1616 Korean J. Chem. Eng., 31(9), 1616-1623 (2014) DOI: 10.1007/s11814-014-0072-9 INVITED REVIEW PAPER pISSN: 0256-1115 eISSN: 1975-7220 INVITED REVIEW PAPER † To whom correspondence should be addressed. E-mail: jbahisamira@yahoo.fr ‡ This authors contributed equally to this work. Copyright by The Korean Institute of Chemical Engineers. Chitosan-based bioglass composite for bone tissue healing : Oxidative stress status and antiosteoporotic performance in a ovariectomized rat model Samira Jebahi* , ** ,† , Hassane Oudadesse*, Gada Ben Saleh***** ,‡ , Mongi Saoudi** ,‡ , Sirrar Mesadhi****, Tarek Rebai****, Hassib Keskes****, Abdelfattah el Feki**, and Hafed el Feki*** *University of Rennes 1, UMR CNRS 6226, Campus de Beaulieu, 263 av. du Général Leclerc, 35042 Rennes, France **Animal Ecophysiology Laboratory, Sfax Faculty of Science, Department of Life Sciences, Sfax, Tunisia ***Science Materials and Environement Laboratory, Sfax Faculty of Science, Sfax, Tunisia ****Histology, Orthopaedic and Traumatology Laboratory Sfax Faculty of Medicine, Sfax, Tunisia *****Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia (Recevied 21 June 2013 • accepted 27 February 2014) Abstract-Tissue engineering has opened up a new therapeutic avenue promising a revolution in regenerative medicine. Considerable attention has been given to chitosan composite materials and their applications in the field of the bone graft substitutes. We evaluated the antioxidative properties of chitosan-doped bioactive glass (BG-CH) with 17 wt% chitosan, and their applications in the guided bone regeneration. BG-CH was produced by a freeze-drying process and implanted in the femoral condyles of ovariectomized rats. Grafted bone tissues were carefully removed to evaluate the oxidative stress analysis, histomorphometric profile and mineral bone distribution by using inductively coupled plasma optical emission spectrometry (ICP-OES). A significant decrease of thiobarbituric acid-reactive substances (TBARs) was observed after BG-CH implantation. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities significantly increased in ovariectomized group implanted with chitosan-doped bioactive glass (OVX- BG-CH) as compared to ovariectomized group implanted with bioactive glass (OVX-BG). The histomorphometric analysis showed that bone/tissue volume (BV/TV), osteoblast number (N.Ob) and osteoblast surface/bone surface (Ob.S/ BS) were significantly higher in OVX-BG-CH group than in OVX-BG group. On the other hand, a rise in Ca and P ion concentrations in the implanted microenvironment was shown to lead to the formation/deposition of Ca-P phases. Trace elements such as Sr and Fe were detected in the newly formed bone and involved in bone healing. These results suggested that BG-CH composites could become clinically useful as a therapeutic and implantable material. Keywords: Chitosan, Bioactive Glass, Graft Biomaterial, Osteoporosis, Antioxidative Profile, Bone Regeneration INTRODUCTION Synthetic bone graft substitutes based on composites consisting of a polymer and a bioactive glass (BG) material are developed in order to achieve successful bone regeneration [1,2]. Once implanted in the bone tissue, BG releases ions such as Na in the glass and begins to exchange with H 3 O + in the biological fluids. The Ca and P are redeposited, leading to the formation of a hydroxyapatite-carbon- ated layer, which is very similar in composition to that of the bone mineral phase and includes organic components such as collagen fibers [3]. Although BG is apparently interesting in terms of bone repair and regeneration, it does not seem optimal in terms of thera- peutic properties. However, chitosan (CH) is widely regarded as a bioactive substance with reactive functional groups [4]. It is a linear copolymer of (1-4) linked 2-acetamido-2-deoxy-d-glucopyranose and 2-amino-2-deoxy-d-glycopyroanose [5]. It is obtained by the deacetylation of its parent polymer chitin, a polysaccharide that is widespread in nature (e.g., crustaceans, insects and certain fungi) [6]. Other multiple functional properties such as drug delivery, antimi- crobial activity and low immunogenicity, have provided ample oppor- tunities for its potential applications [7]. Moreover, CH oral admin- istration is proposed to prevent the decrease in bone mineral den- sity (BMD) by inhibiting osteoclastic cells and preventing bone loss associated with postmenopausal osteoporosis [8]. This bone disor- der can be treated with many bioactive substances such as alendr- onate, which is a bisphosphonate drug [9]. However, when it is as- sociated with the jaw osteonecrosis, this treatment has a rare but serious adverse effect [10]. The association between CH and hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) has recently been extensively described in ovariectomized (OVX) rats [11]. The differentiation and the activity of human pre- osteoclastic cells on Cementek ® material containing 2 % CH (deacety- lation degree: 0.83) (Cementek ® /CH) was compared to the Cementek ® alone. The incorporation of CH to Cementek ® does not affect the proliferation and adhesion of preosteoclasts, but prevents the osteo- clastic resorption of the composite biomaterial. This CH property might positively influence bone formation and bone remodeling in vivo [12]. Likewise, CH+silica membranes were fabricated using a sol-gel process and, thus, osteoblasts were observed to adhere well and grow more actively on such a membrane [13]. CH tolerated the physiological bone formation, healing processes and most impor- tantly enhanced favorably the biochemical responses thanks to its inherent stimulating properties [14]. In addition, the combination of