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CollaboraƟon / Licensing Opportunity HistaƟn-1 improving integraƟon of dental implants x Improved soŌ Ɵssue integraƟon and osseointegraƟon of dental implants based on a cellular response to histaƟn-1 x HistaƟn-1 can be combined with exisƟng techniques to improve integraƟon of implants x Good biocompaƟbility: histaƟn-1 is naturally present in the human body Hista n-1 | so ssue integra on | osseointegra on Background In Vitro Data Hista ns are pep des exclusively present in the saliva of higher primates. They are secreted by the salivary glands and play an important role in protec on of the mouth. Recently we found that one of the hista ns, hista n-1 (Hst1), improves cell-substrate adhesion as well as cell-cell adhesion, sugges ng a role in maintenance of the epithelial architecture and barrier func on. The effect of Hst1 on cell-substrate adhesion is very pronounced, including substrates like glass and tanium. Scien sts from the Academic Medical Center (AMC) and the Academic Centre for Den stry Amsterdam (ACTA) – one of the top 5 dental research ins tutes in the world –showed that Hst1 causes a significant, more than twofold increase in the ability of human adherent cells (oral and non-oral) to a ach and spread, even in condi ons that impair cell spreading. Other tested hista ns do not s mulate cell spreading, indica ng a specific effect of Hst1. Cells treated with Hst1 not only a ach more rapidly, but are also more firmly a ached to a substrate. Titanium is the most commonly used material for dental implants. We have shown improved a achment of several human gingival cell types, treated with Hst1, on tanium with a smooth surface, as well as osteoblast on an SLA-treated tanium surface. Furthermore, we found that canine cells respond in a similar way to Hst1, providing opportuni es for animal tes ng. The Technology Infec on is a common cause for implant failure due to poor adhesion of the implant to so ssues and bone. Hst1 improves a achment of both so ssue cells and bone cells to dental implants by promo ng cell-substrate adhesion, important to seal off the lower part of an implant and thereby prevents infec ons. Moreover, Hst1 may shorten the period between placing the implant and loading it with a replacement tooth. Conven onal techniques to improve so ssue integra on and osseointegra on are based on modifica ons of implant design, surface topography and chemistry. An advantage of the method described here is that it can be combined with existent techniques. Toxic side-effects are not to be expected, since Hst1 is a pep de naturally present in the human body, and we found no nega ve effect of Hst1 on cell survival. Hist1 could be administered by injec on to give a burst release or, alterna vely, techniques are available to have a prolonged, slow release of Hst1. ApplicaƟons Hst1 can be used in combina on with exis ng techniques to improve integra on of dental implants. Hst1 can also be applied to implants or materials placed in other sites in the human body. What are we looking for? Licensing and collabora on partner for this technique to extend the exis ng data set with in vivo data. Our lab has all the exper se and techniques to form a frui ul collabora on. Inventors Dr. Jan Stap – Department of Medical Biology, AMC Irene van Dijk, MSc – Department of Medical Biology, AMC & Department of Oral Biochemistry, ACTA 1 Figure 1: human gingival epithelial cells, fibroblasts and osteoblasts aƩach beƩer to Ɵtanium in the presence of histaƟn-1. (C = control, Hst1 = HistaƟn-1, C pep = Control pepƟde). Right hand side: microscopy images of epithelial cells on Ɵtanium, made visible with an orange fluorescent dye. Figure 2: human gingival epithelial cells, fibroblasts and osteoblasts spread beƩer on Ɵtanium in the presence of histaƟn-1. (C = control, Hst1 = HistaƟn-1, C pep = Control pepƟde). Below: microscopy images of epithelial cells on Ɵtanium, made visible with an orange fluorescent dye. White arrows indicate spreading cells. Key PublicaƟons I.A. van Dijk et al. Hista n 1 enhances cell adhesion to tanium in an implant integra on model. Journal of Dental Research, online publica on Dec 2016 I.A. van Dijk et al. Hista n-1, a his dine-rich pep de in human saliva, promotes cell-substrate and cell-cell adhesion. FASEB Journal, Aug 2015; 29(8):3124-32. For more informaƟon about collaboraƟon opportuniƟes visit the IXA website: h p://www.ixa.nl/en/for-companies.html or contact our office: S.J. Stembert [email protected] or Tel: +31 20 5668022 Contact x Sanne Stembert x +31 20 566 8022 x [email protected] x www.ixa.nl 2