Skip to main content

Advertisement

SpringerLink
Log in

Engineering biomaterials to prevent post-operative infection and fibrosis

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Implantable biomaterials are essential surgical devices, extending and improving the quality of life of millions of people globally. Advances in materials science, manufacturing, and in our understanding of the biological response to medical device implantation over several decades have resulted in improved safety and functionality of biomaterials. However, post-operative infection and immune responses remain significant challenges that interfere with biomaterial functionality and host healing processes. The objectives of this review is to provide an overview of the biology of post-operative infection and the physiological response to implanted biomaterials and to discuss emerging strategies utilizing local drug delivery and surface modification to improve the long-term safety and efficacy of biomaterials.

Graphical abstract

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Wang X. Overview on biocompatibilities of implantable biomaterials. Adv Biomater Sci Biomed App Biomed; Lazinica, R, Ed. 2013;111–55.

  2. Kang C-W, Fang F-Z. State of the art of bioimplants manufacturing: part II. Adv Manuf. 2018;6(2):137–54.

    Article  CAS  Google Scholar 

  3. Gristina AG. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science. 1987;237(4822):1588–95.

    Article  CAS  PubMed  Google Scholar 

  4. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for disease control and prevention guideline for the prevention of surgical site infection,. JAMA surgery. 2017;152(8):784–91.

    Article  PubMed  Google Scholar 

  5. Schierholz J, Beuth J. Implant infections: a haven for opportunistic bacteria. J Hosp Infect. 2001;49(2):87–93.

    Article  CAS  Google Scholar 

  6. Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med. 2004;350(14):1422–9.

    Article  CAS  Google Scholar 

  7. Arefian H, Vogel M, Kwetkat A, Hartmann M. Economic evaluation of interventions for prevention of hospital acquired infections: a systematic review. PloS One. 2016;11(1):e0146381.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Founou RC, Founou LL, Essack SY. Clinical and economic impact of antibiotic resistance in developing countries: a systematic review and meta-analysis. PloS One. 2017;12(12):e0189621.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Giraldi G, Montesano M, Sandorfi F, Iachini M, Orsi G. Excess length of hospital stay due to healthcare acquired infections: methodologies evaluation. Ann Ig. 2019;31(5):507–16.

    CAS  PubMed  Google Scholar 

  10. Amin Yavari S, Castenmiller SM, van Strijp JA. Croes M. Combating Implant Infections: Shifting Focus from Bacteria to Host. Adv Mater; 2020. p. 2002962.

    Google Scholar 

  11. VanEpps JS, Younger JG. Implantable device related infection. Shock (Augusta, Ga). 2016;46(6):597.

    Article  PubMed Central  Google Scholar 

  12. Arciola CR, Campoccia D, Speziale P, Montanaro L, Costerton JW. Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials. Biomaterials. 2012;33(26):5967–82.

  13. López D, Vlamakis H, Kolter R. Biofilms. Cold Spring Harb Perspec Biol. 2010;2(7):a000398.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mack D. Molecular mechanisms of Staphylococcus epidermidis biofilm formation. J Hosp Infect. 1999;43:S113–25.

    Article  Google Scholar 

  15. Prince AS. Biofilms, antimicrobial resistance, and airway infection. N Engl J Med. 2002;347(14):1110–1.

    Article  Google Scholar 

  16. Rao RS, Karthika RU, Singh S, Shashikala P, Kanungo R, Jayachandran S, et al. Correlation between biofilm production and multiple drug resistance in imipenem resistant clinical isolates of Acinetobacter baumannii. Indian J Med Microbiol. 2008;26(4):333.

    Article  PubMed  Google Scholar 

  17. Wiegering A, Sinha B, Spor L, Klinge U, Steger U, Germer C, et al. Gentamicin for prevention of intraoperative mesh contamination: demonstration of high bactericide effect (in vitro) and low systemic bioavailability (in vivo). Hernia. 2014;18(5):691–700.

    Article  CAS  PubMed  Google Scholar 

  18. Xiong M-H, Bao Y, Yang X-Z, Zhu Y-H, Wang J. Delivery of antibiotics with polymeric particles. Advanced drug delivery reviews. 2014;78:63–76.

    Article  CAS  PubMed  Google Scholar 

  19. Jamaledin R, Yiu CK, Zare EN, Niu LN, Vecchione R, Chen G, et al. Advances in antimicrobial microneedle patches for combating infections. Adv Mater. 2020;32(33):2002129.

    Article  CAS  Google Scholar 

  20. Heta S, Robo I. The side effects of the most commonly used group of antibiotics in periodontal treatments. Med Sci. 2018;6(1):6.

    Article  PubMed Central  Google Scholar 

  21. Francis NA, Gillespie D, Nuttall J, Hood K, Little P, Verheij T, et al. Antibiotics for acute cough: an international observational study of patient adherence in primary care. Br J Gen Pract. 2012;62(599):e429–37.

    Article  Google Scholar 

  22. Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock SJ, Wines RC, et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012;157(11):785–95.

    Article  PubMed  Google Scholar 

  23. Heuer H, Krögerrecklenfort E, Wellington E, Egan S, Van Elsas J, Van Overbeek L, et al. Gentamicin resistance genes in environmental bacteria: prevalence and transfer. FEMS Microbiol Ecol. 2002;42(2):289–302.

    Article  CAS  PubMed  Google Scholar 

  24. Berger-Bächi B, Rohrer S. Factors influencing methicillin resistance in staphylococci. Arch Microbiol. 2002;178(3):165–71.

    Article  PubMed  Google Scholar 

  25. Price LB, Stegger M, Hasman H, Aziz M, Larsen J, Andersen PS, et al. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. MBio. 2012;3(1).

  26. Yazdankhah SP, Scheie AA, Høiby EA, Lunestad B-T, Heir E, Fotland TØ, et al. Triclosan and antimicrobial resistance in bacteria: an overview. Microb Drug Resist. 2006;12(2):83–90.

    Article  CAS  PubMed  Google Scholar 

  27. Costerton JW, Cheng K, Geesey GG, Ladd TI, Nickel JC, Dasgupta M, et al. Bacterial biofilms in nature and disease. Ann Rev Microbiol. 1987;41(1):435–64.

    Article  CAS  Google Scholar 

  28. An YH, Dickinson RB, Doyle RJ. Mechanisms of bacterial adhesion and pathogenesis of implant and tissue infections. Handbook of Bacterial Adhesion: Springer; 2000. p. 1–27.

    Google Scholar 

  29. Fletcher M, Savage DC. Bacterial adhesion: mechanisms and physiological significance: Springer Science & Business Media; 2013.

  30. Dunne WM. Bacterial adhesion: seen any good biofilms lately? Clin Microbiol Rev. 2002;15(2):155–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Costerton JW, Lappin-Scott HM. Introduction to microbial biofilms. Microb Biofilms. 1995;1–11.

  32. Vega NM, Gore J. Collective antibiotic resistance: mechanisms and implications. Curr Opin Microbiol. 2014;21:28–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lewis K. Multidrug tolerance of biofilms and persister cells. Bacterial biofilms: Springer; 2008. p. 107–31.

    Google Scholar 

  34. Cai Z, Wang Y, Zhu L-J, Liu Z-Q. Nanocarriers: a general strategy for enhancement of oral bioavailability of poorly absorbed or pre-systemically metabolized drugs. Curr Drug Metabol. 2010;11(2):197–207.

    Article  CAS  PubMed  Google Scholar 

  35. Lee JW, Prausnitz MR. Drug delivery using microneedle patches: not just for skin. Taylor & Francis; 2018.

  36. Teo AJ, Mishra A, Park I, Kim Y-J, Park W-T, Yoon Y-J. Polymeric biomaterials for medical implants and devices. ACS Biomater Sci Eng. 2016;2(4):454–72.

    Article  CAS  Google Scholar 

  37. Balaji AB, Pakalapati H, Khalid M, Walvekar R, Siddiqui H. Natural and synthetic biocompatible and biodegradable polymers. Biodegradable and biocompatible polymer composites: processing, properties and applications Woodhead Publishing series in composites science and engineering Duxford: Woodhead Publishing. 2017:3–32.

  38. Pappalardo D, Mathisen Tr, Finne-Wistrand A. Biocompatibility of resorbable polymers: a historical perspective and framework for the future. Biomacromolecules. 2019;20(4):1465–77.

  39. Rebelo R, Fernandes M, Fangueiro R. Biopolymers in medical implants: a brief review. Procedia Eng. 2017;200:236–43.

    Article  CAS  Google Scholar 

  40. Sionkowska A. Current research on the blends of natural and synthetic polymers as new biomaterials. Prog Polym Sci. 2011;36(9):1254–76.

    Article  CAS  Google Scholar 

  41. Suhardi V, Bichara D, Kwok S, Freiberg A, Rubash H, Malchau H, et al. A fully functional drug-eluting joint implant. Nat Biomed Eng. 2017;1(6):1–11.

    Article  Google Scholar 

  42. Association AO. Hip and Knee Arthroplasty. Annual report 2013. Adelaide: AOA; 2015.

  43. Burnett RSJ, Kelly MA, Hanssen AD, Barrack RL. Technique and timing of two-stage exchange for infection in TKA. Clin Orthop Relat Res 1976-2007;464:164–78.

  44. Ashbaugh AG, Jiang X, Zheng J, Tsai AS, Kim W-S, Thompson JM, et al. Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo. Proc Natl Acad Sci. 2016;113(45):E6919–28.

    Article  CAS  Google Scholar 

  45. Kehinde EO, Rotimi VO, Al-Awadi KA, Abdul-Halim H, Boland F, Al-Hunayan A, et al. Factors predisposing to urinary tract infection after J ureteral stent insertion. J Urol. 2002;167(3):1334–7.

    Article  PubMed  Google Scholar 

  46. Chew BH, Lange D. Ureteral stent symptoms and associated infections: a biomaterials perspective. Nat Rev Urol. 2009;6(8):440.

    Article  PubMed  Google Scholar 

  47. Cadieux PA, Chew BH, Knudsen BE, DeJong K, Rowe E, Reid G, et al. Triclosan loaded ureteral stents decrease proteus mirabilis 296 infection in a rabbit urinary tract infection model. J Urol. 2006;175(6):2331–5.

    Article  PubMed  Google Scholar 

  48. Chuanchuen R, Karkhoff-Schweizer RR, Schweizer HP. High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux. Am J Infect Cont. 2003;31(2):124–7.

    Article  PubMed  Google Scholar 

  49. Fan F, Yan K, Wallis NG, Reed S, Moore TD, Rittenhouse SF, et al. Defining and combating the mechanisms of triclosan resistance in clinical isolates of Staphylococcus aureus. Antimicrob Agen Chemother. 2002;46(11):3343–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mcmurry LM, Oethinger M, Levy SB. Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli. FEMS Microbiol Lett. 1998;166(2):305–9.

    Article  CAS  PubMed  Google Scholar 

  51. Minardi D, Ghiselli R, Cirioni O, Giacometti A, Kamysz W, Orlando F, et al. The antimicrobial peptide Tachyplesin III coated alone and in combination with intraperitoneal piperacillin-tazobactam prevents ureteral stent Pseudomonas infection in a rat subcutaneous pouch model. Peptides. 2007;28(12):2293–8.

    Article  CAS  PubMed  Google Scholar 

  52. Alves P, Gomes L, Vorobii M, Rodríguez-Emmenegger C, Mergulhão F. The potential advantages of using a poly (HPMA) brush in urinary catheters: effects on biofilm cells and architecture. Colloids Surf B. 2020;191:110976.

    Article  CAS  PubMed  Google Scholar 

  53. Orlando F, Ghiselli R, Cirioni O, Minardi D, Tomasinsig L, Mocchegiani F, et al. BMAP-28 improves the efficacy of vancomycin in rat models of gram-positive cocci ureteral stent infection. Peptides. 2008;29(7):1118–23.

    Article  CAS  PubMed  Google Scholar 

  54. Cirioni O, Ghiselli R, Silvestri C, Minardi D, Gabrielli E, Orlando F, et al. Effect of the combination of clarithromycin and amikacin on Pseudomonas aeruginosa biofilm in an animal model of ureteral stent infection. J Antimicrob Chemother. 2011;66(6):1318–23.

    Article  CAS  Google Scholar 

  55. Apisarnthanarak A, Singh N, Bandong AN, Madriaga G. Triclosan-coated sutures reduce the risk of surgical site infections: a systematic review and meta-analysis. Infect Cont Hosp Epidemiol. 2015;36(2):169–79.

  56. Leaper D, Wilson P, Assadian O, Edmiston C, Kiernan M, Miller A, et al. The role of antimicrobial sutures in preventing surgical site infection. Ann R Coll Surg Engl. 2017;99(6):439–43.

    Article  CAS  PubMed  Google Scholar 

  57. Rothenburger S, Spangler D, Bhende S, Burkley D. In vitro antimicrobial evaluation of Coated VICRYL* Plus Antibacterial Suture (coated polyglactin 910 with triclosan) using zone of inhibition assays. Surg Infect. 2002;3(S1):s79–87.

    Article  PubMed  Google Scholar 

  58. Chen X, Hou D, Wang L, Zhang Q, Zou J, Sun G. Antibacterial surgical silk sutures using a high-performance slow-release carrier coating system. ACS Appl Mater Interfaces. 2015;7(40):22394–403.

    Article  CAS  Google Scholar 

  59. Kashiwabuchi F, Parikh KS, Omiadze R, Zhang S, Luo L, Patel HV, et al. Development of absorbable, antibiotic-eluting sutures for ophthalmic surgery. Trans Vis Sci Technol. 2017;6(1):1.

  60. Bae S, DiBalsi MJ, Meilinger N, Zhang C, Beal E, Korneva G, et al. Heparin-eluting electrospun nanofiber yarns for antithrombotic vascular sutures. ACS Appl Mater Interfaces. 2018;10(10):8426–35.

    Article  CAS  Google Scholar 

  61. Chen S, Ge L, Mueller A, Carlson MA, Teusink MJ, Shuler FD, et al. Twisting electrospun nanofiber fine strips into functional sutures for sustained co-delivery of gentamicin and silver. Nanomed Nanotech Biol Med. 2017;13(4):1435–45.

  62. He CL, Huang ZM, Han XJ. Fabrication of drug-loaded electrospun aligned fibrous threads for suture applications. Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials. 2009;89(1):80–95.

    Article  Google Scholar 

  63. Padmakumar S, Joseph J, Neppalli MH, Mathew SE, Nair SV, Shankarappa SA, et al. Electrospun polymeric core–sheath yarns as drug eluting surgical sutures. ACS Appl Mater Interfaces. 2016;8(11):6925–34.

    Article  CAS  Google Scholar 

  64. Weldon CB, Tsui JH, Shankarappa SA, Nguyen VT, Ma M, Anderson DG, et al. Electrospun drug-eluting sutures for local anesthesia. J Control Release. 2012;161(3):903–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Parikh KS, Omiadze R, Josyula A, Shi R, Anders NM, He P, et al. Ultra‐thin, High Strength, Antibiotic‐eluting Sutures for Prevention of Ophthalmic Infection. Bioengn Transl Med. 2020:e10204.

  66. Hizal F, Rungraeng N, Lee J, Jun S, Busscher HJ, van der Mei HC, et al. Nanoengineered superhydrophobic surfaces of aluminum with extremely low bacterial adhesivity. ACS Appl Mater Interfaces. 2017;9(13):12118–29.

    Article  CAS  Google Scholar 

  67. Zhang X, Wang L, Levänen E. Superhydrophobic surfaces for the reduction of bacterial adhesion. Rsc Adv. 2013;3(30):12003–20.

    Article  CAS  Google Scholar 

  68. Song F, Koo H, Ren D. Effects of material properties on bacterial adhesion and biofilm formation. Journal Dent Res. 2015;94(8):1027–34.

    Article  CAS  PubMed  Google Scholar 

  69. Quirynen Mv, Van Der Mei H, Bollen C, Schotte A, Marechal M, Doornbusch G, et al. An in vivo study of the influence of the surface roughness of implants on the microbiology of supra-and subgingival plaque. J Dent Res. 1993;72(9):1304–9.

  70. Hsu LC, Fang J, Borca-Tasciuc DA, Worobo RW, Moraru CI. Effect of micro-and nanoscale topography on the adhesion of bacterial cells to solid surfaces. Appl Environ Microbiol. 2013;79(8):2703–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Puckett SD, Taylor E, Raimondo T, Webster TJ. The relationship between the nanostructure of titanium surfaces and bacterial attachment. Biomaterials. 2010;31(4):706–13.

    Article  CAS  PubMed  Google Scholar 

  72. Neoh KG, Hu X, Zheng D, Kang ET. Balancing osteoblast functions and bacterial adhesion on functionalized titanium surfaces. Biomaterials. 2012;33(10):2813–22.

    Article  CAS  PubMed  Google Scholar 

  73. Linklater DP, Baulin VA, Juodkazis S, Crawford RJ, Stoodley P, Ivanova EP. Mechano-bactericidal actions of nanostructured surfaces. Nat Rev Microbiol. 2020:1–15.

  74. Román-Kustas J, Hoffman JB, Reed JH, Gonsalves AE, Oh J, Li L, et al. Molecular and topographical organization: influence on Cicada wing wettability and bactericidal properties. Adv Mater Interfaces. 2020;7(10):2000112.

    Article  Google Scholar 

  75. Bhadra CM, Truong VK, Pham VT, Al Kobaisi M, Seniutinas G, Wang JY, et al. Antibacterial titanium nano-patterned arrays inspired by dragonfly wings. Sci Rep. 2015;5(1):1–12.

    Article  Google Scholar 

  76. Linklater DP, Nguyen HKD, Bhadra CM, Juodkazis S, Ivanova EP. Influence of nanoscale topology on bactericidal efficiency of black silicon surfaces. Nanotechnology. 2017;28(24):245301.

    Article  PubMed  Google Scholar 

  77. Kim W, Ng JK, Kunitake ME, Conklin BR, Yang P. Interfacing silicon nanowires with mammalian cells. J Am Chem Soc. 2007;129(23):7228–9.

    Article  CAS  PubMed  Google Scholar 

  78. Shalek AK, Robinson JT, Karp ES, Lee JS, Ahn D-R, Yoon M-H, et al. Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells. Proc Natl Acad Sci. 2010;107(5):1870–5.

    Article  CAS  Google Scholar 

  79. Garnett E, Yang P. Light trapping in silicon nanowire solar cells. Nano Lett. 2010;10(3):1082–7.

    Article  CAS  PubMed  Google Scholar 

  80. Anderson JM, Rodriguez A, Chang DT, editors. Foreign body reaction to biomaterials. Semin Immunol. 2008; Elsevier.

  81. Zimmerli W, Sendi P, editors. Pathogenesis of implant-associated infection: the role of the host. Semin Immunopathol 2011; Springer.

  82. Kristian SA, Birkenstock TA, Sauder U, Mack D, Götz F, Landmann R. Biofilm formation induces C3a release and protects Staphylococcus epidermidis from IgG and complement deposition and from neutrophil-dependent killing. J Infect Dis. 2008;197(7):1028–35.

    Article  PubMed  Google Scholar 

  83. Zimmerli W, Waldvogel FA, Vaudaux P, Nydegger UE. Pathogenesis of foreign body infection: description and characteristics of an animal model. J Infect Dis. 1982;146(4):487–97.

    Article  CAS  Google Scholar 

  84. Selders GS, Fetz AE, Radic MZ, Bowlin GL. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen Biomater. 2017;4(1):55–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Sekizuka E, Grisham MB, Li M, Deitch EA, Granger DN. Inflammation-induced intestinal hyperemia in the rat: role of neutrophils. Gastroenterology. 1988;95(6):1528–34.

    Article  CAS  PubMed  Google Scholar 

  86. Lawrence DW, Pryzwansky KB. The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading. J Immunol. 2001;166(9):5550–6.

    Article  CAS  PubMed  Google Scholar 

  87. Weber M, Steinle H, Golombek S, Hann L, Schlensak C, Wendel HP, et al. Blood-contacting biomaterials: in vitro evaluation of the hemocompatibility. Front Bioeng Biotechnol. 2018;6:99.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Mariani E, Lisignoli G, Borzì RM, Pulsatelli L. Biomaterials: foreign bodies or tuners for the immune response? Int J Mol Sci. 2019;20(3):636.

    Article  CAS  PubMed Central  Google Scholar 

  89. Jhunjhunwala S, Aresta-DaSilva S, Tang K, Alvarez D, Webber MJ, Tang BC, et al. Neutrophil responses to sterile implant materials. PloS one. 2015;10(9):e0137550.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Cohen HC, Lieberthal TJ, Kao WJ. Poly (ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes. J Biomed Mater Res Part A. 2014;102(12):4252–61.

    PubMed  PubMed Central  Google Scholar 

  91. Novak ML, Koh TJ. Phenotypic transitions of macrophages orchestrate tissue repair. Am J Pathol. 2013;183(5):1352–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44(3):450–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gonzalez-Simon AL, Eniola-Adefeso O. Host response to biomaterials. Eng Biomater Regen Med Springer 2012; p. 143–59.

    Google Scholar 

  94. Badolato R, Ponzi AN, Millesimo M, Notarangelo LD, Musso T. Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes. Blood, J Am Soc Hematol. 1997;90(7):2804–9.

    CAS  Google Scholar 

  95. Hazuda D, Lee J, Young P. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem. 1988;263(17):8473–9.

  96. Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain. 2006;129(1):200–11.

    Article  PubMed  Google Scholar 

  97. Müller E, Christopoulos PF, Halder S, Lunde A, Beraki K, Speth M, et al. Toll-like receptor ligands and interferon-γ synergize for induction of antitumor M1 macrophages. Front Immunol. 2017;8:1383.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarization. Front Biosci. 2008;13(1):453–61.

    Article  CAS  PubMed  Google Scholar 

  99. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Rodell CB, Arlauckas SP, Cuccarese MF, Garris CS, Li R, Ahmed MS, et al. TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. Nat Biomed Eng. 2018;2(8):578–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Vinod N, Hwang D, Azam SH, Van Swearingen AE, Wayne E, Fussell SC, et al. High-capacity poly (2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma. Sci Adv. 2020;6(25):eaba5542.

  102. Keeler GD, Durdik JM, Stenken JA. Localized delivery of dexamethasone-21-phosphate via microdialysis implants in rat induces M (GC) macrophage polarization and alters CCL2 concentrations. Acta Biomater. 2015;12:11–20.

    Article  CAS  PubMed  Google Scholar 

  103. Doloff JC, Veiseh O, Vegas AJ, Tam HH, Farah S, Ma M, et al. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat Mater. 2017;16(6):671–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Chung L, Maestas D, Lebid A, Mageau A, Rosson GD, Wu X, et al. Interleukin-17 and senescence regulate the foreign body response. BioRxiv. 2019;583–757.

  105. Sommerfeld SD, Cherry C, Schwab RM, Chung L, Maestas DR, Laffont P, et al. Interleukin-36γ–producing macrophages drive IL-17–mediated fibrosis. Sci Immunol. 2019;4(40):eaax4783.

  106. Wolfram D, Rabensteiner E, Grundtman C, Böck G, Mayerl C, Parson W, et al. T regulatory cells and TH17 cells in peri–silicone implant capsular fibrosis. Plast Reconstr Surg. 2012;129(2):327e–37e.

    Article  CAS  PubMed  Google Scholar 

  107. Barin JG, Baldeviano GC, Talor MV, Wu L, Ong S, Quader F, et al. Macrophages participate in IL-17-mediated inflammation. Eur J Immunol. 2012;42(3):726–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Chung L, Maestas DR, Lebid A, Mageau A, Rosson GD, Wu X, et al. Interleukin 17 and senescent cells regulate the foreign body response to synthetic material implants in mice and humans. Sci Transl Med. 2020;12(539).

  109. Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301.

    PubMed  PubMed Central  Google Scholar 

  110. Hannan RT, Peirce SM, Barker TH. Fibroblasts: diverse cells critical to biomaterials integration. ACS Biomater Sci Eng. 2017;4(4):1223–32.

    Article  Google Scholar 

  111. Rognoni E, Pisco AO, Hiratsuka T, Sipilä KH, Belmonte JM, Mobasseri SA, et al. Fibroblast state switching orchestrates dermal maturation and wound healing. Mol Sys Biol. 2018;14(8):e8174.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Van Linthout S, Miteva K, Tschöpe C. Crosstalk between fibroblasts and inflammatory cells. Cardiovasc Res. 2014;102(2):258–69.

    Article  PubMed  Google Scholar 

  113. Klingberg F, Hinz B, White ES. The myofibroblast matrix: implications for tissue repair and fibrosis. Journal Pathol. 2013;229(2):298–309.

    Article  CAS  PubMed  Google Scholar 

  114. Phan SH. The myofibroblast in pulmonary fibrosis. Chest. 2002;122(6):286S-9S.

    Article  PubMed  Google Scholar 

  115. Pitha I, Oglesby E, Chow A, Kimball E, Pease ME, Schaub J, et al. Rho-kinase inhibition reduces myofibroblast differentiation and proliferation of scleral fibroblasts induced by transforming growth factor β and experimental glaucoma. Transl Vis Sci Technol. 2018;7(6):6.

  116. Veiseh O, Doloff JC, Ma M, Vegas AJ, Tam HH, Bader AR, et al. Size-and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater. 2015;14(6):643–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Sadtler K, Estrellas K, Allen BW, Wolf MT, Fan H, Tam AJ, et al. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. Science. 2016;352(6283):366–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. McWhorter FY, Wang T, Nguyen P, Chung T, Liu WF. Modulation of macrophage phenotype by cell shape. Proc Natl Acad Sci. 2013;110(43):17253–8.

    Article  CAS  Google Scholar 

  119. Tylek T, Blum C, Hrynevich A, Schlegelmilch K, Schilling T, Dalton PD, et al. Precisely defined fiber scaffolds with 40 μm porosity induce elongation driven M2-like polarization of human macrophages. Biofabrication. 2020;12(2):025007.

    Article  CAS  PubMed  Google Scholar 

  120. Li X, Cho B, Martin R, Seu M, Zhang C, Zhou Z, et al. Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction. Sci Transl Med. 2019;11(490).

  121. Wolf MT, Daly KA, Brennan-Pierce EP, Johnson SA, Carruthers CA, D’Amore A, et al. A hydrogel derived from decellularized dermal extracellular matrix. Biomaterials. 2012;33(29):7028–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Jagannathan R, Patel SA, Ali MK, Narayan KV. Global updates on cardiovascular disease mortality trends and attribution of traditional risk factors. Curr Diab Rep. 2019;19(7):44.

    Article  PubMed  Google Scholar 

  123. Secretariat MA. Stenting for peripheral artery disease of the lower extremities: an evidence-based analysis. Ont Health technol Assess Ser. 2010;10(18):1.

    Google Scholar 

  124. Chen D, Jepson N. Coronary stent technology: a narrative review. Med J Aus. 2016;205(6):277–81.

    Article  PubMed  Google Scholar 

  125. Simard T, Hibbert B, Ramirez FD, Froeschl M, Chen Y-X, O’Brien ER. The evolution of coronary stents: a brief review. Can J Cardiol. 2014;30(1):35–45.

    Article  Google Scholar 

  126. Meraj PM, Jauhar R, Singh A. Bare metal stents versus drug eluting stents: where do we stand in 2015? Curr Treat Options Cardiovasc Med. 2015;17(8):39.

    Article  Google Scholar 

  127. Iqbal J, Gunn J, Serruys PW. Coronary stents: historical development, current status and future directions. Br Med Bull. 2013;106(1).

  128. Hu Y, Böck G, Wick G, Xu Q. Activation of PDGF receptor α in vascular smooth muscle cells by mechanical stress. The FASEB Journal. 1998;12(12):1135–42.

    Article  CAS  PubMed  Google Scholar 

  129. Scott NA. Restenosis following implantation of bare metal coronary stents: pathophysiology and pathways involved in the vascular response to injury. Adv Drug Deliv Rev. 2006;58(3):358–76.

    Article  CAS  PubMed  Google Scholar 

  130. Inoue T, Croce K, Morooka T, Sakuma M, Node K, Simon DI. Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis. JACC: Cardiovasc Interv. 2011;4(10):1057–66.

  131. Shen H, Dai Z, Wang M, Gu S, Xu W, Xu G, et al. Preprocedural neutrophil to albumin ratio predicts in-stent restenosis following carotid angioplasty and stenting. J Stroke Cerebrovasc Dis. 2019;28(9):2442–7.

    Article  PubMed  Google Scholar 

  132. Jamshidi P, Mahmoody K, Erne P. Covered stents: a review. Intern J Cardiol. 2008;130(3):310–8.

    Article  PubMed  Google Scholar 

  133. Stankovic G, Colombo A, Presbitero P, Van den Branden F, Inglese L, Cernigliaro C, et al. Randomized evaluation of polytetrafluoroethylene-covered stent in saphenous vein grafts: the Randomized Evaluation of polytetrafluoroethylene COVERed stent in Saphenous vein grafts (RECOVERS) Trial Circulation. 2003;108(1):37–42.

    Article  CAS  PubMed  Google Scholar 

  134. Oh B, Lee CH. Advanced cardiovascular stent coated with nanofiber. Mol Pharm. 2013;10(12):4432–42.

    Article  CAS  PubMed  Google Scholar 

  135. Halkin A, Stone GW. Polymer-based paclitaxel-eluting stents in percutaneous coronary intervention: a review of the TAXUS Trials. Journal of interventional cardiology. 2004;17(5):271–82.

    Article  PubMed  Google Scholar 

  136. Kereiakes DJ, Choo JK, Young JJ, Broderick TM. Thrombosis and drug-eluting stents: a critical appraisal. Rev Cardiovasc Med. 2004;5(1):9–15.

    PubMed  Google Scholar 

  137. Bharadwaj P, Chadha D. Drug eluting stents: To evolve or dissolve? Med J Armed Forces India. 2016;72(4):367–72.

  138. Maeng M, Jensen LO, Kaltoft A, Hansen HH, Bøttcher M, Lassen JF, et al. Comparison of stent thrombosis, myocardial infarction, and mortality following drug-eluting versus bare-metal stent coronary intervention in patients with diabetes mellitus. Am J Cardiol. 2008;102(2):165–72.

    Article  CAS  PubMed  Google Scholar 

  139. Wendel HP, Avci-Adali M, Ziemer G. Endothelial progenitor cell capture stents—hype or hope? Intern J Cardiol. 2010;145(1):115–7.

    Article  PubMed  Google Scholar 

  140. Haude M, Lee SW, Worthley SG, Silber S, Verheye S, Erbs S, et al. The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent. JACC: Cardiovasc Interv. 2013;6(4):334–43.

Download references

Acknowledgements

BioRender was used to create Figs. 1 and 3.

Funding

This work was supported by the National Institutes of Health (R01HL141612), the Department of Defense Vision Research Program (W81XWH2010922), the Robert H. Smith Family Foundation, the KKESH-WEI Collaborative Research Fund, and an unrestricted grant from Research to Prevent Blindness to the Wilmer Eye Institute.

Author information

Authors and Affiliations

  1. Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA

    Aditya Josyula, Kunal S. Parikh, Ian Pitha & Laura M. Ensign

  2. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA

    Aditya Josyula & Laura M. Ensign

  3. Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Kunal S. Parikh, Ian Pitha & Laura M. Ensign

  4. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA

    Kunal S. Parikh & Laura M. Ensign

  5. Center for Bioengineering Innovation and Design, Johns Hopkins University, Baltimore, MD, 21218, USA

    Kunal S. Parikh

  6. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Laura M. Ensign

  7. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, 21287, USA

    Laura M. Ensign

  8. Departments Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Laura M. Ensign

  9. Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Laura M. Ensign

Authors
  1. Aditya Josyula
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kunal S. Parikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ian Pitha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laura M. Ensign
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the manuscript and have read and approved the submitted version.

Corresponding author

Correspondence to Laura M. Ensign.

Ethics declarations

Consent for publication

All authors provide their consent for publication.

Competing interests

K.S.P. and L.M.E. are inventors on patent applications related to electrospinning approaches for producing drug-eluting sutures. All other authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Josyula, A., Parikh, K.S., Pitha, I. et al. Engineering biomaterials to prevent post-operative infection and fibrosis. Drug Deliv. and Transl. Res. 11, 1675–1688 (2021). https://doi.org/10.1007/s13346-021-00955-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-021-00955-0

Keywords

Search

Navigation