Abstract
Purpose
Dry socket (DS) is one the most common and symptomatic post-extraction complications; however, no consensus on its treatment has been reached. This study aimed to develop a novel dressing material for DS containing the phenolic agent guaiacol and evaluate its biological properties.
Methods
An inclusion complex of guaiacol and β-cyclodextrin (Gu/βcd) was prepared by freeze-drying. Its antibacterial activity over six oral bacteria was analyzed using the microdilution method, and its cytotoxicity in osteoblasts was assessed with the MTT assay. The alveolar healing process induced by Gu/βcd was evaluated histologically after the treatment of DS in rats.
Results
βcd complexation potentiated Gu’s antibacterial effect and reduced its cytotoxicity in osteoblasts. Bone trabeculae were formed in the alveolar apices of rats treated with Gu/βcd by day 7. On day 14, woven bone occupied the apical and middle thirds of the sockets; on day 21, the entire alveolus was filled by newly formed bone, which was in a more advanced stage of repair than the positive control (Alvogyl™).
Conclusion
The improvement in Gu’s biological properties in vitro and the rapid alveolar repair in comparison with Alvogyl™ in vivo demonstrated the benefits of the Gu/βcd complex as a future alternative for the treatment of DS.
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References
Faizel S, Thomas S, Yuvaraj V, Prabhu S, Tripathi G (2015) Comparision between neocone, alvogyl and zinc oxide eugenol packing for the treatment of dry socket: a double blind randomised control trial. J Maxillofac Oral Surg 14:312–320
Gbotolorun OM, Dipo-Fagbemi IM, Olojede AO, Ebigwei S, Adetoye JO (2016) Are systemic antibiotics necessary in the prevention of wound healing complications after intra-alveolar dental extraction? Int J Oral Maxillofac Surg 45:1658–1664
Taberner-Vallverdu M, Nazir M, Sanchez-Garces MA, Gay-Escoda C (2015) Efficacy of different methods used for dry socket management: a systematic review. Med Oral Patol Oral Cir Bucal 20:e633–e639
Kaya GS, Yapici G, Savas Z, Gungormus M (2011) Comparison of alvogyl, SaliCept patch, and low-level laser therapy in the management of alveolar osteitis. J Oral Maxillofac Surg 69:1571–1577
Alexander RE (2000) Dental extraction wound management: a case against medicating postextraction sockets. J Oral Maxillofac Surg 58:538–551
Kato T, Shirayama K, Tsutsui TW, Tsutsui T (2010) Induction of mRNA expression of osteogenesis-related genes by guaiacol in human dental pulp cells. Odontology 98:165–169
Mimura T, Yazaki K, Sawaki K, Ozawa T, Kawaguchi M (2005) Hydroxyl radical scavenging effects of guaiacol used in traditional dental pulp sedation: reaction kinetic study. Biomed Res 26:139–145
Ouwehand A, Tiihonen K, Kettunen H, Peuranen S, Schulze H, Rautonen N (2010) In vitro effects of essential oils on potential pathogens and beneficial members of the normal microbiota. Vet Med 55:71–78
Fitzgerald DJ, Stratford M, Gasson MJ, Narbad A (2005) Structure-function analysis of the vanillin molecule and its antifungal properties. J Agric Food Chem 53:1769–1775
Kobayashi M, Tsutsui TW, Kobayashi T, Ohno M, Higo Y, Inaba T, Tsutsui T (2013) Sensitivity of human dental pulp cells to eighteen chemical agents used for endodontic treatments in dentistry. Odontology 101:43–51
Chang Y-C, Tai K-W, Huang F-M, Huang M-F (2000) Cytotoxic and nongenotoxic effects of phenolic compounds in human pulp cell cultures. J Endod 26:440–443
Kayaci F, Ertas Y, Uyar T (2013) Enhanced thermal stability of eugenol by cyclodextrin inclusion complex encapsulated in electrospun polymeric nanofibers. J Agric Food Chem 61:8156–8165
National Center for Biotechnology Information. PubChem Compound Database; CID=460, https://pubchem.ncbi.nlm.nih.gov/compound/460. Accessed 13 April 2017
Teixeira KI, Denadai AM, Sinisterra RD, Cortes ME (2015) Cyclodextrin modulates the cytotoxic effects of chlorhexidine on microrganisms and cells in vitro. Drug Deliv 22:444–453
Bilia AR, Guccione C, Isacchi B, Righeschi C, Firenzuoli F, Bergonzi MC (2014) Essential oils loaded in nanosystems: a developing strategy for a successful therapeutic approach. Evid Based Complement Alternat Med 2014:651593
Divakar S, Maheswaran M (1997) Structural studies on inclusion compounds of β-cyclodextrin with some substituted phenols. J Incl Phenom 27:113–126
Song LX, Wang HM, Yang Y, Xu P (2007) Preparation and characterization of two solid supramolecular inclusion complexes of guaiacol with β- and γ-cyclodextrin. Bull Chem Soc Jpn 80:2185–2195
Suarez DF, Consuegra J, Trajano VC, Gontijo SM, Guimaraes PP, Cortes ME, Denadai AL, Sinisterra RD (2014) Structural and thermodynamic characterization of doxycycline/beta-cyclodextrin supramolecular complex and its bacterial membrane interactions. Colloids Surf B: Biointerfaces 118:194–201
Schneider HJ, Hacket F, Rüdiger V, Ikeda H (1998) NMR studies of cyclodextrins and cyclodextrin complexes. Chem Rev 98:1755–1785
Kong N, Jiang T, Zhou Z, Fu J (2009) Cytotoxicity of polymerized resin cements on human dental pulp cells in vitro. Dent Mater 25:1371–1375
Clinical Laboratory Standard Institute (2006) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. Seventh Edition. CLSI document M7-A7. 26:14–18
Jullian C, Orosteguis T, Perez-Cruz F, Sanchez P, Mendizabal F, Olea-Azar C (2008) Complexation of morin with three kinds of cyclodextrin. A thermodynamic and reactivity study. Spectrochim Acta A Mol Biomol Spectrosc 71:269–275
Burt S (2004) Essential oils: their antibacterial properties and potential applications in foods--a review. Int J Food Microbiol 94:223–253
Cortés ME, Sinisterra RD, Avila-Campos MJ, Tortamano N, Rocha RG (2001) The chlorhexidine: beta;-cyclodextrin inclusion compound: preparation, characterization and microbiological evaluation. J Incl Phenom Macrocycl Chem 40:297–302
Teixeira KI, Araujo PV, Neves BR, Mahecha GA, Sinisterra RD, Cortes ME (2013) Ultrastructural changes in bacterial membranes induced by nano-assemblies beta-cyclodextrin chlorhexidine: SEM, AFM, and TEM evaluation. Pharm Dev Technol 18:600–608
Hill LE, Gomes C, Taylor TM (2013) Characterization of beta-cyclodextrin inclusion complexes containing essential oils (trans-cinnamaldehyde, eugenol, cinnamon bark, and clove bud extracts) for antimicrobial delivery applications. LWT Food Sci Technol 51:86–93
Imperiale JC, Sosnik AD (2015) Cyclodextrin complexes for treatment improvement in infectious diseases. Nanomedicine (London) 10:1621–1641
Czekanska EM, Stoddart MJ, Richards RG, Hayes JS (2012) In search of an osteoblast cell model for in vitro research. Eur Cell Mater 24:1–17
Haghighat A, Bahri Najafi R, Bazvand M, Badrian H, Khalighinejad N, Goroohi H (2012) The effectiveness of GECB pastille in reducing complications of dry socket syndrome. Int J Dent 2012:587461
Rasheed A, Kumar CKA, Sravanthi VVNSS (2008) Cyclodextrins as drug carrier molecule: a review. Sci Pharm 76:567–598
Sofian ZM, Shafee SS, Abdullah JM, Osman H, Razak SA (2014) Evaluation of the cytotoxicity of levodopa and its complex with hydroxypropyl-ss-cyclodextrin (HP-ss-CD) to an astrocyte cell line. Malays J Med Sci 21:6–11
Rajewski RA, Stella VJ (1996) Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery. J Pharm Sci 85:1142–1169
LaRocca TJ, Pathak P, Chiantia S, Toledo A, Silvius JR, Benach JL, London E (2013) Proving lipid rafts exist: membrane domains in the prokaryote Borrelia burgdorferi have the same properties as eukaryotic lipid rafts. PLoS Pathog 9:e1003353
de Melo Junior EJ, Raposo MJ, Lisboa Neto JA, Diniz MF, Marcelino Junior CA, Sant’Ana AE (2002) Medicinal plants in the healing of dry socket in rats: microbiological and microscopic analysis. Phytomedicine 9:109–116
Cardoso CL, Ferreira Junior O, Carvalho PS, Dionisio TJ, Cestari TM, Garlet GP (2011) Experimental dry socket: microscopic and molecular evaluation of two treatment modalities. Acta Cir Bras 26:365–372
Rodrigues MT, Cardoso CL, Carvalho PS, Cestari TM, Feres M, Garlet GP, Ferreira O Jr (2011) Experimental alveolitis in rats: microbiological, acute phase response and histometric characterization of delayed alveolar healing. J Appl Oral Sci 19:260–268
Merzel J, Salmon CR (2008) Growth and the modeling/remodeling of the alveolar bone of the rat incisor. Anat Rec (Hoboken) 291:827–834
Vieira AE, Repeke CE, Ferreira Junior Sde B, Colavite PM, Biguetti CC, Oliveira RC, Assis GF, Taga R, Trombone AP, Garlet GP (2015) Intramembranous bone healing process subsequent to tooth extraction in mice: micro-computed tomography, histomorphometric and molecular characterization. PLoS One 10:e0128021
Wegenast S (2013) Observe the healing process. Br Dent J 214:217
T Ryalat S, H Al-Shayyab M, Marmash A, A Sawair F, H Baqain Z (2011) The effect of Alvogyl TM when used as a post extraction packing. Jordan J Pharm Sci 4:149–153
Acknowledgements
We acknowledge the National Institute of Science and Technology in Nanobiopharmaceutical, Foundation for Supporting Research in the State of Minas Gerais (FAPEMIG), National Counsel of Technological and Scientific Development (CNPq), and Coordination for the Improvement of Higher Education Personnel (CAPES).
Funding
This work was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil) in the form of a postgraduate scholarship.
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Aulestia-Viera, P.V., Gontijo, S.M.L., Gomes, A.D.M. et al. Guaiacol/β-cyclodextrin for rapid healing of dry socket: antibacterial activity, cytotoxicity, and bone repair—an animal study. Oral Maxillofac Surg 23, 53–61 (2019). https://doi.org/10.1007/s10006-019-00747-4
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DOI: https://doi.org/10.1007/s10006-019-00747-4