Skip to main content
SpringerLink
Log in

Salicylic Acid Polymers in Periodontal Tissue Healing

  • Chapter
  • First Online:
Emerging Therapies in Periodontics

Abstract

Salicylic acid (SA) has therapeutic potential based on its anti-inflammatory and antimicrobial properties. A limitation of SA treatment is its short half-life in vivo that can be overcome by the sustained release by incorporation into a polymer backbone resulting in biodegradable salicylic acid-based poly(anhydride-esters) (SAPAE). In addition to slow release for up to 1 month, SAPAE is simple to produce and is an effective low-cost alternative to biologic factors. These properties are useful in promoting bone regeneration, particularly under situations where inflammation is enhanced by systemic conditions such as diabetes. In a rat critical size defect model, SAPAE application with bone grafting material significantly increased bone fill as assessed by micro-computed tomography (CT) and histomorphometry. While there was accelerated bone formation in the normoglycemic group, there was both accelerated and increased bone formation in diabetic rats. The increased bone formation in the diabetic group was tied to a decrease in inflammation during the period of bone formation, an increase in the number of osteoblasts, and a reduction of osteoclasts. The results suggest that SAPAE polymer can be used to accelerate and enhance bone formation in the treatment of periodontal and other craniofacial osseous defects and may be useful for the treatment of peri-implantitis, particularly in diabetic conditions.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
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

Similar content being viewed by others

References

  1. Mahdi JG, Mahdi AJ, Mahdi AJ, Bowen ID. The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential. Cell Prolif. 2006;39:147–55.

    PubMed  PubMed Central  Google Scholar 

  2. Madan RK, Levitt J. A review of toxicity from topical salicylic acid preparations. J Am Acad Dermatol. 2014;70:788–92.

    PubMed  Google Scholar 

  3. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231:232.

    PubMed  Google Scholar 

  4. Amann R, Peskar BA. Anti-inflammatory effects of aspirin and sodium salicylate. Eur J Pharmacol. 2002;447:1–9.

    PubMed  Google Scholar 

  5. Cottrell J, O’Connor JP. Effect of non-steroidal anti-inflammatory drugs on bone healing. Pharmaceuticals. 2010;3:1668–93.

    PubMed  PubMed Central  Google Scholar 

  6. Higgs GA, Salmon JA, Henderson B, Vane JR. Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity. Proc Natl Acad Sci U S A. 1987;84:1417–20.

    PubMed  PubMed Central  Google Scholar 

  7. Mitchell JA, Saunders M, Barnes PJ, Newton R, Belvisi MG. Sodium salicylate inhibits Cyclo-Oxygenase-2 activity independently of transcription factor (nuclear factor κB) activation: role of arachidonic acid. Mol Pharmacol. 1997;51:907.

    PubMed  Google Scholar 

  8. Ping M, Zizhen L, Meng X, Rui J, Weirui L, Xiaohong W, Shen M, Gaimei S. Naturally occurring methyl salicylate glycosides. Mini-Rev Med Chem. 2014;14:56–63.

    Google Scholar 

  9. Rowland M, Riegelman S. Pharmacokinetics of acetylsalicylic acid and salicylic acid after intravenous administration in man. J Pharm Sci. 1968;57:1313–9.

    Google Scholar 

  10. Prudencio A, Schmeltzer RC, Uhrich KE. Effect of linker structure on salicylic acid-derived poly(anhydride−esters). Macromolecules. 2005;38:6895–901.

    PubMed  PubMed Central  Google Scholar 

  11. Faig Jonathan J, Smith K, Moretti A, Yu W, Uhrich Kathryn E. One-pot polymerization syntheses: incorporating bioactives into poly(anhydride-esters). Macromol Chem Phys. 2016;217:1842–50.

    Google Scholar 

  12. Carbone Ashley L, Uhrich Kathryn E. Design and synthesis of fast-degrading poly(anhydride-esters). Macromol Rapid Commun. 2009;30:1021–6.

    PubMed  PubMed Central  Google Scholar 

  13. Whitaker-Brothers K, Uhrich K. Poly(anhydride-ester) fibers: role of copolymer composition on hydrolytic degradation and mechanical properties. J Biomed Mater Res A. 2004;70A:309–18.

    Google Scholar 

  14. Griffin J, Delgado-Rivera R, Meiners S, Uhrich KE. Salicylic acid-derived poly(anhydride-ester) electrospun fibers designed for regenerating the peripheral nervous system. J Biomed Mat Res A. 2011;97:230–42.

    Google Scholar 

  15. Subramanian S, Mitchell A, Yu W, Snyder S, Uhrich K, O'Connor JP. Salicylic acid-based polymers for guided bone regeneration using bone morphogenetic Protein-2. Tissue Eng Part A. 2015;21:2013–24.

    PubMed  PubMed Central  Google Scholar 

  16. Demirdirek B, Uhrich KE. Physically crosslinked salicylate-based poly (N-isopropylacrylamide-co-acrylic acid) hydrogels for protein delivery. J Bioact Compat Polym. 2018;33:224–36.

    Google Scholar 

  17. Demirdirek B, Uhrich KE. Novel salicylic acid-based chemically crosslinked pH-sensitive hydrogels as potential drug delivery systems. Int J Pharm. 2017;528:406–15.

    PubMed  Google Scholar 

  18. Demirdirek B, Uhrich KE. Salicylic acid-based pH-sensitive hydrogels as potential oral insulin delivery systems. J Drug Target. 2015;23:716–24.

    PubMed  Google Scholar 

  19. Ouimet MA, Fogaca R, Snyder SS, Sathaye S, Catalani LH, Pochan DJ, Uhrich KE. Poly(anhydride-ester) and poly(N-vinyl-2-pyrrolidone) blends: salicylic acid-releasing blends with hydrogel-like properties that reduce inflammation. Macromol Biosci. 2015;15:342–50.

    PubMed  Google Scholar 

  20. Yu W, Bien-Aime S, Li J, Zhang L, McCormack ES, Goldberg ID, Narayan P, Uhrich KE. Injectable microspheres for extended delivery of bioactive insulin and salicylic acid. J Bioact Compat Polym. 2015;30:340–6.

    Google Scholar 

  21. Delgado-Rivera R, Rosario-Melendez R, Yu W, Uhrich KE. Biodegradable salicylate-based poly(anhydride-ester) microspheres for controlled insulin delivery. J Biomed Mat Res A. 2014;102:2736–42.

    Google Scholar 

  22. Rosario-Meléndez R, Ouimet M, Uhrich K. Formulation of salicylate-based poly(anhydride-ester) microspheres for short- and long-term salicylic acid delivery. Polym Bull. 2013;70:343–51.

    Google Scholar 

  23. Díez S, Tros de Ilarduya C. Versatility of biodegradable poly(d,l-lactic-co-glycolic acid) microspheres for plasmid DNA delivery. Eur J Pharm Biopharm. 2006;63:188–97.

    PubMed  Google Scholar 

  24. Stebbins ND, Faig JJ, Yu W, Guliyev R, Uhrich KE. Polyactives: controlled and sustained bioactive release via hydrolytic degradation. Biomater Sci. 2015;3:1171–87.

    PubMed  PubMed Central  Google Scholar 

  25. Elgali I, Omar O, Dahlin C, Thomsen P. Guided bone regeneration: materials and biological mechanisms revisited. Eur J Oral Sci. 2017;125:315–37.

    PubMed  PubMed Central  Google Scholar 

  26. Simon AM, Manigrasso MB, O'Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res. 2002;17:963–76.

    PubMed  Google Scholar 

  27. Sri B, Vadithya A, Chatterjee A. As a review on hydrogels as drug delivery in the pharmaceutical field. Int J Pharm Chem Sci. 2012;1:642–61.

    Google Scholar 

  28. Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J. Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng. 2000;2:9–29.

    PubMed  Google Scholar 

  29. Lopérgolo LC, Lugão AB, Catalani LH. Direct UV photocrosslinking of poly(N-vinyl-2-pyrrolidone) (PVP) to produce hydrogels. Polymer. 2003;44:6217–22.

    Google Scholar 

  30. Lin C-C, Metters AT. Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Deliv Rev. 2006;58:1379–408.

    PubMed  Google Scholar 

  31. Park H, Park K. Hydrogels in bioapplications. In: Hydrogels and Biodegradable Polymers for Bioapplications. Washington, DC: American Chemical Society; 1996. p. 2–10.

    Google Scholar 

  32. Kipper MJ, Shen E, Determan A, Narasimhan B. Design of an injectable system based on bioerodible polyanhydride microspheres for sustained drug delivery. Biomaterials. 2002;23:4405–12.

    PubMed  Google Scholar 

  33. Whitaker-Brothers K, Uhrich K. Investigation into the erosion mechanism of salicylate-based poly(anhydride-esters). J Biomed Mat Res A. 2006;76:470–9.

    Google Scholar 

  34. Keith CT, Borisy AA, Stockwell BR. Multicomponent therapeutics for networked systems. Nat Rev Drug Discov. 2005;4:71.

    PubMed  Google Scholar 

  35. Kumar CG, Anand SK. Significance of microbial biofilms in food industry: a review. Int J Food Microbiol. 1998;42:9–27.

    PubMed  Google Scholar 

  36. Perilli R, Marziano ML, Formisano G, Caiazza S, Scorcia G, Baldassarri L. Alteration of organized structure of biofilm formed by Staphylococcus epidermidis on soft contact lenses. J Biomed Mater Res. 2000;49:53–7.

    PubMed  Google Scholar 

  37. Phan TN, Reidmiller JS, Marquis RE. Sensitization of actinomyces naeslundii and streptococcus sanguis biofilms and suspensons to acid damage by fluoride and other weak acids. Arch Microbiol. 2000;174(4):248–55.

    PubMed  Google Scholar 

  38. Muller E, Al-Attar J, Wolff AG, Farber BF. Mechanism of salicylate-mediated inhibition of biofilm in Staphylococcus epidermidis. J Infect Dis. 1998;177:501–3.

    PubMed  Google Scholar 

  39. Brown MRW, Allison DG, Gilbert P. Resistance of bacterial biofilms to antibiotics a growth-rate related effect? J Antimicrob Chemother. 1988;22:777–80.

    PubMed  Google Scholar 

  40. Dunne WM Jr, Mason EO Jr, Kaplan SL. Diffusion of rifampin and vancomycin through a Staphylococcus epidermidis biofilm. Antimicrob Agents Chemother. 1993;37:2522–6.

    PubMed  PubMed Central  Google Scholar 

  41. Arciola C, Montanaro L, Caramazza R, Sassoli V, Cavedagna D. Inhibition of bacterial adherence to a high-water-content polymer by a water-soluble, nonsteroidal, anti-inflammatory drug. J Biomed Mater Res. 1998;42(1):1–5.

    PubMed  Google Scholar 

  42. 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;27:5039–48.

    PubMed  PubMed Central  Google Scholar 

  43. Rosenberg L, Carbone A, Römling U, Uhrich K, Chikindas M. Salicylic acid-based poly (anhydride esters) for control of biofilm formation in Salmonella enterica serovar typhimurium. Lett Appl Microbiol. 2008;46:593–9.

    PubMed  Google Scholar 

  44. Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB J. 1987;1:89–96.

    PubMed  Google Scholar 

  45. Erdmann L, Macedo B, Uhrich K. Degradable poly (anhydride ester) implants: effects of localized salicylic acid release on bone. Biomaterials. 2000;21:2507–12.

    PubMed  Google Scholar 

  46. Mitchell A, Kim B, Cottrell J, Snyder S, Witek L, Ricci J, Uhrich KE, O’Connor JP. Development of a guided bone regeneration device using salicylic acid-poly(anhydride-ester) polymers and osteoconductive scaffolds. J Biomed Mat Res A. 2014;102:655–64.

    Google Scholar 

  47. Mitchell A, Kim B, Snyder S, Subramanian S, Uhrich K, O’Connor JP. Use of salicylic acid polymers and bone morphogenetic protein-2 to promote bone regeneration in rabbit parietal bone defects. J Bioact Compat Polym. 2015;31:140–51.

    Google Scholar 

  48. Yunus Basha R, Sampath Kumar TS, Doble M. Design of biocomposite materials for bone tissue regeneration. Mater Sci Eng C. 2015;57:452–63.

    Google Scholar 

  49. Dorj B, Won J-E, Purevdorj O, Patel KD, Kim J-H, Lee E-J, Kim H-W. A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery. Acta Biomater. 2014;10:1238–50.

    PubMed  Google Scholar 

  50. Quinlan E, Thompson EM, Matsiko A, O’Brien FJ, López-Noriega A. Functionalization of a collagen–hydroxyapatite scaffold with osteostatin to facilitate enhanced bone regeneration. Adv Healthc Mater. 2015;4:2649–56.

    PubMed  Google Scholar 

  51. Sutherland AJ, Detamore MS. Bioactive microsphere-based scaffolds containing decellularized cartilage. Macromol Biosci. 2015;15:979–89.

    PubMed  PubMed Central  Google Scholar 

  52. Kim B-S, Kim J-S, Yang S-S, Kim H-W, Lim HJ, Lee J. Angiogenin-loaded fibrin/bone powder composite scaffold for vascularized bone regeneration. Biomat Res. 2015;19:18.

    Google Scholar 

  53. Retzepi M, Lewis MP, Donos N. Effect of diabetes and metabolic control on de novo bone formation following guided bone regeneration. Clin Oral Implants Res. 2010;21:71–9.

    PubMed  Google Scholar 

  54. Ramanujam CL, Facaros Z, Zgonis T. An overview of bone grafting techniques for the diabetic charcot foot and ankle. Clin Podiatr Med Surg. 2012;29:589.

    PubMed  Google Scholar 

  55. Wada K, Yu W, Elazizi M, Barakat S, Ouimet MA, Rosario-Meléndez R, Fiorellini JP, Graves DT, Uhrich KE. Locally delivered salicylic acid from a poly(anhydride-ester) impact on diabetic bone regeneration. J Control Release. 2013;171:33–7.

    PubMed  PubMed Central  Google Scholar 

  56. Yu W, Bien-Aime S, Mattos M, Alsadun S, Wada K, Rogado S, Fiorellini J, Graves D, Uhrich K. Sustained, localized salicylic acid delivery enhances diabetic bone regeneration via prolonged mitigation of inflammation. J Biomed Mat Res A. 2016;104:2595–603.

    Google Scholar 

  57. Liu R, Bal HS, Desta T, Behl Y, Graves DT. Tumor necrosis factor-alpha mediates diabetes-enhanced apoptosis of matrix-producing cells and impairs diabetic healing. Am J Pathol. 2006;168:757–64.

    PubMed  PubMed Central  Google Scholar 

  58. Pacios S, Andriankaja O, Kang J, Alnammary M, Bae J, de Brito Bezerra B, Schreiner H, Fine DH, Graves DT. Bacterial infection increases periodontal bone loss in diabetic rats through enhanced apoptosis. Am J Pathol. 2013;183:1928–35.

    PubMed  PubMed Central  Google Scholar 

  59. Xiao W, Li S, Pacios S, Wang Y, Graves DT. Bone remodeling under pathological conditions. Front Oral Biol. 2016;18:17–27.

    PubMed  Google Scholar 

  60. Pacios S, Kang J, Galicia J, Gluck K, Patel H, Ovaydi-Mandel A, Petrov S, Alawi F, Graves DT. Diabetes aggravates periodontitis by limiting repair through enhanced inflammation. FASEB J. 2012;26:1423–30.

    PubMed  PubMed Central  Google Scholar 

  61. Liu R, Bal HS, Desta T, Krothapalli N, Alyassi M, Luan Q, Graves DT. Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation. J Dent Res. 2006;85:510–4.

    PubMed  PubMed Central  Google Scholar 

  62. Kang J, de Brito Bezerra B, Pacios S, Andriankaja O, Li Y, Tsiagbe V, Schreiner H, Fine DH, Graves DT. Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3-dependent mechanism in experimental periodontitis. Infect Immun. 2012;80:2247–56.

    PubMed  PubMed Central  Google Scholar 

  63. Simmons DJ. Fracture healing perspectives. Clin Orthop Relat Res. 1985;200:100–13.

    Google Scholar 

  64. Zhang X, Kohli M, Zhou Q, Graves DT, Amar S. Short- and long-term effects of IL-1 and TNF antagonists on periodontal wound healing. J Immunol. 2004;173:3514–23.

    PubMed  Google Scholar 

  65. Panda H. Handbook on drugs from natrual sources. New Delhi: Asia Pacific Business Press Inc.; 2010.

    Google Scholar 

  66. Mountziaris PM, Mikos AG. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng Part B Rev. 2008;14:179–86.

    PubMed  PubMed Central  Google Scholar 

  67. Mountziaris PM, Spicer PP, Kasper FK, Mikos AG. Harnessing and modulating inflammation in strategies for bone regeneration. Tissue Eng Part B Rev. 2011;17:393–402.

    PubMed  PubMed Central  Google Scholar 

  68. Brugger OE, Bornstein MM, Kuchler U, Janner SF, Chappuis V, Buser D. Implant therapy in a surgical specialty clinic: an analysis of patients, indications, surgical procedures, risk factors, and early failures. Int J Oral Maxillofac Implants. 2015;30:151–60.

    PubMed  Google Scholar 

  69. Claffey N, Clarke E, Polyzois I, Renvert S. Surgical treatment of peri-implantitis. J Clin Periodontol. 2008;35:316–32.

    PubMed  Google Scholar 

  70. Schwarz F, Jepsen S, Herten M, Sager M, Rothamel D, Becker J. Influence of different treatment approaches on non-submerged and submerged healing of ligature induced peri-implantitis lesions: an experimental study in dogs. J Clin Periodontol. 2006;33:584–95.

    PubMed  Google Scholar 

  71. Derks J, Schaller D, Hakansson J, Wennstrom JL, Tomasi C, Berglundh T. Effectiveness of implant therapy analyzed in a Swedish population: prevalence of peri-implantitis. J Dent Res. 2016;95:43–9.

    PubMed  Google Scholar 

  72. Tarnow DP. Increasing prevalence of peri-implantitis: how will we manage? J Dent Res. 2016;95:7–8.

    PubMed  Google Scholar 

  73. Sanz M, Chapple IL, V. E. W. o. P. Working Group 4 of the. Clinical research on peri-implant diseases: consensus report of working group 4. J Clin Periodontol. 2012;39(Suppl 12):202–6.

    PubMed  Google Scholar 

  74. Mellado Valero A, Ferrer García JC, Herrera Ballester A, Labaig Rueda C. Effects of diabetes on the osseointegration of dental implants. Med Oral Patol Oral Cir Bucal (Internet). 2007;12:38–43.

    Google Scholar 

  75. Camargo WA, de Vries R, van Luijk J, Hoekstra JW, Bronkhorst EM, Jansen JA, van den Beucken JJ. Diabetes mellitus and bone regeneration: a systematic review and meta-analysis of animal studies. Tissue Eng Part B Rev. 2017;23:471–9.

    PubMed  Google Scholar 

  76. Genuth S, Alberti K, Bennett P, Buse J, DeFronzo R, Kahn R, Kitzmiller J, Knowler WC, Lebovitz H, Lernmark A. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26:3160–8.

    PubMed  Google Scholar 

  77. Chrcanovic BR, Albrektsson T, Wennerberg A. Diabetes and oral implant failure: a systematic review. J Dent Res. 2014;93:859–67.

    PubMed  PubMed Central  Google Scholar 

  78. Oates TW, Dowell S, Robinson M, McMahan CA. Glycemic control and implant stabilization in type 2 diabetes mellitus. J Dent Res. 2009;88:367–71.

    PubMed  PubMed Central  Google Scholar 

  79. von Wilmowsky C, Stockmann P, Harsch I, Amann K, Metzler P, Lutz R, Moest T, Neukam FW, Schlegel KA. Diabetes mellitus negatively affects peri-implant bone formation in the diabetic domestic pig. J Clin Periodontol. 2011;38:771–9.

    Google Scholar 

  80. Coelho PG, Pippenger B, Tovar N, Koopmans SJ, Plana NM, Graves DT, Engebretson S, van Beusekom HMM, Oliveira P, Dard M. Effect of obesity or metabolic syndrome and diabetes on osseointegration of dental implants in a miniature swine model: a pilot study. J Oral Maxillofac Surg. 2018;76:1677–87.

    PubMed  PubMed Central  Google Scholar 

  81. Abduljabbar T, Al-Sahaly F, Kellesarian SV, Kellesarian TV, Al-Anazi M, Al-Khathami M, Javed F, Vohra F. Comparison of peri-implant clinical and radiographic inflammatory parameters and whole salivary destructive inflammatory cytokine profile among obese and non-obese men. Cytokine. 2016;88:51–6.

    PubMed  Google Scholar 

  82. Daubert DM, Weinstein BF, Bordin S, Leroux BG, Flemming TF. Prevalence and predictive factors for peri-implant disease and implant failure: a cross-sectional analysis. J Periodontol. 2015;86:337–47.

    PubMed  Google Scholar 

  83. Elangovan S, Brogden KA, Dawson DV, Blanchette D, Pagan-Rivera K, Stanford CM, Johnson GK, Recker E, Bowers R, Haynes WG, Avila-Ortiz G. Body fat indices and biomarkers of inflammation: a cross-sectional study with implications for obesity and peri-implant oral health. Int J Oral Maxillofac Implants. 2014;29:1429–34.

    PubMed  Google Scholar 

  84. Vohra F, Alkhudhairy F, Al-Kheraif AA, Akram Z, Javed F. Peri-implant parameters and C-reactive protein levels among patients with different obesity levels. Clin Implant Dent Relat Res. 2018;20:130–6.

    PubMed  Google Scholar 

  85. Li Y, Lu Z, Zhang X, Yu H, Kirkwood KL, Lopes-Virella MF, Huang Y. Metabolic syndrome exacerbates inflammation and bone loss in periodontitis. J Dent Res. 2015;94:362–70.

    PubMed  PubMed Central  Google Scholar 

  86. Wu YY, Xiao E, Graves DT. Diabetes mellitus related bone metabolism and periodontal disease. Int J Oral Sci. 2015;7:63–72.

    PubMed  PubMed Central  Google Scholar 

  87. Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL, Bone IOF, Diabetes Working G. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13:208–19.

    PubMed  Google Scholar 

  88. Graves DT, Alshabab A, Albiero ML, Mattos M, Correa JD, Chen S, Yang Y. Osteocytes play an important role in experimental periodontitis in healthy and diabetic mice through expression of RANKL. J Clin Periodontol. 2018;45:285–92.

    PubMed  PubMed Central  Google Scholar 

  89. Alharbi MA, Zhang C, Lu C, Milovanova TN, Yi L, Ryu JD, Jiao H, Dong G, O'Connor JP, Graves DT. FOXO1 deletion reverses the effect of diabetic-induced impaired fracture healing. Diabetes. 2018;67:2682–94.

    PubMed  PubMed Central  Google Scholar 

  90. Xiao E, Mattos M, Vieira GHA, Chen S, Correa JD, Wu Y, Albiero ML, Bittinger K, Graves DT. Diabetes enhances IL-17 expression and alters the oral microbiome to increase its pathogenicity. Cell Host Microbe. 2017;22:120–128.e124.

    PubMed  PubMed Central  Google Scholar 

  91. Zhou M, Rong R, Munro D, Zhu C, Gao X, Zhang Q, Dong Q. Investigation of the effect of type 2 diabetes mellitus on subgingival plaque microbiota by high-throughput 16S rDNA pyrosequencing. PLoS One. 2013;8:e61516.

    PubMed  PubMed Central  Google Scholar 

  92. Saeb ATM, Al-Rubeaan KA, Aldosary K, Udaya Raja GK, Mani B, Abouelhoda M, Tayeb HT. Relative reduction of biological and phylogenetic diversity of the oral microbiota of diabetes and pre-diabetes patients. Microb Pathog. 2019;128:215–29.

    PubMed  Google Scholar 

  93. Sabharwal A, Ganley K, Miecznikowski JC, Haase EM, Barnes V, Scannapieco FA. The salivary microbiome of diabetic and non-diabetic adults with periodontal disease. J Periodontol. 2019;90:26–34.

    PubMed  Google Scholar 

  94. Ussar S, Fujisaka S, Kahn CR. Interactions between host genetics and gut microbiome in diabetes and metabolic syndrome. Mol Metab. 2016;5:795–803.

    PubMed  PubMed Central  Google Scholar 

  95. Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, Podar M, Leys EJ. Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing. ISME J. 2012;6:1176–85.

    PubMed  Google Scholar 

  96. Mahato N, Wu X, Wang L. Management of peri-implantitis: a systematic review, 2010-2015. Springerplus. 2016;5:105.

    PubMed  PubMed Central  Google Scholar 

  97. Persson LG, Berglundh T, Lindhe J, Sennerby L. Re-osseointegration after treatment of peri-implantitis at different implant surfaces. An experimental study in the dog. Clin Oral Implants Res. 2001;12:595–603.

    PubMed  Google Scholar 

  98. Renvert S, Quirynen M. Risk indicators for peri-implantitis. A narrative review. Clin Oral Implants Res. 2015;26(Suppl 11):15–44.

    PubMed  Google Scholar 

  99. Venza I, Visalli M, Cucinotta M, De Grazia G, Teti D, Venza M. Proinflammatory gene expression at chronic periodontitis and peri-implantitis sites in patients with or without type 2 diabetes. J Periodontol. 2010;81:99–108.

    PubMed  Google Scholar 

  100. Erdmann L, Uhrich K. Synthesis and degradation characteristics of salicylic acid-derived poly (anhydride-esters). Biomaterials. 2000;21:1941–6.

    PubMed  Google Scholar 

  101. Housby JN, Cahill CM, Chu B, Prevelige R, Bickford K, Stevenson MA, Calderwood SK. Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine. 1999;11:347–58.

    PubMed  Google Scholar 

  102. Fujita D, Yamashita N, Iita S, Amano H, Yamada S, Sakamoto K. Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells. Prostaglandins Leukot Essent Fat Acids. 2003;68:351–8.

    Google Scholar 

  103. Gruber R, Karreth F, Fischer M, Watzek G. Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism. Bone. 2002;30:726–32.

    PubMed  Google Scholar 

  104. Lader C, Flanagan A. Prostaglandin E2, interleukin 1α, and tumor necrosis factor-α increase human osteoclast formation and bone resorption in vitro 1. Endocrinology. 1998;139:3157–64.

    PubMed  Google Scholar 

  105. Okada Y, Lorenzo JA, Freeman AM, Tomita M, Morham SG, Raisz LG, Pilbeam CC. Prostaglandin G/H synthase-2 is required for maximal formation of osteoclast-like cells in culture. J Clin Investig. 2000;105:823.

    PubMed  Google Scholar 

  106. Carbone-Howell AL, Stebbins ND, Uhrich KE. Poly(anhydride-esters) comprised exclusively of naturally occurring antimicrobials and EDTA: antioxidant and antibacterial activities. Biomacromolecules. 2014;15:1889–95.

    PubMed  PubMed Central  Google Scholar 

  107. Rosenberg LE, Carbone AL, Romling U, Uhrich KE, Chikindas ML. Salicylic acid-based poly(anhydride esters) for control of biofilm formation in Salmonella enterica serovar typhimurium. Lett Appl Microbiol. 2008;46:593–9.

    PubMed  Google Scholar 

  108. Sanz-Martin I, Doolittle-Hall J, Teles RP, Patel M, Belibasakis GN, Hammerle CHF, Jung RE, Teles FRF. Exploring the microbiome of healthy and diseased peri-implant sites using Illumina sequencing. J Clin Periodontol. 2017;44:1274–84.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Dana Graves

  2. Department of Chemistry, University of California, Riverside, CA, USA

    Yue Cao & Kathryn Uhrich

  3. Department of Biomaterials, New York University College of Dentistry, New York, NY, USA

    Paulo Coelho

  4. Department of Plastic Surgery, New York University School of Medicine, New York, NY, USA

    Paulo Coelho

  5. Department of Biomaterials, New York University College of Dentistry, New York, NY, USA

    Lukasz Witek

Authors
  1. Dana Graves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yue Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paulo Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lukasz Witek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathryn Uhrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dana Graves .

Editor information

Editors and Affiliations

  1. School of Dental Medicine, Department of Periodontics, University of Pennsylvania, Philadelphia, PA, USA

    Sinem Esra Sahingur

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Graves, D., Cao, Y., Coelho, P., Witek, L., Uhrich, K. (2020). Salicylic Acid Polymers in Periodontal Tissue Healing. In: Sahingur, S. (eds) Emerging Therapies in Periodontics. Springer, Cham. https://doi.org/10.1007/978-3-030-42990-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-42990-4_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-42989-8

  • Online ISBN: 978-3-030-42990-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation