Skip to main content
SpringerLink
Log in

Foreign Body Reaction to Subcutaneous Implants

  • Conference paper
Immune Responses to Biosurfaces

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 865))

Abstract

Subcutaneously implanted materials trigger the host’s innate immune system, resulting in the foreign body reaction. This reaction consists of protein adsorption on the implant surface, inflammatory cell infiltration, macrophage fusion into foreign body giant cells, fibroblast activation and ultimately fibrous encapsulation. This series of events may affect the function of subcutaneous implants, such as inhibition of drug diffusion from long-acting drug delivery depots and medical device failure. The foreign body reaction is a complex phenomenon and is not yet fully understood; ongoing research studies aim to elucidate the cellular and molecular dynamics involved. Recent studies have revealed information about the specific role of macrophages and their differential activation towards pro- and anti-inflammatory states, as well as species differences in the timing of collagen deposition and fibrosis. Understanding of the diverse processes involved in the foreign body reaction has led to multiple approaches towards its negation. Delivery of tissue response modifiers, such as corticosteroids, NSAIDs, antifibrotic agents, and siRNAs, has been used to prevent or minimize fibrosis. Of these, delivery of dexamethasone throughout the implantation period is the most common method to prevent inflammation and fibrosis. More recent approaches employ surface modifications to minimize protein adsorption to ‘ultra-low’ levels and reduce fibrosis. However, the diverse nature of the processes involved in the foreign body reaction favor the use of corticosteroids due to their wide spectrum action compared to other approaches. To date, combination approaches, such as hydrophilic coatings that reduce protein adsorption combined with delivery of dexamethasone are the most effective.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Silver IA. The mechanics of wound healing. Equine Vet J. 1979;11(2):93–6. PubMed.

    Article  CAS  PubMed  Google Scholar 

  2. Carrico TJ, Mehrhof Jr AI, Cohen IK. Biology of wound healing. Surg Clin North Am. 1984;64(4):721–33. PubMed.

    CAS  PubMed  Google Scholar 

  3. Hammerle CH, Giannobile WV, Working Group 1 of the European Workshop on P. Biology of soft tissue wound healing and regeneration--consensus report of Group 1 of the 10th European Workshop on Periodontology. J Clin Periodontol. 2014;41 Suppl 15:S1–5. PubMed.

    Article  PubMed  Google Scholar 

  4. Safferling K, Sutterlin T, Westphal K, Ernst C, Breuhahn K, James M, et al. Wound healing revised: a novel reepithelialization mechanism revealed by in vitro and in silico models. J Cell Biol. 2013;203(4):691–709. Pubmed Central PMCID: 3840932.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Namdari S, Melnic C, Huffman GR. Foreign body reaction to acellular dermal matrix allograft in biologic glenoid resurfacing. Clin Orthop Relat Res. 2013;471(8):2455–8. Pubmed Central PMCID: 3705065.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol. 2008;20(2):86–100. Pubmed Central PMCID: 2327202.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Morais JM, Papadimitrakopoulos F, Burgess DJ. Biomaterials/tissue interactions: possible solutions to overcome foreign body response. AAPS J. 2010;12(2):188–96. Pubmed Central PMCID: 2844517.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Kyriakides TR, Bornstein P. Matricellular proteins as modulators of wound healing and the foreign body response. Thromb Haemost. 2003;90(6):986–92. PubMed.

    CAS  PubMed  Google Scholar 

  9. Nomoto K. Mechanism of the response of the living body to foreign material. Allergy. 1990;39(5):437–41. PubMed.

    CAS  PubMed  Google Scholar 

  10. Zaveri TD, Lewis JS, Dolgova NV, Clare-Salzler MJ, Keselowsky BG. Integrin-directed modulation of macrophage responses to biomaterials. Biomaterials. 2014;35(11):3504–15. Pubmed Central PMCID: 3970928.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Cei S, Karapetsa D, Aleo E, Graziani F. Protein Adsorption on a Laser-Modified Titanium Implant Surface. Implant Dent. 2015;24(2):134–41. PubMed.

    PubMed  Google Scholar 

  12. Nune KC, Misra RD. Pre-adsorption of protein on electrochemically grooved nanostructured stainless steel implant and relationship to cellular activity. J Biomed Nanotechnol. 2014;10(7):1320–35. PubMed.

    Article  CAS  PubMed  Google Scholar 

  13. Wang LC, Chen XG, Xu QC, Liu CS, le Yu J, Zhou YM. Plasma protein adsorption pattern and tissue-implant reaction of poly (vinyl alcohol)/carboxymethyl-chitosan blend films. J Biomater Sci Polym Ed. 2008;19(1):113–29. PubMed.

    Article  CAS  PubMed  Google Scholar 

  14. Bagnall RD, Arundel PA. A method for the prediction of protein adsorption on implant surfaces. J Biomed Mater Res. 1983;17(3):459–66. PubMed.

    Article  CAS  PubMed  Google Scholar 

  15. Gifford R, Kehoe JJ, Barnes SL, Kornilayev BA, Alterman MA, Wilson GS. Protein interactions with subcutaneously implanted biosensors. Biomaterials. 2006;27(12):2587–98. PubMed.

    Article  CAS  PubMed  Google Scholar 

  16. 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. PubMed.

    Article  CAS  PubMed  Google Scholar 

  17. Feng XL, Yi CX, Zhang YM, Wang YM, Wang YR, Peng C, et al. Immunological effects of polyacrylamide hydrogel injection in human body. Zhonghua zheng xing wai ke za zhi. 2004;20(5):349–50. PubMed.

    PubMed  Google Scholar 

  18. Schmidt S, Haase G, Csomor E, Lutticken R, Peltroche-Llacsahuanga H. Inhibitor of complement, Compstatin, prevents polymer-mediated Mac-1 up-regulation of human neutrophils independent of biomaterial type tested. J Biomed Mater Res A. 2003;66(3):491–9. PubMed.

    Article  CAS  PubMed  Google Scholar 

  19. Yang J, Jao B, McNally AK, Anderson JM. In vivo quantitative and qualitative assessment of foreign body giant cell formation on biomaterials in mice deficient in natural killer lymphocyte subsets, mast cells, or the interleukin-4 receptoralpha and in severe combined immunodeficient mice. J Biomed Mater Res A. 2014;102(6):2017–23. PubMed.

    Article  PubMed  Google Scholar 

  20. Anderson JM, Defife K, McNally A, Collier T, Jenney C. Monocyte, macrophage and foreign body giant cell interactions with molecularly engineered surfaces. J Mater Sci Mater Med. 1999;10(10/11):579–88. PubMed.

    Article  CAS  PubMed  Google Scholar 

  21. Kao WJ, McNally AK, Hiltner A, Anderson JM. Role for interleukin-4 in foreign-body giant cell formation on a poly (etherurethane urea) in vivo. J Biomed Mater Res. 1995;29(10):1267–75. PubMed.

    Article  CAS  PubMed  Google Scholar 

  22. Smetana Jr K. Multinucleate foreign-body giant cell formation. Exp Mol Pathol. 1987;46(3):258–65. PubMed.

    Article  PubMed  Google Scholar 

  23. Brokopp CE, Schoenauer R, Richards P, Bauer S, Lohmann C, Emmert MY, et al. Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata. Eur Heart J. 2011;32(21):2713–22. Pubmed Central PMCID: 3205479.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Laato M, Kahari VM, Niinikoski J, Vuorio E. Epidermal growth factor increases collagen production in granulation tissue by stimulation of fibroblast proliferation and not by activation of procollagen genes. Biochem J. 1987;247(2):385–8. Pubmed Central PMCID: 1148420.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Virakul S, Dalm VA, Paridaens D, van den Bosch WA, Hirankarn N, van Hagen PM, et al. The tyrosine kinase inhibitor dasatinib effectively blocks PDGF-induced orbital fibroblast activation. Graefes Arch Clin Exp Ophthalmol. 2014;252(7):1101–9. PubMed.

    Article  CAS  PubMed  Google Scholar 

  26. van Steensel L, Hooijkaas H, Paridaens D, van den Bosch WA, Kuijpers RW, Drexhage HA, et al. PDGF enhances orbital fibroblast responses to TSHR stimulating autoantibodies in Graves’ ophthalmopathy patients. J Clin Endocrinol Metab. 2012;97(6):944–53. PubMed.

    Article  Google Scholar 

  27. Wang X, Waldeck H, Kao WJ. The effects of TGF-alpha, IL-1beta and PDGF on fibroblast adhesion to ECM-derived matrix and KGF gene expression. Biomaterials. 2010;31(9):2542–8. Pubmed Central PMCID: 2813970.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Lachapelle F, Avellana-Adalid V, Nait-Oumesmar B, Baron-Van EA. Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor AB (PDGF AB) promote adult SVZ-derived oligodendrogenesis in vivo. Mol Cell Neurosci. 2002;20(3):390–403. PubMed.

    Article  CAS  PubMed  Google Scholar 

  29. Kim WJ, Mohan RR, Mohan RR, Wilson SE. Effect of PDGF, IL-1alpha, and BMP2/4 on corneal fibroblast chemotaxis: expression of the platelet-derived growth factor system in the cornea. Invest Ophthalmol Vis Sci. 1999;40(7):1364–72. PubMed.

    CAS  PubMed  Google Scholar 

  30. Xu J, Clark RA. Extracellular matrix alters PDGF regulation of fibroblast integrins. J Cell Biol. 1996;132(1-2):239–49. Pubmed Central PMCID: 2120701.

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez A, Meyerson H, Anderson JM. Quantitative in vivo cytokine analysis at synthetic biomaterial implant sites. J Biomed Mater Res A. 2009;89(1):152–9. Pubmed Central PMCID: 3864694.

    PubMed  Google Scholar 

  32. Ward WK, Li AG, Siddiqui Y, Federiuk IF, Wang XJ. Increased expression of Interleukin-13 and connective tissue growth factor, and their potential roles during foreign body encapsulation of subcutaneous implants. J Biomater Sci Polym Ed. 2008;19(8):1065–72. PubMed.

    Article  CAS  PubMed  Google Scholar 

  33. von Grote EC, Venkatakrishnan V, Duo J, Stenken JA. Long-term subcutaneous microdialysis sampling and qRT-PCR of MCP-1, IL-6 and IL-10 in freely-moving rats. Mol BioSyst. 2011;7(1):150–61. Pubmed Central PMCID: 3864033.

    Article  Google Scholar 

  34. Castro PR, Marques SM, Viana CT, Campos PP, Ferreira MA, Barcelos LS, et al. Deletion of the chemokine receptor CCR2 attenuates foreign body reaction to implants in mice. Microvasc Res. 2014;95:37–45. PubMed.

    Article  CAS  PubMed  Google Scholar 

  35. Sawyer AJ, Tian W, Saucier-Sawyer JK, Rizk PJ, Saltzman WM, Bellamkonda RV, et al. The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation. Biomaterials. 2014;35(25):6698–706. Pubmed Central PMCID: 4128094.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Auquit-Auckbur I, Caillot F, Arnoult C, Menard JF, Drouot L, Courville P, et al. Role of toll-like receptor 4 in the inflammation reaction surrounding silicone prosthesis. Acta Biomater. 2011;7(5):2047–52. PubMed.

    Article  CAS  PubMed  Google Scholar 

  37. van Putten SM, Ploeger DT, Popa ER, Bank RA. Macrophage phenotypes in the collagen-induced foreign body reaction in rats. Acta Biomater. 2013;9(5):6502–10. PubMed.

    Article  PubMed  Google Scholar 

  38. Kastellorizios M, Papadimitrakopoulos F, Burgess DJ. Prevention of foreign body reaction in a pre-clinical large animal model. J Control Release. 2015;202:101–7. PubMed.

    Article  CAS  PubMed  Google Scholar 

  39. Wang Y, Papadimitrakopoulos F, Burgess DJ. Polymeric “smart” coatings to prevent foreign body response to implantable biosensors. J Control Release. 2013;169(3):341–7. PubMed.

    Google Scholar 

  40. Bhardwaj U, Sura R, Papadimitrakopoulos F, Burgess DJ. PLGA/PVA hydrogel composites for long-term inflammation control following s.c. implantation. Int J Pharm. 2010;384(1-2):78–86. PubMed.

    Article  CAS  PubMed  Google Scholar 

  41. Bhardwaj U, Sura R, Papadimitrakopoulos F, Burgess DJ. Controlling acute inflammation with fast releasing dexamethasone-PLGA microsphere/PVA hydrogel composites for implantable devices. J Diabetes Sci Technol. 2007;1(1):8–17. Pubmed Central PMCID: 2769608.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Bartsch I, Willbold E, Yarmolenko S, Witte F. In vivo fluorescence imaging of apoptosis during foreign body response. Biomaterials. 2012;33(29):6926–32. PubMed.

    Article  CAS  PubMed  Google Scholar 

  43. Hiromoto S, Inoue M, Taguchi T, Yamane M, Ohtsu N. In vitro and in vivo biocompatibility and corrosion behaviour of a bioabsorbable magnesium alloy coated with octacalcium phosphate and hydroxyapatite. Acta Biomater. 2015;11:520–30. PubMed.

    Article  CAS  PubMed  Google Scholar 

  44. Rajam AM, Jithendral P, Mandal AB, Rose C. Evaluation of in vitro macrophage response and in vivo host response to growth factors incorporated chitosan nanoparticle impregnated collagen-chitosan scaffold. J Biomed Nanotechnol. 2014;10(3):508–18. PubMed.

    Article  CAS  PubMed  Google Scholar 

  45. Blakney AK, Swartzlander MD, Bryant SJ. The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly (ethylene glycol)-based hydrogels. J Biomed Mater Res A. 2012;100(6):1375–86. Pubmed Central PMCID: 3339197.

    Article  PubMed Central  PubMed  Google Scholar 

  46. 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(3):941–53. PubMed.

    PubMed  Google Scholar 

  47. Sides CR, Stenken JA. Microdialysis sampling techniques applied to studies of the foreign body reaction. Eur J Pharm Sci. 2014;57:74–86. Pubmed Central PMCID: 4004681.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Keeler GD, Durdik JM, Stenken JA. Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue. Eur J Pharm Sci. 2014;57:60–7. Pubmed Central PMCID: 4004663.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Tsai YT, Zhou J, Weng H, Tang EN, Baker DW, Tang L. Optical imaging of fibrin deposition to elucidate participation of mast cells in foreign body responses. Biomaterials. 2014;35(7):2089–96. Pubmed Central PMCID: 3934503.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Wolf MT, Vodovotz Y, Tottey S, Brown BN, Badylak SF. Predicting In Vivo Responses to Biomaterials via Combined In Vitro and In Silico Analysis. Tissue Eng Part C Methods. 2015;21(2):148–59. PubMed.

    Article  CAS  PubMed  Google Scholar 

  51. McDonald SM, Matheson LA, McBane JE, Kuraitis D, Suuronen E, Santerre JP, et al. Use of monocyte/endothelial cell co-cultures (in vitro) and a subcutaneous implant mouse model (in vivo) to evaluate a degradable polar hydrophobic ionic polyurethane. J Cell Biochem. 2011;112(12):3762–72. PubMed.

    Article  CAS  PubMed  Google Scholar 

  52. Damanik FF, Rothuizen TC, van Blitterswijk C, Rotmans JI, Moroni L. Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix. Sci Rep. 2014;4:6325. Pubmed Central PMCID: 4168285.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Wisniewski N, Klitzman B, Miller B, Reichert WM. Decreased analyte transport through implanted membranes: differentiation of biofouling from tissue effects. J Biomed Mater Res. 2001;57(4):513–21. PubMed.

    Article  CAS  PubMed  Google Scholar 

  54. Voskerician G, Shive MS, Shawgo RS, von Recum H, Anderson JM, Cima MJ, et al. Biocompatibility and biofouling of MEMS drug delivery devices. Biomaterials. 2003;24(11):1959–67. PubMed.

    Article  CAS  PubMed  Google Scholar 

  55. Wang QS, Cui YL, Gao LN, Guo Y, Li RX, Zhang XZ. Reduction of the pro-inflammatory response by tetrandrine-loading poly (l-lactic acid) films in vitro and in vivo. J Biomed Mater Res A. 2014;102(11):4098–107. PubMed.

    Article  PubMed  Google Scholar 

  56. Ziyan L, Yongmei Z, Nan Z, Ning T, Baolin L. Evaluation of the anti-inflammatory activity of luteolin in experimental animal models. Planta Med. 2007;73(3):221–6. PubMed.

    Article  PubMed  Google Scholar 

  57. Suleyman H, Gul HI, Gul M, Alkan M, Gocer F. Anti-inflammatory activity of bis (3-aryl-3-oxo-propyl) methylamine hydrochloride in rat. Biol Pharm Bull. 2007;30(1):63–7. PubMed.

    Article  CAS  PubMed  Google Scholar 

  58. Pelzer LE, Guardia T, Osvaldo Juarez A, Guerreiro E. Acute and chronic antiinflammatory effects of plant flavonoids. Farmaco. 1998;53(6):421–4. PubMed.

    Article  CAS  PubMed  Google Scholar 

  59. Swingle KF, Shideman FE. Phases of the inflammatory response to subcutaneous implantation of a cotton pellet and their modification by certain anti-inflammatory agents. J Pharmacol Exp Ther. 1972;183(1):226–34. PubMed.

    CAS  PubMed  Google Scholar 

  60. Bryers JD, Jarvis RA, Lebo J, Prudencio A, Kyriakides TR, Uhrich K. Biodegradation of poly (anhydride-esters) into non-steroidal anti-inflammatory drugs and their effect on Pseudomonas aeruginosa biofilms in vitro and on the foreign-body response in vivo. Biomaterials. 2006;27(29):5039–48. PubMed.

    Article  CAS  PubMed  Google Scholar 

  61. Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, et al. Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. J Exp Med. 2006;203(8):1883–9. Pubmed Central PMCID: 2118371.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Hart PH, Whitty GA, Burgess DR, Croatto M, Hamilton JA. Augmentation of glucocorticoid action on human monocytes by interleukin-4. Lymphokine Res. 1990;9(2):147–53. PubMed.

    CAS  PubMed  Google Scholar 

  63. Kruse NJ, Rowe DW, Fujimoto WY, Bornstein P. Inhibitory effects of glucocorticoids on collagen synthesis by mouse sponge granulomas and granuloma fibroblasts in culture. Biochim Biophys Acta. 1978;540(1):101–16. PubMed.

    Article  CAS  PubMed  Google Scholar 

  64. Bhardwaj U, Papadimitrakopoulos F, Burgess DJ. A review of the development of a vehicle for localized and controlled drug delivery for implantable biosensors. J Diabetes Sci Technol. 2008;2(6):1016–29. Pubmed Central PMCID: 2769817.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Norton LW, Koschwanez HE, Wisniewski NA, Klitzman B, Reichert WM. Vascular endothelial growth factor and dexamethasone release from nonfouling sensor coatings affect the foreign body response. J Biomed Mater Res A. 2007;81(4):858–69. Pubmed Central PMCID: 4070388.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Wang Y, Gu B, Burgess DJ. Microspheres prepared with PLGA blends for delivery of dexamethasone for implantable medical devices. Pharm Res. 2014;31(2):373–81. PubMed.

    Article  PubMed  Google Scholar 

  67. Hickey T, Kreutzer D, Burgess DJ, Moussy F. Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices. Biomaterials. 2002;23(7):1649–56. PubMed.

    Article  CAS  PubMed  Google Scholar 

  68. Vallejo-Heligon SG, Klitzman B, Reichert WM. Characterization of porous, dexamethasone-releasing polyurethane coatings for glucose sensors. Acta Biomater. 2014;10(11):4629–38. Pubmed Central PMCID: 4186909.

    Article  CAS  PubMed  Google Scholar 

  69. Acarregui A, Herran E, Igartua M, Blanco FJ, Pedraz JL, Orive G, et al. Multifunctional hydrogel-based scaffold for improving the functionality of encapsulated therapeutic cells and reducing inflammatory response. Acta Biomater. 2014;10(10):4206–16. PubMed.

    Article  CAS  PubMed  Google Scholar 

  70. Vacanti NM, Cheng H, Hill PS, Guerreiro JD, Dang TT, Ma M, et al. Localized delivery of dexamethasone from electrospun fibers reduces the foreign body response. Biomacromolecules. 2012;13(10):3031–8. Pubmed Central PMCID: 3466020.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Wang Y, Vaddiraju S, Qiang L, Xu X, Papadimitrakopoulos F, Burgess DJ. Effect of dexamethasone-loaded poly (lactic-co-glycolic acid) microsphere/poly (vinyl alcohol) hydrogel composite coatings on the basic characteristics of implantable glucose sensors. J Diabetes Sci Technol. 2012;6(6):1445–53. Pubmed Central PMCID: 3570887.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Galeska I, Kim TK, Patil SD, Bhardwaj U, Chatttopadhyay D, Papadimitrakopoulos F, et al. Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels. AAPS J. 2005;7(1):E231–40. Pubmed Central PMCID: 2751512.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Love RJ, Jones KS. Biomaterials, fibrosis, and the use of drug delivery systems in future antifibrotic strategies. Crit Rev Biomed Eng. 2009;37(3):259–81. PubMed.

    Article  PubMed  Google Scholar 

  74. Gancedo M, Ruiz-Corro L, Salazar-Montes A, Rincon AR, Armendariz-Borunda J. Pirfenidone prevents capsular contracture after mammary implantation. Aesthet Plast Surg. 2008;32(1):32–40. PubMed.

    Article  Google Scholar 

  75. Rujitanaroj PO, Jao B, Yang J, Wang F, Anderson JM, Wang J, et al. Controlling fibrous capsule formation through long-term down-regulation of collagen type I (COL1A1) expression by nanofiber-mediated siRNA gene silencing. Acta Biomater. 2013;9(1):4513–24. Pubmed Central PMCID: 3523808.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Takahashi H, Wang Y, Grainger DW. 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. 2010;147(3):400–7. Pubmed Central PMCID: 2975752.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Moore LB, Sawyer AJ, Charokopos A, Skokos EA, Kyriakides TR. Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFkappaB activation in the foreign body response. Acta Biomater. 2015;11:37–47. Pubmed Central PMCID: 4278755.

    Article  CAS  PubMed  Google Scholar 

  78. Uchegbu IF, Schatzlein AG, Tetley L, Gray AI, Sludden J, Siddique S, et al. Polymeric chitosan-based vesicles for drug delivery. J Pharm Pharmacol. 1998;50(5):453–8. PubMed.

    Article  CAS  PubMed  Google Scholar 

  79. de Vos P, Hoogmoed CG, Busscher HJ. Chemistry and biocompatibility of alginate-PLL capsules for immunoprotection of mammalian cells. J Biomed Mater Res. 2002;60(2):252–9. PubMed.

    Article  PubMed  Google Scholar 

  80. Sano A, Hojo T, Maeda M, Fujioka K. Protein release from collagen matrices. Adv Drug Deliv Rev. 1998;31(3):247–66. PubMed.

    Article  PubMed  Google Scholar 

  81. Draye JP, Delaey B, Van de Voorde A, Van Den Bulcke A, De Reu B, Schacht E. In vitro and in vivo biocompatibility of dextran dialdehyde cross-linked gelatin hydrogel films. Biomaterials. 1998;19(18):1677–87. PubMed.

    Article  CAS  PubMed  Google Scholar 

  82. Vercruysse KP, Prestwich GD. Hyaluronate derivatives in drug delivery. Crit Rev Ther Drug Carrier Syst. 1998;15(5):513–55. PubMed.

    Article  CAS  PubMed  Google Scholar 

  83. Quinn CA, Connor RE, Heller A. Biocompatible, glucose-permeable hydrogel for in situ coating of implantable biosensors. Biomaterials. 1997;18(24):1665–70. PubMed.

    Article  CAS  PubMed  Google Scholar 

  84. Vaddiraju S, Wang Y, Qiang L, Burgess DJ, Papadimitrakopoulos F. Microsphere erosion in outer hydrogel membranes creating macroscopic porosity to counter biofouling-induced sensor degradation. Anal Chem. 2012;84(20):8837–45. Pubmed Central PMCID: 3791326.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Vaddiraju S, Singh H, Burgess DJ, Jain FC, Papadimitrakopoulos F. Enhanced glucose sensor linearity using poly (vinyl alcohol) hydrogels. J Diabetes Sci Technol. 2009;3(4):863–74. Pubmed Central PMCID: 2769944.

    Article  PubMed Central  PubMed  Google Scholar 

  86. Patil SD, Papadimitrakopoulos F, Burgess DJ. Dexamethasone-loaded poly (lactic-co-glycolic) acid microspheres/poly (vinyl alcohol) hydrogel composite coatings for inflammation control. Diabetes Technol Ther. 2004;6(6):887–97. PubMed.

    Article  CAS  PubMed  Google Scholar 

  87. Espadas-Torre C, Meyerhoff ME. Thrombogenic properties of untreated and poly (ethylene oxide)-modified polymeric matrices useful for preparing intraarterial ion-selective electrodes. Anal Chem. 1995;67(18):3108–14. PubMed.

    Article  CAS  PubMed  Google Scholar 

  88. Swartzlander MD, Lynn AD, Blakney AK, Kyriakides TR, Bryant SJ. Understanding the host response to cell-laden poly (ethylene glycol)-based hydrogels. Biomaterials. 2013;34(4):952–64. Pubmed Central PMCID: 3683297.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Zhang L, Cao Z, Bai T, Carr L, Ella-Menye JR, Irvin C, et al. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat Biotechnol. 2013;31(6):553–6. PubMed.

    Article  CAS  PubMed  Google Scholar 

  90. Sussman EM, Halpin MC, Muster J, Moon RT, Ratner BD. Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann Biomed Eng. 2014;42(7):1508–16. PubMed.

    Article  PubMed  Google Scholar 

  91. Sandor M, Singh D, Silverman RP, Xu H, De Deyne PG. Comparative host response of 2 human acellular dermal matrices in a primate implant model. Eplasty. 2014;14:e7. Pubmed Central PMCID: 3914385.

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the US Army Medical Research and Materiel Command, Telemedicine & Advanced Technology Research Center (Awards W81XWH-07-1-0668 and W81XWH-09-1-0711) for financial support.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, U3092, Storrs, CT, 06269, USA

    Michail Kastellorizios, Namita Tipnis & Diane J. Burgess

Authors
  1. Michail Kastellorizios
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Namita Tipnis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diane J. Burgess
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diane J. Burgess .

Editor information

Editors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Kristina N. Ekdahl

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

  4. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Bo Nilsson

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this paper

Cite this paper

Kastellorizios, M., Tipnis, N., Burgess, D.J. (2015). Foreign Body Reaction to Subcutaneous Implants. In: Lambris, J., Ekdahl, K., Ricklin, D., Nilsson, B. (eds) Immune Responses to Biosurfaces. Advances in Experimental Medicine and Biology, vol 865. Springer, Cham. https://doi.org/10.1007/978-3-319-18603-0_6

Download citation

Publish with us

Policies and ethics

Search

Navigation