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Cited by 43Bone Tissue Engineering MaterialsTissue Engineering and Regenerative MedicineWound Healing and Treatments

Extracellular Matrices to Modulate the Innate Immune Response and Enhance Bone Healing

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García-García, Andrés, Martin, Ivan·2019·Frontiers in Immunology
DOI 10.3389/fimmu.2019.02256PMC PMC6764079
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Abstract

Extracellular matrices (ECMs) have emerged as promising off-the-shelf products to induce bone regeneration, with the capacity not only to activate osteoprogenitors, but also to influence the immune response. ECMs generated starting from living cells such as mesenchymal stromal cells (MSCs) have the potential to combine advantages of native tissue-derived ECMs (e.g., physiological presentation of multiple regulatory factors) with those of synthetic ECMs (e.g., customization and reproducibility of composition). MSC-derived ECMs could be tailored by enrichment not only in osteogenic cytokines, but also in immunomodulatory factors, to skew the innate immune response toward regenerative processes. After reviewing the different immunoregulatory properties of ECM components, here we propose different approaches to engineer ECMs enriched in factors capable to regulate macrophage polarization, recruit host immune and mesenchymal cells, and stimulate the synthesis of other immunoinstructive cytokines. Finally, we offer a perspective on the possible evolution of the paradigm based on biological and chemico-physical design considerations, and the use of gene editing approaches.

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  • Increase in production of pro-inflammatory cytokines induces a shift in macrophage polarization toward the M1 phenotype, which is a critical determinant of grafts' long-term prognosis.

    “The increase in the production of pro-inflammatory cytokines also induces a shift in the polarization of macrophages as the critical determinant of grafts’ long-term prognosis toward the M1 phenotype [41, 42].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [41]

    The ‘Innate Immune System in Bone Repair’ section says the inflammatory response after bone injury initially polarizes macrophages toward M1, and that the M1-to-M2 transition favors bone regeneration. It does not establish that increased production of pro-inflammatory cytokines specifically causes the M1 shift or that this shift is a critical determinant of grafts’ long-term prognosis; it also notes that graft outcomes depend on other variables. No page numbers are available in our copy. (LLM, conf=0.84)

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  1. [1]Shrivats AR McDermott MC Hollinger JO. Bone tissue engineering: state of the union. Drug Discov Today. (2014) 19: 781– 6. 10.1016/j.drudis.2014.04.010 24768619 · DOI
  2. [2]Laurencin CT Ambrosio AM Borden MD Cooper JA Jr. Tissue engineering: orthopedic applications. Annu Rev Biomed Eng. (1999) 1: 19– 46. 10.1146/annurev.bioeng.1.1.19 11701481 · DOI
  3. [3]Mansour A Mezour MA Badran Z Tamimi F. (*) Extracellular matrices for bone regeneration: a literature review. Tissue Eng Part A. (2017) 23: 1436– 51. 10.1089/ten.tea.2017.0026 28562183 · DOI
  4. [4]Benders KE van Weeren PR Badylak SF Saris DB Dhert WJ Malda J Extracellular matrix scaffolds for cartilage and bone regeneration. Trends Biotechnol. (2013) 3: 169– 76. 10.1016/j.tibtech.2012.12.004 23298610 · DOI
  5. [5]Midwood KS Williams LV Schwarzbauer JE. Tissue repair and the dynamics of the extracellular matrix. Int.J.Biochem.Cell Biol. (2004) 36: 1031– 7. 10.1016/j.biocel.2003.12.003 15094118 · DOI · Paper page
  6. [6]Vaday GG Lider O. Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J.Leukoc.Biol. (2000) 67: 149– 59. 10.1002/jlb.67.2.149 10670574 · DOI
  7. [7]Aamodt JM Grainger DW. Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials. (2016) 86: 68– 82. 10.1016/j.biomaterials.2016.02.003 26890039 PMC4785021 · DOI · Paper page
  8. [8]Lutolf MP Weber FE Schmoekel HG Schense JC Kohler T Muller R. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat.Biotechnol. (2003) 21: 513– 18. 10.1038/nbt818 12704396 · DOI · Paper page
  9. [9]Sadr N Pippenger BE Scherberich A Wendt D Mantero S Martin I. Enhancing the biological performance of synthetic polymeric materials by decoration with engineered, decellularized extracellular matrix. Biomaterials. (2012) 33: 5085– 93. 10.1016/j.biomaterials.2012.03.082 22510434 · DOI
  10. [10]Clough BH McCarley MR Krause U Zeitouni S Froese JJ McNeill EP. Bone regeneration with osteogenically enhanced mesenchymal stem cells and their extracellular matrix proteins. J.Bone Miner.Res. (2015) 30: 83– 94. 10.1002/jbmr.2320 25130615 PMC4280327 · DOI
  11. [11]Bourgine PE Gaudiello E Pippenger B Jaquiery C Klein T Pigeot S Engineered extracellular matrices as biomaterials of tunable composition and function. Adv Funct Mater. (2017) 27: 1605486 10.1002/adfm.201605486 · DOI
  12. [12]Papadimitropoulos A Scotti C Bourgine P Scherberich A Martin I. Engineered decellularized matrices to instruct bone regeneration processes. Bone. (2015) 70: 66– 72. 10.1016/j.bone.2014.09.007 25260931 · DOI
  13. [13]Bourgine PE Scotti C Pigeot S Tchang LA Todorov A Martin I. Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis. Proc.Natl.Acad.Sci.USA. (2014) 111: 17426– 31. 10.1073/pnas.1411975111 25422415 PMC4267331 · DOI
  14. [15]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: 6692– 709. 10.1016/j.biomaterials.2011.05.078 21715002 · DOI · Paper page
  15. [16]Londono R Badylak SF. Biologic scaffolds for regenerative medicine: mechanisms of in vivo remodeling. Ann.Biomed.Eng. (2015) 43: 577– 92. 10.1007/s10439-014-1103-8 25213186 · DOI
  16. [17]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: 873– 84. 10.1002/jcb.10435 12616527 · DOI
  17. [18]Gorbet MB Sefton MV. Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. Biomaterials. (2004) 25: 5681– 703. 10.1016/j.biomaterials.2004.01.023 15147815 · DOI · Paper page
  18. [19]Johne J Blume C Benz PM Pozgajova M Ullrich M Schuh K. Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma. Biol.Chem. (2006) 387: 173– 8. 10.1515/BC.2006.023 16497149 · DOI
  19. [20]Baht GS Vi L Alman BA. The role of the immune cells in fracture healing. Curr Osteoporos Rep. (2018) 16: 138– 45. 10.1007/s11914-018-0423-2 29508143 PMC5866272 · DOI · Paper page
  20. [21]Bastian OW Koenderman L Alblas J Leenen LP Blokhuis TJ. Neutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury. Clin Immunol. (2016) 164: 78– 84. 10.1016/j.clim.2016.02.001 26854617 · DOI
  21. [22]Chang MK Raggatt LJ Alexander KA Kuliwaba JS Fazzalari NL Schroder K. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol. (2008) 181: 1232– 44. 10.4049/jimmunol.181.2.1232 18606677 · DOI
  22. [23]Mosser DM Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. (2008) 8: 958– 69. 10.1038/nri2448 19029990 PMC2724991 · DOI · Paper page
  23. [24]Schlundt C El KT Serra A Dienelt A Wendler S Schell H. Macrophages in bone fracture healing: their essential role in endochondral ossification. Bone. (2018) 106: 78– 89. 10.1016/j.bone.2015.10.019 26529389 · DOI
  24. [25]Einhorn TA The cell and molecular biology of fracture healing. Clin Orthop Relat Res. (1998) 55: S7– 21. 10.1097/00003086-199810001-00003 9917622 · DOI
  25. [26]Wang M Yuan Q Xie L. Mesenchymal stem cell-based immunomodulation: properties and clinical application. Stem Cells Int. (2018) 2018: 3057624. 10.1155/2018/3057624 30013600 PMC6022321 · DOI
  26. [27]Pajarinen J Lin T Gibon E Kohno Y Maruyama M Nathan K. Mesenchymal stem cell-macrophage crosstalk and bone healing, Biomaterials. (2019) 196: 80– 9. 10.1016/j.biomaterials.2017.12.025 29329642 PMC6028312 · DOI
  27. [28]Gerstenfeld LC Cho TJ Kon T Aizawa T Cruceta J Graves BD. Impaired intramembranous bone formation during bone repair in the absence of tumor necrosis factor-alpha signaling. Cells Tissues Organs. (2001) 169: 285– 94. 10.1159/000047893 11455125 · DOI
  28. [29]Mumme M Scotti C Papadimitropoulos A Todorov A Hoffmann W Bocelli-Tyndall C. Interleukin-1beta modulates endochondral ossification by human adult bone marrow stromal cells. Eur Cell Mater. (2012) 24: 224– 36. 10.22203/eCM.v024a16 23007908 · DOI
  29. [30]Lange J Sapozhnikova A Lu C Hu D Li X Miclau T III. Action of IL-1beta during fracture healing. J Orthop Res. (2010) 28: 778– 84. 10.1002/jor.21061 20041490 PMC2858256 · DOI
  30. [31]Guihard P Danger Y Brounais B David E Brion R Delecrin J. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling, Stem Cells. (2012) 30: 762– 72. 10.1002/stem.1040 22267310 · DOI
  31. [33]Champagne CM Takebe J Offenbacher S Cooper LF. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone. (2002) 30: 26– 31. 10.1016/S8756-3282(01)00638-X 11792561 · DOI
  32. [34]Rao AJ Nich C Dhulipala LS Gibon E Valladares R Zwingenberger S. Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. J Biomed Mater Res A. (2013) 101: 1926– 34. 10.1002/jbm.a.34486 23225668 PMC4073780 · DOI
  33. [36]Weidenbusch M Anders HJ Tissue microenvironments define and get reinforced by macrophage phenotypes in homeostasis or during inflammation, repair and fibrosis. J Innate Immun. (2012) 4: 463– 77. 10.1159/000336717 22507825 PMC6741480 · DOI
  34. [37]Murray PJ Allen JE Biswas SK Fisher EA Gilroy DW Goerdt S. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. (2014) 41: 14– 20. 10.1016/j.immuni.2014.06.008 25035950 PMC4123412 · DOI · Paper page
  35. [38]Todorov A Scotti C Barbero A Scherberich A Papadimitropoulos A Martin I Monocytes seeded on engineered hypertrophic cartilage do not enhance endochondral ossification capacity. Tissue Eng Part A. (2017) 23: 708– 15. 10.1089/ten.tea.2016.0553 28338424 · DOI
  36. [39]Valentin JE Stewart-Akers AM Gilbert TW Badylak SF. Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng Part A. (2009) 15: 1687– 94. 10.1089/ten.tea.2008.0419 19125644 PMC2792102 · DOI · Paper page
  37. [40]Alvarez MM Liu JC Trujillo-de SG Cha BH Vishwakarma A Ghaemmaghami AM. Delivery strategies to control inflammatory response: modulating M1-M2 polarization in tissue engineering applications. J Control Release. (2016) 240: 349– 63. 10.1016/j.jconrel.2016.01.026 26778695 PMC4945478 · DOI
  38. [42]Slivka PF Dearth CL Keane TJ Meng FW Medberry CJ Riggio RT. Fractionation of an ECM hydrogel into structural and soluble components reveals distinctive roles in regulating macrophage behavior. Biomater Sci. (2014) 2: 1521– 34. 10.1039/C4BM00189C 26829566 · DOI
  39. [43]Gowen BB Borg TK Ghaffar A Mayer EP. Selective adhesion of macrophages to denatured forms of type I collagen is mediated by scavenger receptors. Matrix Biol. (2000) 19: 61– 71. 10.1016/S0945-053X(99)00052-9 10686426 · DOI
  40. [44]Veres SP Brennan-Pierce EP Lee JM. Macrophage-like U937 cells recognize collagen fibrils with strain-induced discrete plasticity damage. J Biomed Mater Res A. (2015) 103: 397– 408. 10.1002/jbm.a.35156 24616426 · DOI
  41. [45]Rayahin JE Buhrman JS Zhang Y Koh TJ Gemeinhart RA. High and low molecular weight hyaluronic acid differentially influence macrophage activation. ACS Biomater Sci Eng. (2015) 1: 481– 93. 10.1021/acsbiomaterials.5b00181 26280020 PMC4533115 · DOI
  42. [46]Levesque MC Haynes BF. TNFalpha and IL-4 regulation of hyaluronan binding to monocyte CD44 involves posttranslational modification of CD44. Cell Immunol. (1999) 193: 209– 18. 10.1006/cimm.1999.1456 10222064 · DOI
  43. [47]Collins LE Troeberg L. Heparan sulfate as a regulator of inflammation and immunity. J Leukoc Biol. (2019) 105: 81– 92. 10.1002/JLB.3RU0618-246R 30376187 · DOI
  44. [48]Clark RA. Fibrin and wound healing. Ann N Y Acad Sci. (2001) 936: 355– 67. 10.1111/j.1749-6632.2001.tb03522.x 11460492 · DOI
  45. [49]Ciano PS Colvin RB Dvorak AM McDonagh J Dvorak HF. Macrophage migration in fibrin gel matrices. Lab Invest. (1986) 54: 62– 70. 3941542
  46. [50]Hsieh JY Smith TD Meli VS Tran TN Botvinick EL Liu WF. Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen. Acta Biomater. (2017) 47: 14– 24. 10.1016/j.actbio.2016.09.024 27662809 PMC5426227 · DOI
  47. [51]Yakovlev S Medved L. Effect of fibrinogen, fibrin, and fibrin degradation products on transendothelial migration of leukocytes. Thromb Res. (2018) 162: 93– 100. 10.1016/j.thromres.2017.11.007 29175090 PMC5811407 · DOI
  48. [52]Robson SC Shephard EG Kirsch RE. Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta. IL-6 and plasminogen activator inhibitors from monocytes in vitro. Br J Haematol. (1994) 86: 322– 6. 10.1111/j.1365-2141.1994.tb04733.x 8199021 · DOI
  49. [53]Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. (2010) 10: 712– 23. 10.1038/nri2852 20865019 · DOI
  50. [54]Reing JE Zhang L Myers-Irvin J Cordero KE Freytes DO Heber-Katz E. Degradation products of extracellular matrix affect cell migration and proliferation. Tissue Eng Part A. (2009) 15: 605– 14. 10.1089/ten.tea.2007.0425 18652541 · DOI · Paper page
  51. [56]Keane TJ Londono R Turner NJ Badylak SF. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials. (2012) 33: 1771– 81. 10.1016/j.biomaterials.2011.10.054 22137126 · DOI · Paper page
  52. [57]Sadtler K Allen BW Estrellas K Housseau F Pardoll DM Elisseeff JH. The scaffold immune microenvironment: biomaterial-mediated immune polarization in traumatic and nontraumatic applications. Tissue Eng Part A. (2017) 23: 1044– 53. 10.1089/ten.tea.2016.0304 27736323 PMC6436021 · DOI
  53. [58]Martino MM Maruyama K Kuhn GA Satoh T Takeuchi O Muller R. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration. Nat.Commun. (2016) 7: 11051. 10.1038/ncomms11051 27001940 PMC4804175 · DOI
  54. [59]Spiller KL Nassiri S Witherel CE Anfang RR Ng J Nakazawa KR. 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. 10.1016/j.biomaterials.2014.10.017 25453950 PMC4312192 · DOI · Paper page
  55. [60]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. 10.1016/j.biomaterials.2016.10.019 27760399 PMC5121003 · DOI
  56. [61]Senior RM Gresham HD Griffin GL Brown EJ Chung AE. Entactin stimulates neutrophil adhesion and chemotaxis through interactions between its Arg-Gly-Asp (RGD) domain and the leukocyte response integrin. J Clin Invest. (1992) 90: 2251– 7. 10.1172/JCI116111 1469085 PMC443376 · DOI
  57. [62]Lynn AD Kyriakides TR Bryant SJ. Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels. J Biomed Mater Res A. (2010) 93: 941– 53. 10.1002/jbm.a.32595 19708075 · DOI · Paper page
  58. [63]Zaveri TD Lewis JS Dolgova NV Clare-Salzler MJ Keselowsky BG. Integrin-directed modulation of macrophage responses to biomaterials. Biomaterials. (2014) 35: 3504– 15. 10.1016/j.biomaterials.2014.01.007 24462356 PMC3970928 · DOI · Paper page
  59. [64]Kim YK Chu SH Hsieh JY Kamoku CM Tenner AJ Liu WF. Incorporation of a ligand peptide for immune inhibitory receptor LAIR-1 on biomaterial surfaces inhibits macrophage inflammatory responses. Adv Healthc Mater. (2017) 6: 1700707. 10.1002/adhm.201700707 29083540 PMC5792650 · DOI
  60. [65]Wang H Li X Tomin E Doty SB Lane JM Carney DH. Thrombin peptide (TP508) promotes fracture repair by up-regulating inflammatory mediators, early growth factors, and increasing angiogenesis. J Orthop Res. (2005) 23: 671– 9. 10.1016/j.orthres.2004.10.002 15885490 · DOI
  61. [66]Santos SG Lamghari M Almeida CR Oliveira MI Neves N Ribeiro AC. Adsorbed fibrinogen leads to improved bone regeneration and correlates with differences in the systemic immune response. Acta Biomater. (2013) 9: 7209– 17. 10.1016/j.actbio.2013.04.008 23571000 · DOI
  62. [67]Vasconcelos DM Goncalves RM Almeida CR Pereira IO Oliveira MI Neves N. Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone regeneration. Biomaterials. (2016) 111: 163– 78. 10.1016/j.biomaterials.2016.10.004 27728815 · DOI
  63. [68]Paralkar VM Borovecki F Ke HZ Cameron KO Lefker B Grasser WA. An EP2 receptor-selective prostaglandin E2 agonist induces bone healing. Proc Natl Acad Sci USA. (2003) 100: 6736– 40. 10.1073/pnas.1037343100 12748385 PMC164516 · DOI
  64. [69]Tanaka M Sakai A Uchida S Tanaka S Nagashima M Katayama T. Prostaglandin E2 receptor (EP4) selective agonist (ONO-4819.CD) accelerates bone repair of femoral cortex after drill-hole injury associated with local upregulation of bone turnover in mature rats. Bone. (2004) 34: 940– 8. 10.1016/j.bone.2004.01.002 15193540 · DOI · Paper page
  65. [70]Toyoda H Terai H Sasaoka R Oda K Takaoka K. Augmentation of bone morphogenetic protein-induced bone mass by local delivery of a prostaglandin E EP4 receptor agonist. Bone. (2005) 37: 555– 62. 10.1016/j.bone.2005.04.042 16027058 · DOI
  66. [71]Jiang K Weaver JD Li Y Chen X Liang J Stabler CL. Local release of dexamethasone from macroporous scaffolds accelerates islet transplant engraftment by promotion of anti-inflammatory M2 macrophages. Biomaterials. (2017) 114: 71– 81. 10.1016/j.biomaterials.2016.11.004 27846404 · DOI
  67. [72]Patil SD Papadmitrakopoulos F Burgess DJ. Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. J Control Release. (2007) 117: 68– 79. 10.1016/j.jconrel.2006.10.013 17169457 · DOI · Paper page
  68. [73]Santo VE Gomes ME Mano JF Reis RL. Controlled release strategies for bone, cartilage, and osteochondral engineering–part I: recapitulation of native tissue healing and variables for the design of delivery systems. Tissue Eng Part B Rev. (2013) 19: 308– 26. 10.1089/ten.teb.2012.0138 23268651 PMC3690094 · DOI
  69. [74]Santo VE Gomes ME Mano JF Reis RL. Controlled release strategies for bone, cartilage, and osteochondral engineering–part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng Part B Rev. (2013) 19: 327– 52. 10.1089/ten.teb.2012.0727 23249320 PMC3690093 · DOI
  70. [75]Vo TN Kasper FK Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv Drug Deliv Rev. (2012) 64: 1292– 309. 10.1016/j.addr.2012.01.016 22342771 PMC3358582 · DOI
  71. [76]Yang SS Jin LH Park SH Kim MS Kim YJ Choi BH. Extracellular Matrix (ECM) multilayer membrane as a sustained releasing growth factor delivery system for rhTGF-beta3 in articular cartilage repair. PLoS.ONE. (2016) 11: e0156292. 10.1371/journal.pone.0156292 27258120 PMC4892547 · DOI
  72. [77]Lee SC Kwon IK Park K. Hydrogels for delivery of bioactive agents: a historical perspective. Adv Drug Deliv Rev. (2013) 65: 17– 20. 10.1016/j.addr.2012.07.015 22906864 PMC3514585 · DOI
  73. [78]Lienemann PS Lutolf MP Ehrbar M. Biomimetic hydrogels for controlled biomolecule delivery to augment bone regeneration. Adv Drug Deliv Rev. (2012) 64: 1078– 89. 10.1016/j.addr.2012.03.010 22465487 · DOI
  74. [79]Kim YH Furuya H Tabata Y. Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels. Biomaterials. (2014) 35: 214– 24. 10.1016/j.biomaterials.2013.09.103 24125774 · DOI
  75. [80]Kajahn J Franz S Rueckert E Forstreuter I Hintze V Moeller S. Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation. Biomatter. (2012) 2: 226– 36. 10.4161/biom.22855 23507888 PMC3568108 · DOI
  76. [81]Wang M Yu Y Dai K Ma Z Liu Y Wang J. Improved osteogenesis and angiogenesis of magnesium-doped calcium phosphate cement via macrophage immunomodulation. Biomater Sci. (2016) 4: 1574– 83. 10.1039/C6BM00290K 27709132 · DOI
  77. [82]Lam J Segura T. The modulation of MSC integrin expression by RGD presentation. Biomaterials. (2013) 34: 3938– 47. 10.1016/j.biomaterials.2013.01.091 23465825 PMC3650837 · DOI
  78. [83]Lo SC Tasso R Harnessing endogenous cellular mechanisms for bone repair. Front Bioeng Biotechnol. (2017) 5: 52 10.3389/fbioe.2017.00052 28929099 PMC5591576 · DOI
  79. [84]Julier Z Park AJ Briquez PS Martino MM. Promoting tissue regeneration by modulating the immune system. Acta Biomater. (2017) 53: 13– 28. 10.1016/j.actbio.2017.01.056 28119112 · DOI · Paper page
  80. [85]Hallmann R Zhang X Di RJ Li L Song J Hannocks MJ. The regulation of immune cell trafficking by the extracellular matrix. Curr Opin Cell Biol. (2015) 36: 54– 61. 10.1016/j.ceb.2015.06.006 26189064 · DOI
  81. [86]Andorko JI Jewell CM. Designing biomaterials with immunomodulatory properties for tissue engineering and regenerative medicine. Bioeng Transl Med. (2017) 2: 139– 55. 10.1002/btm2.10063 28932817 PMC5579731 · DOI
  82. [87]Hu Z Ma C Rong X Zou S Liu X. Immunomodulatory ECM-like microspheres for accelerated bone regeneration in diabetes mellitus. ACS Appl Mater Interfaces. (2018) 10: 2377– 90. 10.1021/acsami.7b18458 29280610 PMC6437671 · DOI
  83. [88]Huang YC Kaigler D Rice KG Krebsbach PH Mooney DJ. Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration. J Bone Miner Res. (2005) 20: 848– 57. 10.1359/JBMR.041226 15824858 · DOI
  84. [89]Lieberman JR Le LQ Wu L Finerman GA Berk A Witte ON. Regional gene therapy with a BMP-2-producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents. J Orthop Res. (1998) 16: 330– 9. 10.1002/jor.1100160309 9671928 · DOI
  85. [90]Blum JS Barry MA Mikos AG Jansen JA. In vivo evaluation of gene therapy vectors in ex vivo-derived marrow stromal cells for bone regeneration in a rat critical-size calvarial defect model. Hum Gene Ther. (2003) 14: 1689– 701. 10.1089/104303403322611719 14670121 · DOI
  86. [91]Tu Q Valverde P Chen J. Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells. Biochem Biophys Res Commun. (2006) 341: 1257– 65. 10.1016/j.bbrc.2006.01.092 16466699 PMC2831616 · DOI
  87. [92]Wu L Wu Y Lin Y Jing W Nie X Qiao J. Osteogenic differentiation of adipose derived stem cells promoted by overexpression of osterix. Mol Cell Biochem. (2007) 301: 83– 92. 10.1007/s11010-006-9399-9 17206379 · DOI
  88. [93]Jabbarzadeh E Starnes T Khan YM Jiang T Wirtel AJ Deng M. Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach. Proc Natl Acad Sci USA. (2008) 105: 11099– 104. 10.1073/pnas.0800069105 18678895 PMC2516212 · DOI
  89. [94]Vitale G Dicitore A Gentilini D Cavagnini F. Immunomodulatory effects of VEGF: clinical implications of VEGF-targeted therapy in human cancer. Cancer Biol Ther. (2010) 9: 694– 8. 10.4161/cbt.9.9.11691 20339315 · DOI
  90. [95]Sefcik LS Petrie Aronin CE Wieghaus KA Botchwey EA. Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering. Biomaterials. (2008) 29: 2869– 77. 10.1016/j.biomaterials.2008.03.017 18405965 PMC2711780 · DOI
  91. [96]Bryan AM Del PM. Sphingosine-1-phosphate receptors and innate immunity. Cell Microbiol. (2018) 20: e12836. 10.1111/cmi.12836 29498184 PMC5893408 · DOI
  92. [97]Choi JJ Yoo SA Park SJ Kang YJ Kim WU Oh IH. Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice. Clin Exp Immunol. (2008) 153: 269– 76. 10.1111/j.1365-2249.2008.03683.x 18713142 PMC2492894 · DOI
  93. [98]Lin T Pajarinen J Nabeshima A Lu L Nathan K Yao Z. Establishment of NF-kappaB sensing and interleukin-4 secreting mesenchymal stromal cells as an “on-demand” drug delivery system to modulate inflammation. Cytotherapy. (2017) 19: 1025– 34. 10.1016/j.jcyt.2017.06.008 28739167 PMC5563472 · DOI
  94. [99]Ramamoorth M Narvekar A. Non viral vectors in gene therapy- an overview. J Clin Diagn Res. (2015) 9: GE01– 6. 10.7860/JCDR/2015/10443.5394 25738007 PMC4347098 · DOI

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García-García, A., & Martin, I.
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2019-09-20
Volume
10
Pages
2256-2256
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2019.02256
PMC
PMC6764079
OpenAlex
W2972182118
Cited by
43
References
5
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 4
FWCI
0.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030-133110)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
extracellular matrix, bone regeneration, innate immune response, mesenchymal stem cells, macrophage polarization, immunomodulation, cell recruitment, genome editing, biomaterials engineering
MeSH terms
Animals, Bone Regeneration, Extracellular Matrix, Humans, Immunity, Innate, Osteogenesis, Cytokines, Mesenchymal Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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