Contents lists available at ScienceDirect Journal of Non-Crystalline Solids journal homepage: www.elsevier.com/locate/jnoncrysol Nano and microstructure of bioglasses: In vitro and in vivo bioactivity properties H. Algarni a,b , Ibrahim AlShahrani c,d , Essam H. Ibrahim e,f , Refaat A. Eid g , Mona Kilany h,i , Hamed A. Ghramh a,e , Essam R. Shaaban j , M. Reben k , El Sayed Yousef a,b,j, ⁎ a Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha 61413, P. O. Box 9004, Saudi Arabia b Physics Dep., Faculty of Science, King Khalid University, P. O. Box 9004, Abha, Saudi Arabia c Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Khalid University, Abha, Saudi Arabia d Collaborative Center of Creative Maxillofacial Research and Treatment Modalities, Abha, Saudi Arabia e Biology Department, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia f Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, Egypt g Department of Pathology, College of Medicine, King Khalid University, PO Box 641, Abha, Saudi Arabia h Biology Department, Faculty of Sciences and Arts, King Khalid University, Dhahran Al Janoub, Saudi Arabia i Department of Microbiology, National Organization for Drug Control and Research (NODCAR), Cairo, Egypt j Physics Department, Faculty of Science, Al-Azhar University, P. O. 71452, Assiut, Egypt k Faculty of Materials Science and Ceramics, AGH – University of Science and Technology, al. Mickiewicza 30, 30-059 Cracow, Poland ARTICLE INFO Keywords: Bioglasses Titanium oxide Antimicrobial activity Cytotoxicity Anticancer activity Hypersensitivity responses ABSTRACT Incorporated titanium oxide to bioglasses with novel composition as: 40P2O5- 20Na2O- 10Ca(OH)2- 20CaCl2–8.0ZnO- 1.0TiO2 (labeled BGTi) was tested for its antimicrobial activity, anti-proliferative/cytotoxicity against normal and activated splenic cells in vitro, anticancer activity, in vivo immunologic and hypersensitivity responses, in vivo and in vitro cytotoxicity effects and in vitro effects of activated splenic cells on BGTi. These results showed that BGTi had antimicrobial activities against Gram negative and positive bacteria as well as fungi. The prepared bioglasses BGTi had no cytotoxic or proliferative effects on activated splenic cells while showed anti-proliferative/cytotoxicity against normal splenic cells. It was cytotoxic to HepG2 cells. In vivo test demonstrated that BGTi is an inert material which did not stimulate the immune system or caused local reac- tions. The products of activated splenic cells did not cause any changes in the structure of BGTi also it did not cause any acute cytotoxicity or lysis to RBCs. TiO2 is an inert material which did not cause immune stimulation or hepatic cytotoxicity. BGTi did not affect by lytic products of immune cells hence, it can be considered as a safe and ideal material for implantation inside the body of living organisms. Finally we investigated the structure of the bioglasses BGTi by using Raman spectra. 1. Introduction Many research shows biomaterials have been the subject of much interest with their vast potential in the tissue engineering applications [1–5]. A number of bioactive glasses have been constructed for the repair of bony tissues. The glasses with composition P 2 O 5 -CaO-Na 2 O is poor chemical durability hence to solve this problem, differently modified metal oxides such as CuO, ZnO, MgO, Al 2 O 3 and Fe 2 O 3 [4–8] have been incorporated into the glasses matrix to control the degrad- ability that can be improved to the medical application. In the present work ZnO and TiO 2 oxide can be used to control and enhancement degradability of meta and poly-phosphate glasses [7–9]. Moreover the titanium oxide is more effective for improving the mechanical proper- ties of these glasses. TiO 2 can create calcium phosphate surface nu- cleation in CaO-P 2 O 5 based system [9–12]. With a high content of TiO 2 in the phosphate glasses leads to increase in increased expression in vitro and increased bone formation in vivo may be seen at the highest TiO 2 content. Formation Ti-O-P rather P-O-P bonds lead to stabilize the phosphate glasses matrix [13–20] and also Ti 4+ ions being released actually play a biological role. Hence thus in the present work the effect of TiO 2 incorporation on the P 2 O 5 - Na 2 O- Ca(OH) 2 - CaCl 2 - ZnO glasses matrix has been evaluated. Moreover, it was assumed that the influence of high phosphate concentration content P 2 O 5 on the bioactivity glasses leads to glasses network connectivity increases in the rate of formation https://doi.org/10.1016/j.jnoncrysol.2019.02.018 Received 7 December 2018; Received in revised form 8 February 2019; Accepted 14 February 2019 ⁎ Corresponding author at: Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha 61413, P. O. Box 9004, Saudi Arabia. E-mail address: omn_yousef2000@yahoo.com (E.S. Yousef). Journal of Non-Crystalline Solids 512 (2019) 72–80 0022-3093/ © 2019 Elsevier B.V. All rights reserved. T