first rehabilitative option proposed for the treatment of missing teeth. Most studies about dental implants and biomaterials currently focus on osteogenesis and the osseointegration of the implant, neglecting the importance of the immune response. In recent years, the development of osteoimmunology has been one of the greatest achievements in bone biomaterials; osteoimmunology has revealed the vital role of immune cells in regulating bone dynamics, implying the value of studies on materials with favorable osteoimmunomodulatory properties. This article reviews the integration between bone tissue and implants and summarizes the effects of the immune response during osseointegration and new bone formation to show the importance of regulating the immune response in this process. The effect of macrophages on osteogenesis and osteoclastogenesis is then reviewed due to the high plasticity and multiple roles of macrophages during this process. Accordingly, the interaction between the implants, the immune systems and the skeletal system is explained, showing the potential value of osteoimmunomodulation as a biological principle for developing bone biomaterials and new types of implants.

Key words: Bone immune regulation mechanism, Dental implants, Implant, Bone biomaterial, Bone formation, Inflammation, Surface modification

摘要：

随着口腔种植技术和骨生物材料的发展,种植牙已成为牙列缺损和牙列缺失的首选方案。围绕种植体和骨生物材料的研究主要集中于种植体骨结合和诱导成骨方面,而忽视了免疫反应在这一过程中的重要作用。近年来在骨生物材料领域,骨免疫学研究取得了巨大的成就,其揭示了免疫细胞在调节骨骼动力学方面的重要作用,展现了骨生物材料免疫调节性能方面的远大研究应用前景。本文首先回顾了种植体的骨结合机制,并着眼于免疫反应在骨结合和新骨形成过程中的重要作用从而展现了调节免疫反应在这一过程中的重要性。同时基于巨噬细胞高度的可塑性及其在免疫反应中的多重作用,着重探讨巨噬细胞对成骨、破骨细胞生成过程的重要影响。由此解释了种植体和骨生物材料、免疫系统及骨骼系统间的相互作用,阐明了骨免疫调节机制在新型种植体、骨生物材料设计和开发中存在的潜在价值。

关键词: 骨免疫调节机制, 口腔种植, 种植体, 骨生物材料, 骨形成, 骨结合, 炎症, 表面改性

CLC Number:

R782.1

Jiang CHEN,Xuxi CHEN,Lin ZHOU. The effect of the osteoimmunomodulatory mechanism on implant osseointegration and bone biomaterials induced bone regeneration[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(10): 613-620.

陈江,陈旭晞,周麟. 骨免疫调节机制对种植体骨结合及骨生物材料引导骨再生的影响[J]. 口腔疾病防治, 2018, 26(10): 613-620.

References 66

[1]	Brown BN, Badylak SF . Expanded applications, shifting paradigms and an improved understanding of host-biomaterial interactions[J]. Acta Biomater, 2013,9(2):4948-4955.
[2]	Franz S, Rammelt S, Scharnweber D , et al. Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials[J]. Biomaterials, 2011,32(28):6692-6709. DOI
[3]	Kobayashi SD, Voyich JM, Burlak C , et al. Neutrophils in the innate immune response[J]. Arch Immunol Ther Exp (Warsz), 2005,53(6):505-517.
[4]	Anderson JM, Rodriguez A, Chang DT . Foreign body reaction to biomaterials[J]. Semin Immunol, 2008,20(2):86-100. DOI URL PMID
[5]	Tang L, Jennings TA, Eaton JW . Mast cells mediate acute inflammatory responses to implanted biomaterials[J]. Proc Natl Acad Sci U S A, 1998,95(15):8841-8846. DOI URL PMID
[6]	樊牮, 邹耿森, 陈江 . 钛种植体表面纳米改性及其与机体免疫应答[J]. 国际口腔医学杂志, 2014,41(6):691-693. DOI URL
[7]	Hart PH, Bonder CS, Balogh J , et al. Differential responses of human monocytes and macrophages to IL-4 and IL-13[J]. J Leukoc Biol, 1999,66(4):575-578. DOI URL PMID
[8]	Chen Z, Wu C, Yuen J , et al. Influence of osteocytes in the in vitro and in vivo β-tricalcium phosphate-stimulated osteogenesis[J]. J Biomed Mater Res A, 2014,102(8):2813-2823.
[9]	Ma M, Liu WF, Hill PS , et al. Development of cationic polymer coatings to regulate foreign-body responses[J]. Adv Mater, 2011,23(24):H189-H194. DOI
[10]	Hess K, Ushmorov A, Fiedler J , et al. TNFalpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappaB signaling pathway[J]. Bone, 2009,45(2):367-376. DOI
[11]	Guihard P, Boutet MA , Brounais-Le Royer B , et al.Oncostatin m, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury[J]. Am J Pathol, 2015,185(3):765-775.
[12]	Gilbert L, He X, Farmer P , et al. Inhibition of osteoblast differentiation by tumor necrosis factor-α[J]. Endocrinology, 2000,141(11):3956-3964. DOI URL PMID
[13]	Feldmann M, Maini RN . Anti-TNF therapy, from rationale to standard of care: what lessons has it taught us[J]. J Immunol, 2010,185(2):791-794. DOI URL PMID
[14]	Liu Y, Wang L, Kikuiri T , et al. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α[J]. Nat Med, 2011,17(12):1594-1601.
[15]	Chang J, Liu F, Lee M , et al. NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation[J]. Proc Natl Acad Sci U S A, 2013,110(23):9469-9474.
[16]	Yamashita M, Otsuka F, Mukai T , et al. Simvastatin inhibits osteoclast differentiation induced by bone morphogenetic protein-2 and RANKL through regulating MAPK, AKT and Src signaling[J]. Regul Pept, 2010,162(1-3):99-108.
[17]	Arron JR, Choi Y . Osteoimmunology - bone versus immune system[J]. Nature, 2000,408(6812):535-536. DOI URL
[18]	Zaidi M . Skeletal remodeling in health and disease[J]. Nat Med, 2007,13(7):791-801.
[19]	Meguid MH, Hamad YH, Swilam RS , et al. Relation of interleukin-6 in rheumatoid arthritis patients to systemic bone loss and structural bone damage[J]. Rheumatol Int, 2013,33(3):697-703. DOI
[20]	Devlin RD, Reddy SV, Savino R , et al. IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1,25(OH)2D3, on osteoclast-like cell formation in normal human bone marrow cultures[J]. J Bone Miner Res, 1998,13(3):393-399.
[21]	Palmqvist P, Persson E, Conaway HH , et al. IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae[J]. J Immunol, 2002,169(6):3353-3362.
[22]	Sims NA, Quinn JM . Osteoimmunology: oncostatin M as a pleiotropic regulator of bone formation and resorption in health and disease[J]. Bonekey Rep, 2014,3:527.
[23]	Boyce BF, Xing LP . Biology of RANK, RANKL, and osteoprotegerin[J]. Arthritis Res Ther, 2007,9(Suppl 1):1. DOI URL PMID
[24]	Wright HL, Mccarthy HS, Middleton J , et al. RANK, RANKL and osteoprotegerin in bone biology and disease[J]. Curr Rev Musculoskelet Med, 2009,2(1):56-64. DOI URL PMID
[25]	Li Y, Toraldo G, Li A , et al. B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo[J]. Blood, 2007,109(9):3839-3848.
[26]	Pacifici R . The immune system and bone[J]. Arch Biochem Biophys, 2010,503(1):41-53. DOI URL PMID
[27]	Gordon S, Helming L, Estrada FOM . Alternative activation of macrophages: concepts and prospects[M] // Macrophages: Biology and Role in the Pathology of Diseases. Springer New York, 2014: 59-76.
[28]	Martinez FO, Gordon S . The M1 and M2 paradigm of macrophage activation: time for reassessment[J]. F1000Prime Rep, 2014,6:13. DOI URL PMID
[29]	Guihard P, Danger Y, Brounais B , et al. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling[J]. Stem Cells, 2012,30(4):762-772.
[30]	Malekshah AK, Moghaddam AE, Daraka SM . Comparison of conditioned medium and direct co-culture of human granulosa cells on mouse embryo development[J]. Indian J Exp Biol, 2006,44(3):189-192.
[31]	Spiller KL, Nassiri S, Witherel CE , et al. Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds[J]. Biomaterials, 2015,37:194-207.
[32]	Alfarsi MA, Hamlet SM, Ivanovski S . Titanium surface hydrophilicity modulates the human macrophage inflammatory cytokine response[J]. J Biomed Mater Res A, 2014,102(1):60-67. DOI URL PMID
[33]	Trindade R, Albrektsson T, Wennerberg A . Current concepts for the biological basis of dental implants: foreign body equilibrium and osseointegration dynamics[J]. Oral Maxillofac Surg Clin North Am, 2015,27(2):175-183.
[34]	Vasconcelos DP, Costa M, Amaral IF , et al. Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators[J]. Biomaterials, 2015,37:116-123.
[35]	Luo X, Barbieri D, Davison N , et al. Zinc in Calcium phosphate mediates bone induction: in vitro and in vivo model[J]. Acta Biomater, 2014,10(1):477-485. DOI URL PMID
[36]	Bouvet-Gerbettaz S, Boukhechba F, Balaguer T , et al. Adaptive immune response inhibits ectopic mature bone formation induced by BMSCs/BCP/plasma composite in immune-competent mice[J]. Tissue Eng Part A, 2014,20(21-22):2950-2962.
[37]	Gamblin AL, Brennan MA, Renaud A , et al. Bone tissue formation with human mesenchymal stem cells and biphasic Calcium phosphate ceramics: the local implication of osteoclasts and macrophages[J]. Biomaterials, 2014,35(36):9660-9667. DOI
[38]	Miron RJ, Zohdi H, Fujioka-Kobayashi M , et al. Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells[J]. Acta Biomater, 2016,46:15-28. DOI URL PMID
[39]	Dobrovolskaia MA, Mcneil SE . Immunological properties of engineered nanomaterials[J]. Nat Nanotechnol, 2007,2(8):469-478. DOI URL PMID
[40]	Weiss L . The cell periphery[J]. Int Rev Cytol, 1969,26(3789):63-105.
[41]	Chen X, Wang W, Cheng S , et al. Mimicking bone nanostructure by combining block copolymer self-assembly and 1D crystal nucleation[J]. ACS Nano, 2013,7(9):8251-8257.
[42]	Tsimbouri P, Gadegaard N, Burgess K , et al. Nanotopographical effects on mesenchymal stem cell morphology and phenotype[J]. J Cell Biochem, 2014,115(2):380-390. DOI URL PMID
[43]	Dang Y, Zhang L, Song W , et al. In vivo osseointegration of Ti implants with a strontium-containing nanotubular coating[J]. Int J Nanomedicine, 2016,11:1003-1011. DOI URL PMID
[44]	Smith BS, Capellato P, Kelley SA , et al. Reduced in vitro immune response on Titania nanotube arrays compared to Titanium surface[J]. Biomater Sci, 2013,1(3):322-332. DOI URL
[45]	Lü WL, Wang N, Gao P , et al. Effects of anodic Titanium dioxide nanotubes of different diameters on macrophage secretion and expression of cytokines and chemokines[J]. Cell Prolif, 2015,48(1):95-104.
[46]	Wilkinson A, Hewitt RN, Mcnamara LE , et al. Biomimetic microtopography to enhance osteogenesis in vitro[J]. Acta Biomater, 2011,7(7):2919-2925. DOI URL PMID
[47]	Davison MJ, Mcmurray RJ, Smith CA , et al. Nanopit-induced osteoprogenitor cell differentiation: the effect of nanopit depth[J]. J Tissue Eng, 2016,7:2041731416652778. DOI URL PMID
[48]	Zhang Y, Venugopal JR, El-Turki A , et al. Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering[J]. Biomaterials, 2008,29(32):4314-4322. DOI
[49]	Bartneck M, Heffels KH, Pan Y , et al. Inducing healing-like human primary macrophage phenotypes by 3D hydrogel coated nanofibres[J]. Biomaterials, 2012,33(16):4136-4146. DOI URL PMID
[50]	Wang K, Hou WD, Wang X , et al. Overcoming foreign-body reaction through nanotopography: biocompatibility and immunoisolation properties of a nanofibrous membrane[J]. Biomaterials, 2016,102:249-258.
[51]	Saino E, Focarete ML, Gualandi C , et al. Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines[J]. Biomacromolecules, 2011,12(5):1900-1911. DOI
[52]	Sjöström T, Mcnamara LE, Meek RM , et al. 2D and 3D nanopatterning of Titanium for enhancing osteoinduction of stem cells at implant surfaces[J]. Adv Healthc Mater, 2013,2(9):1285-1293.
[53]	Mohiuddin M, Pan HA, Hung YC , et al. Control of growth and inflammatory response of macrophages and foam cells with nanotopography[J]. Nanoscale Res Lett, 2012,7(1):394 . DOI URL PMID
[54]	Fujita S, Ohshima M, Iwata H . Time-lapse observation of cell alignment on nanogrooved patterns[J]. J R Soc Interface, 2009,6(Suppl 3):S269-S277. DOI URL PMID
[55]	Zhu B, Lu Q, Yin J , et al. Alignment of osteoblast-like cells and cell-produced collagen matrix induced by nanogrooves[J]. Tissue Eng, 2005,11(5/6):825-834. DOI URL PMID
[56]	Lamers E, Walboomers XF, Domanski M , et al. In vitro and in vivo evaluation of the inflammatory response to nanoscale grooved substrates[J]. Nanomedicine, 2012,8(3):308-317. DOI URL PMID
[57]	Pujari S, Hoess A, Shen J , et al. Effects of nanoporous alumina on inflammatory cell response[J]. J Biomed Mater Res A, 2014,102(11):3773-3780. DOI URL PMID
[58]	Chen Z, Ni S, Han S , et al. Nanoporous microstructures mediate osteogenesis by modulating the osteo-immune response of macrophages[J]. Nanoscale, 2017,9(2):706-718.
[59]	Chu CY, Deng J, Sun XC , et al. Collagen membrane and immune response in guided bone regeneration: recent progress and perspectives[J]. Tissue Eng Part B Rev, 2017,23(5):421-435.
[60]	Chu CY, Deng J, Hou Y , et al. Application of PEG and EGCG modified collagen-base membrane to promote osteoblasts proliferation[J]. Mater Sci Eng C Mater Biol Appl, 2017,76:31-36. DOI URL PMID
[61]	Ramazanoglu M, Lutz R, Ergun C , et al. The effect of combined delivery of recombinant human bone morphogenetic protein-2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium-phosphate-coated implants on osseointegration[J]. Clin Oral Implants Res, 2011,22(12):1433-1439.
[62]	Von Wilmowsky C, Moest T, Nkenke E , et al. Implants in bone: part I. A current overview about tissue response, surface modifications and future perspectives[J]. Oral Maxillofac Surg, 2014,18(3):243-257.
[63]	Shim DW, Heo KH, Kim YK , et al. Anti-Inflammatory action of an antimicrobial model peptide that suppresses the TRIF-Dependent signaling pathway via inhibition of Toll-Like receptor 4 endocytosis in Lipopolysaccharide-Stimulated macrophages[J]. PLoS One, 2015,10(5):e0126871.
[64]	Liu Y, Xia X, Xu L , et al. Design of hybrid β-hairpin peptides with enhanced cell specificity and potent anti-inflammatory activity[J]. Biomaterials, 2013,34(1):237-250. DOI
[65]	Veldhuizen EJ, Schneider VA, Agustiandari H , et al. Antimicrobial and immunomodulatory activities of PR-39 derived peptides[J]. PLoS One, 2014,9(4):e95939 DOI URL PMID
[66]	Zhou L, Lai Y, Huang W , et al. Biofunctionalization of microgroove Titanium surfaces with an antimicrobial peptide to enhance their bactericidal activity and cytocompatibility[J]. Colloids Surf B Biointerfaces, 2015,128:552-560.