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Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response

  • Review Article
  • Theme: Critical Variables in the In Vitro and In Vivo Performance of Parenteral Sustained Release Products
  • Published:
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Abstract

In recent years, a variety of biomaterial implantable devices has been developed. Of particular significance to pharmaceutical sciences is the progress made on the development of drug/implantable device combination products. However, the clinical application of these devices is still a critical issue due to the host response, which results from both the tissue trauma during implantation and the presence of the device in the body. Accordingly, the in vivo functionality and durability of any implantable device can be compromised by the body response to the foreign material. Numerous strategies to overcome negative body reactions have been reported. The aim of this review is to outline some key issues of biomaterial/tissue interactions such as foreign body response and biocompatibility and biocompatibility assessment. In addition, general approaches used to overcome the in vivo instability of implantable devices are presented, including (a) biocompatible material coatings, (b) steroidal and nonsteroidal anti-inflammatory drugs, and (c) angiogenic drugs. In particular, strategies to overcome host response to glucose biosensors are summarized.

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References

  1. Prokop A. Bioartificial organs in the twenty-first century: nano-biological devices. Ann NY Acad Sci. 2001;944:472–90.

    CAS  PubMed  Google Scholar 

  2. Wilson GS, Zhang Y, Reach G, Moatti-Sirat D, Poitout V, Thévenot DR, et al. Progress toward the development of an implantable sensor for glucose. Clin Chem. 1992;38(9):1613–7.

    CAS  PubMed  Google Scholar 

  3. Klonoff DC. Technological advances in the treatment of diabetes mellitus: better bioengineering begets benefits in glucose measurement, the artificial pancreas, and insulin delivery. Pediatr Endocrinol Rev. 2003;1(2):94–100.

    PubMed  Google Scholar 

  4. Koschwanez HE, Reichert WM. In vitro, in vivo and post explantation testing of glucose-detecting biosensors: current methods and recommendations. Biomaterials. 2007;28(25):3687–703.

    Article  CAS  PubMed  Google Scholar 

  5. Bailey TS, Zisser HC, Garg SK. Reduction in hemoglobin A1C with real-time continuous glucose monitoring: results from a 12-week observational study. Diabetes Technol Ther. 2007;9(3):203–10.

    Article  CAS  PubMed  Google Scholar 

  6. Buckingham B, Caswell K, Wilson DM. Real-time continuous glucose monitoring. Curr Opin Endocrinol Diabetes Obes. 2007;14(4):288–95.

    CAS  PubMed  Google Scholar 

  7. Callahan 4th TD, Natale A. Catheter ablation of atrial fibrillation. Med Clin North Am. 2008;92(1):179–201. xii.

    Article  PubMed  Google Scholar 

  8. Black MM, Drury PJ. Mechanical and other problems of artificial valves. Curr Top Pathol. 1994;86:127–59.

    CAS  PubMed  Google Scholar 

  9. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci. 2004;4(8):743–65.

    Article  CAS  PubMed  Google Scholar 

  10. Matsumoto T, Okazaki M, Nakahira A, Sasaki J, Egusa H, Sohmura T. Modification of apatite materials for bone tissue engineering and drug delivery carriers. Curr Med Chem. 2007;14(25):2726–33.

    Article  CAS  PubMed  Google Scholar 

  11. Kipshidze NN, Tsapenko MV, Leon MB, Stone GW, Moses JW. Update on drug-eluting coronary stents. Expert Rev Cardiovasc Ther. 2005;3(5):953–68.

    Article  CAS  PubMed  Google Scholar 

  12. Williams DF. Tissue–biomaterial interactions. J Mater Sci. 1987;22:3421–45.

    Article  CAS  Google Scholar 

  13. Laurencin CT, Elgendy H. The biocompatibility and toxicity of degradable polymeric materials: implication for drug delivery. In: Domb A, Maniar M, editors. Site specific drug delivery. New York: Wiley; 1994. p. 27–46.

    Google Scholar 

  14. Anderson JM. Biological responses to materials. Annu Rev Mater Res. 2001;31:81–110.

    Article  CAS  Google Scholar 

  15. Fournier E, Passirani C, Montero-Menei CN, Benoit JP. Biocompatibility of implantable synthetic polymeric drug carriers: focus on brain biocompatibility. Biomaterials. 2003;24(19):3311–31.

    Article  CAS  PubMed  Google Scholar 

  16. Arshady R. Polymeric biomaterials: chemistry, concepts, criteria. In: Arshady R, editor. Introduction to polymeric biomaterials: the polymeric biomaterials series. London: Citus Books; 2003. p. 1–62.

    Google Scholar 

  17. Ratner BA, Horbett TA. Some background concepts. In: Ratner BD, Schoen FJ, Lemons JE, editors. Biomaterials science: an introduction to materials in medicine. 2nd ed. San Diego: Elsevier; 2004. p. 237.

    Google Scholar 

  18. Anderson JM. Inflammatory response to implants. ASAIO Trans. 1988;34(2):101–7.

    Article  CAS  PubMed  Google Scholar 

  19. Ziats NP, Miller KM, Anderson JM. In vitro and in vivo interactions of cells with biomaterials. Biomaterials. 1988;9(1):5–13.

    Article  CAS  PubMed  Google Scholar 

  20. Pappas N. An introduction to materials in medicine. Biomaterials science. New York: Academic; 1996. p. 60–4.

    Google Scholar 

  21. Schoen FJ, Anderson JM. Host response to biomaterials and their evaluation. In: Ratner BD, Schoen FJ, Lemons JE, editors. Biomaterials science: an introduction to materials in medicine, 2nd. San Diego: Elsevier; 2004. p. 293–6.

    Google Scholar 

  22. Sieminski AL, Gooch KJ. Biomaterial–microvasculature interactions. Biomaterials. 2000;21(22):2232–41.

    Article  CAS  PubMed  Google Scholar 

  23. Mitchell RN, Cotran RS. Acute and chronic inflammation in Robbins basic pathology. Philadelphia: Saunders; 2002. p. 33–60.

    Google Scholar 

  24. Ratner BD, Bryant SJ. Biomaterials: where we have been and where we are going. Annu Rev Biomed Eng. 2004;6:41–75.

    Article  CAS  PubMed  Google Scholar 

  25. Jutila MA. Leukocyte traffic to sites of inflammation. APMIS. 1992;100(3):191–201.

    Article  CAS  PubMed  Google Scholar 

  26. Pober JS, Cotran RS. The role of endothelial cells in inflammation. Transplantation. 1990;50(4):537–44.

    Article  CAS  PubMed  Google Scholar 

  27. Williams GT, Williams WJ. Granulomatous inflammation—a review. J Clin Pathol. 1983;36(7):723–73.

    Article  CAS  PubMed  Google Scholar 

  28. Wahl SM, Wong H, McCartney-Francis N. Role of growth factors in inflammation and repair. J Cell Biochem. 1989;40(2):193–9.

    Article  CAS  PubMed  Google Scholar 

  29. Johnston Jr RB. Current concepts: immunology, monocytes and macrophages. N Engl J Med. 1988;318(12):747–52.

    Article  PubMed  Google Scholar 

  30. Kovacs EJ. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today. 1991;12(1):17–23.

    Article  CAS  PubMed  Google Scholar 

  31. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem. 1991;45(4):319–26.

    Article  CAS  PubMed  Google Scholar 

  32. Labat-Robert J, Bihari-Varga M, Robert L. Extracellular matrix. FEBS Lett. 1990;268(2):386–93.

    Article  CAS  PubMed  Google Scholar 

  33. Anderson JM, Langone JJ. Issues and perspectives on the biocompatibility and immunotoxicity evaluation of implanted controlled release systems. J Control Release. 1999;57(2):107–13.

    Article  CAS  PubMed  Google Scholar 

  34. Mikos AG, McIntire LV, Anderson JM, Babensee JE. Host response to tissue engineered devices. Adv Drug Deliv Rev. 1998;33(1–2):111–39.

    PubMed  Google Scholar 

  35. Saad B, Abu-Hijleh G, Suter UW. Polymer biocompatibility assessment by cell culture techniques. In: Arshady R, editor. Introduction to polymeric biomaterials: the polymeric biomaterials series. London: Citus Books; 2003. p. 263–99.

    Google Scholar 

  36. Ratner BD, Northup SJ, Anderson JM. Biological testing of biomaterials. In: Ratner BD, Schoen FJ, Lemons JE, editors. Biomaterials science: an introduction to materials in medicine. 2nd ed. San Diego: Elsevier; 2004. p. 355–60.

    Google Scholar 

  37. Dekker A, Panfil C, Valdor M, Richter H, Mittermayer Ch, Kirkpatrick CJ. Quantitative methods for in vitro cytotoxicity testing of biomaterials. Cells Mater. 1994;4:101–12.

    CAS  Google Scholar 

  38. Kirkpatrick CJ, Bittinger F, Wagner M, Köhler H, van Kooten TG, Klein CL, et al. Current trends in biocompatibility testing. Proc Inst Mech Eng [H]. 1998;212(2):75–84.

    CAS  Google Scholar 

  39. Royals MA, Fujita SM, Yewey GL, Rodriguez J, Schultheiss PC, Dunn RL. Biocompatibility of a biodegradable in situ forming implant system in rhesus monkeys. J Biomed Mater Res. 1999;45(3):231–9.

    Article  CAS  PubMed  Google Scholar 

  40. ISO 10,933. Biological evaluation of medical devices. Geneva: International Standards Organizations; 1992.

    Google Scholar 

  41. Association for the Advancement of Medical Instrumentation. AAMI standards and recommended practices. Biological evaluation of medical devices, v.4., Suppl. Arlington: AAMI; 1997.

    Google Scholar 

  42. FDA. Blue Book Memorandum G95–1: FDA-modified version of ISO10, 933—part 1, biological evaluation of medical devices. Silver Spring: FDA; 1996.

    Google Scholar 

  43. US Pharmacopeia. Biological reactivity tests in vitro. In: US Pharmacopeia XXIII, editor. United States Pharmacopeial Convention, Inc., Rockville, MD, v.27. Rockville: US Pharmacopeia; 1995. p. 2173–5.

    Google Scholar 

  44. Hoffman AS, Cooper SL, Visser SA, Hergenrother RW, Lamba NMK, Peppas NA, et al. Classes of materials used in medicine. In: Ratner BD, Schoen FJ, Lemons JE, editors. Biomaterials science: an introduction to materials in medicine. 2nd ed. San Diego: Elsevier; 2004. p. 67–127.

    Google Scholar 

  45. Göpferich A. Polymer degradation and erosion: mechanisms and applications. Eur J Pharm Biopharm. 1996;42(1):1–11.

    Google Scholar 

  46. Shastri VP. Non-degradable biocompatible polymers in medicine: past, present and future. Current Pharm Biotech. 2003;4:331–7.

    Article  CAS  Google Scholar 

  47. Wisniewski N, Reichert M. Methods for reducing biosensor membrane biofouling. Colloids Surf B Biointerfaces. 2000;18(3–4):197–219.

    Article  CAS  PubMed  Google Scholar 

  48. Shen M, Horbett TA. The effects of surface chemistry and adsorbed proteins on monocyte /macrophage adhesion to chemically modified polystyrene surfaces. J Biomed Mater Res. 2001;57(3):336–45.

    Article  CAS  PubMed  Google Scholar 

  49. Dalsin JL, Hu BH, Lee BP, Messersmith PB. Mussel adhesive protein mimetic polymers for the preparation of nonfouling surfaces. J Am Chem Soc. 2003;125(14):4253–8.

    Article  CAS  PubMed  Google Scholar 

  50. 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.

    Article  PubMed  CAS  Google Scholar 

  51. Uchegbu IF, Schätzlein 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.

    CAS  PubMed  Google Scholar 

  52. Borchard G, Junginger HE. Modern drug delivery applications of chitosan. Adv Drug Deliv Rev. 2001;52(2):103.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  54. Geiger M, Li RH, Friess W. Collagen sponges for bone regeneration with rhBMP-2. Adv Drug Deliv Rev. 2003;55(12):1613–29.

    Article  CAS  PubMed  Google Scholar 

  55. 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.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  57. Athanasiou KA, Niederauer GG, Agrawal CM. Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers. Biomaterials. 1996;17(2):93–102.

    Article  CAS  PubMed  Google Scholar 

  58. Shive MS, Anderson JM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Delivery Rev. 1997;28(1):5–24.

    Article  Google Scholar 

  59. Quinn CP, Pathak CP, Heller A, Hubbell JA. Photo-crosslinked copolymers of 2-hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors. Biomaterials. 1995;16(5):389–96.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. Paradossi G, Cavalieri F, Chiessi E, Spagnoli C, Cowman MK. Poly(vinyl alcohol) as versatile biomaterial for potential biomedical applications. J Mater Sci Mater Med. 2003;14(8):687–91.

    Article  CAS  PubMed  Google Scholar 

  62. Maruoka S, Matsuura T, Kawasaki K, Okamoto M, Yoshiaki H, Kodama M, et al. Biocompatibility of poly-vinyl-alcohol gel as a vitreous substitute. Curr Eye Res. 2006;31(7–8):599–606.

    Article  CAS  PubMed  Google Scholar 

  63. Kost J, Langer R. Equilibrium swollen hydrogels in controlled release applications. In: Peppas NA, editor. Hydrogels in medicine and pharmacy, v.3. Boca Raton: CRC; 1997. p. 95–108.

    Google Scholar 

  64. Ravin AG, Olbrich KC, Levin LS, Usala AL, Klizman B. Long-and short-term effects of biological hydrogels on capsule microvascular density around implants in rats. J Biomed Mater Res. 2001;58:313–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  66. Hickey T, Kreutzer D, Burgess DJ, Moussy F. In vivo evaluation of a dexamethasone/PLGA microsphere system designed to suppress the inflammatory tissue response to implantable medical devices. J Biomed Mater Res. 2002;61(2):180–7.

    Article  CAS  PubMed  Google Scholar 

  67. 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.

    Article  CAS  PubMed  Google Scholar 

  68. 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.

    Article  CAS  PubMed  Google Scholar 

  69. Norton LW, Tegnell E, Topored SS, Reichert WM. In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings. Biomaterials. 2005;26(16):3285–97.

    Article  CAS  PubMed  Google Scholar 

  70. Norton LW, Koschwanez HE, Wisniewski NA, Klitzman B, Reichert WM. Vascular endothelial grown factor and dexamethasone release from non-fouling sensor coating affect the foreign body response. J Bio Mater Res A. 2007;81(4):858–69.

    Article  CAS  Google Scholar 

  71. Patil SD, Papadimitrakopouos F, Burgess DJ. Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. J Control Release. 2007;117:68–79.

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  73. Bhardwaj U, Radhacirsshana S, Papadimitrakopoulos F, Burgess DJ. PLGA/PVA hydrogel composites for long-term inflammation control following s.c. implantation. Int J Pham. 2010;484:78–86.

    Article  CAS  Google Scholar 

  74. Perreti M, Ahluwalia A. The microcirculation and inflammation: site of action for glucocorticoids. Microcirculation. 2000;7:147–61.

    Google Scholar 

  75. Strecker EP, Gabelmann A, Boos I, Lucas C, Xu Z, Haberstroh J, et al. Effect on intimal hyperplasia of dexamethasone released from coated metal stents compared with non-coated stents in canine femoral arteries. Cardiovasc Intervent Radiol. 1998;21(6):487–96.

    Article  CAS  PubMed  Google Scholar 

  76. Ronneberger B, Kissel T, Anderson JM. Biocompatibility of ABA triblock copolymer microparticles consisting of poly(L-lactic-co-glycolic-acid) A-blocks attached to central poly(oxyethylene) B-blocks in rats after intramuscular injection. Eur J Pharm Biopharm. 1997;43:19–28.

    Article  CAS  Google Scholar 

  77. Daugherty AL, Cleland JL, Duenas EM, Mrsny RJ. Pharmacological modulation of the tissue response to implanted polylactic-co-glycolic acid microspheres. Eur J Pharm Biopharm. 1997;44(1):89–102.

    Article  CAS  Google Scholar 

  78. Lunsford L, McKeever U, Eckstein V, Hedley ML. Tissue distribution and persistence in mice of plasmid DNA encapsulated in a PLGA-based microsphere delivery vehicle. J Drug Target. 2000;8(1):39–50.

    Article  CAS  PubMed  Google Scholar 

  79. 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;23:1649–56.

    Article  CAS  PubMed  Google Scholar 

  80. Kyrolainen M, Rigsby P, Eddy S, Vadgama P. Bio-/hemocompatibility: implications and outcomes for sensors? Acta Anaesthesiol Scand Suppl. 1995;104:55–60.

    Article  CAS  PubMed  Google Scholar 

  81. Gerritsen M, Jansen JA, Kros A, Vriezema DM, Sommerdijk NA, Nolte RJ, et al. Influence of inflammatory cells and serum on the performance of implantable glucose sensors. J Biomed Mater Res. 2001;54(1):69–75.

    Article  CAS  PubMed  Google Scholar 

  82. Tanihara M, Suzuki Y, Yamamoto E, Noguchi A, Mizushima Y. Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently cross-linked gel of heparin and alginate. J Biomed Mater Res. 2001;56:216–21.

    Article  CAS  PubMed  Google Scholar 

  83. Ward WK, Quinn MJ, Wood MD, Tiekotter KL, Pidikiti S, Gallagher JA. Vascularizing the tissue surrounding a model biosensor: how localized is the effect of a subcutaneous infusion of vascular endothelial growth factor (VEGF)? Biosens Bioelectron. 2003;19:155–63.

    Article  CAS  PubMed  Google Scholar 

  84. Kedem A, Perets A, Gamlieli-Bonshtein I, Dvir-Ginzberg M, Mizrahi S, Cohen S. Vascular endothelial growth factor-releasing enhance vascularization and engraftment of hepatocytes transplanted on liver lobes. Tissue Eng. 2005;11:715–22.

    Article  CAS  PubMed  Google Scholar 

  85. Gaytan F, Morales C, Bellido C, Sanchez-Criado JE. Selective apoptosis of luteal endothelial cells in dexamethasone-treated rats leads to ischemic necrosis of luteal tissue. Biol Reprod. 2002;66:232–40.

    Article  CAS  PubMed  Google Scholar 

  86. Halaby IA, Lyden SP, Davies MG, Roztocil E, Salamone LJ, Brooks AI. Glucocorticoid-regulated VEGF expression in ischemic skeletal muscle. Molec Ther. 2002;5(3):300–6.

    Article  CAS  Google Scholar 

  87. Reach G, Wilson GS. Can continuous glucose monitoring be used for the treatment of diabetes? Anal Chem. 1992;64(6):381A–6.

    Article  CAS  PubMed  Google Scholar 

  88. Rebrin K, Fischer U, Hahn von Dorsche H, von Woetke T, Abel P, Brunstein E. Subcutaneous glucose monitoring by means of electrochemical sensors: fiction or reality. J Biomed Eng. 1992;14(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  89. Bobbioni-Harsch E, Rohner-Jeanrenaud F, Koudelka M, de Rooij N, Jeanrenaud B. Lifespan of subcutaneous glucose sensors and their performances during dynamic glycemia changes in rats. J Biomed Eng. 1993;15(6):457–63.

    Article  CAS  PubMed  Google Scholar 

  90. Gilligan BJ, Shults MC, Rhodes RK, Updike SJ. Evaluation of a subcutaneous glucose sensor out to 3 months in a dog model. Diabetes Care. 1994;17(8):882–7.

    Article  CAS  PubMed  Google Scholar 

  91. Gerritsen M, Kros A, Srpakel V, Lutterman JA, Notle RJM, Jansen JA. Biocompatibility evaluation of sol–gel coating for subcutaneously implantable glucose sensors. Biomaterials. 2000;21:71–8.

    Article  CAS  PubMed  Google Scholar 

  92. Yu B, Wang C, Ju YM, West L, Harmon J, Moussy Y, et al. Use of hydrogel coating to improve the performance of implanted glucose sensors. Biosens Bioelectron. 2008;23(8):1278–84.

    Article  CAS  PubMed  Google Scholar 

  93. Wilson GS, Gifford R. Biosensors for real-time measurements in vivo. Biosens Bioelectron. 2005;20:2388–403.

    Article  CAS  PubMed  Google Scholar 

  94. Rigby G, Ahmed S, Horseman G, Vadgama P. In vivo glucose monitoring with open microflow—influences of fluid composition and preliminary evaluation in man. Anal Chim Acta. 1999;385:23–32.

    Article  CAS  Google Scholar 

  95. 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 Tech. 2008;2(6):1016–29.

    Google Scholar 

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Acknowledgments

The authors thank TATRC (Grant # W81XWH0710688) and NIH (Grant # R21HL90458-01) for financial support.

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Correspondence to Diane J. Burgess.

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Morais, J.M., Papadimitrakopoulos, F. & Burgess, D.J. Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response. AAPS J 12, 188–196 (2010). https://doi.org/10.1208/s12248-010-9175-3

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