ORIGINAL ARTICLE Guaiacol/β-cyclodextrin for rapid healing of dry socket: antibacterial activity, cytotoxicity, and bone repair—an animal study Patricia Verónica Aulestia-Viera 1 & Sávio Morato Lacerda Gontijo 2 & Alinne Damásia Martins Gomes 3 & Rubén Dario Sinisterra 3 & Rodney Garcia Rocha 1 & Maria Esperanza Cortés 2 & Marinilce Fagundes dos Santos 4 & Maria Aparecida Borsatti 1 Received: 26 September 2018 /Accepted: 29 January 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 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. Keywords Antibacterial agent . Cytotoxicity . Dry socket . Guaiacol . Oral surgery . Animal study Introduction Tooth extraction is a routine procedure in dentistry, and dry socket is among the most common and symptomatic post- extraction complications [1, 2]. Despite its high incidence, no consensus on the treatment of dry socket has been reached [3, 4], and some proposed protocols have been based on weak scientific evidence [4, 5]. As other phenolics, guaiacol (Gu) has analgesic [6], anti- oxidant [7], and antimicrobial [8, 9] properties. Gu also stim- ulates osteogenesis-related genes [6] and is less cytotoxic than other well-known phenolics, such as eugenol [10, 11]; thus, its use as an alternative treatment for dry socket should be ex- plored. Despite its beneficial properties, Gu is difficult to ma- nipulate and store due to its low stability and high volatility [12, 13]. To improve its properties and increase its clinical applicability, we proposed the formation of an inclusion com- plex of Gu with β-cyclodextrin (βcd). Cyclodextrins are cyclic oligosaccharides used to moderate drugs’ physicochemical characteristics, increasing bioavail- ability and biological activity [14, 15]. Previous studies in- volving Gu/βcd inclusion complex development have fo- cused on its physicochemical characterization [16, 17], and not on its possible clinical uses. To the best of our knowledge, it has never been used in dentistry. * Maria Aparecida Borsatti maborsat@usp.br 1 Department of Stomatology, Faculty of Dentistry, University of São Paulo, Av. Professor Lineu Prestes, 2227, Cidade Universitária, São Paulo, SP 05508-000, Brazil 2 Department of Restorative Dentistry, Faculty of Dentistry, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, MG, Brazil 3 Department of Chemistry, Exact Sciences Institute, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, MG, Brazil 4 Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 1524, Cidade Universitária, São Paulo, SP, Brazil Oral and Maxillofacial Surgery https://doi.org/10.1007/s10006-019-00747-4