Structural and in vitro study of cerium, gallium and zinc containing sol–gel bioactive glasses Shruti Shruti, a Antonio J. Salinas, * bc Gianluca Malavasi, * a Gigliola Lusvardi, a Ledi Menabue, a Chiara Ferrara, d Piercarlo Mustarelli d and Maria Vallet-Reg  ı bc Received 21st March 2012, Accepted 12th May 2012 DOI: 10.1039/c2jm31767b Sol–gel derived glasses comprised of bioactive materials exhibit a high in vitro response, i.e., the capability to form a hydroxycarbonate apatite (HCA) layer that is claimed to be responsible for the bonding between the glass and the host bone. In this paper, the sol–gel bioactive glass 80% SiO 2 –15% CaO–5% P 2 O 5 (B_BG) was modified by adding the biologically relevant elements cerium, gallium and zinc. Structural characterization of the glasses was performed by 29 Si MAS NMR and their in vitro response was investigated by soaking them in simulated body fluid (SBF) for up to 15 days at 37  C. The HCA formation was monitored by XRD, FTIR, SEM-EDS and ICP measurements. Ce 3+ , Ga 3+ , and Zn 2+ can be classified as ‘‘intermediate ions’’. However, 29 Si NMR revealed that Ce 3+ ions have a more marked role of ‘‘modifier ions’’ than Ga 3+ ions, while the behavior of Zn 2+ lies between those of Ce 3+ and Ga 3+ . On the other hand, in spite of the decrease in the in vitro response of B_BG by substitution, the glasses show HCA formation after 15 days of soaking. In addition, an increase in substitution of zinc accelerated the formation of HCA along with the formation of the mixed phase CaZn 2 (PO 4 ) 2 $2H 2 O (scholzite) acting as nucleating agent for HCA. Moreover, the therapeutic effect of optimum Zn released as an ionic dissolution product from Zn-glasses could be beneficial to stimulate osteogenesis. 1. Introduction Third generation bioceramics are materials which are based on the biological aim of stimulating regeneration of living tissues. Sol–gel bioactive glass is one of the first materials studied in this generation and still remains a favorite among the scientific community. Excellent bioactive behavior and biocompatibility 1–8 are the key features exhibited by this material, due to which it finds application in the fields of scaffold preparation, 9,10 drug delivery, 11,12 coating of stainless steel implants, 13 tumor treat- ment, 14 etc. Many advanced bioceramics like mesoporous bioactive glasses 15,16 are based on them as well, as they are useful for encapsulation of proteins. 17 Composition plays a key role in defining the unique features of sol–gel bioactive glass. Their ion dissolution products have been reported to stimulate prolifera- tion of osteoblast cells and upregulation of the expression of a number of genes like IGF-I, gpI30 or MAPK3/ERK1. 18 Furthermore, small amounts of trace elements in the glass network, like magnesium or silver, promoted mechanical stability and antimicrobial properties respectively. 19,20 As well as these, doped elements resulted in functionalization and optimi- zation of drug uptake and release. 21,22 In this regard, another set of elements, i.e., gallium, zinc and cerium have established roles in bone metabolism, and little about them has been explored in the field of bioceramics. According to findings, gallium increases bone calcium content and formation of hydroxycarbonate apatite (HCA) crystals. 23,24 It blocks bone reabsorption by inhibiting osteoclast activity thereby involved in anabolic activity. 25–27 On the other hand, an experimental study performed by M. Yamaguchi and R. Yamaguchi 28 reported the physiological significance of zinc in the regulation of bone growth. Zinc also acts as a potent inhib- itor of osteoclastic reabsorption in vitro. 29 In 2010 Zhang et al. 30 demonstrated the positive in vitro effect of cerium on primary mouse osteoblasts and there is also indication of its role in enamel demineralization reduction. 31 We recently reported new quaternary mesoporous bioactive glasses (MBGs) with composition (80  x)% SiO 2 –15% CaO–5% P 2 O 5 (in mol%) substituted alternatively with xCe 2 O 3 , xGa 2 O 3 or xZnO, using the nonionic surfactant PluronicÒ P123 (BASF) as a structure directing agent and studied their in vitro behavior a Department of Chemistry, University of Modena and Reggio Emilia, Via G. Campi 183, 41125 Modena, Italy. E-mail: gmalavasi@unimo.it b Departamento de Quimica Inorganica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. E-mail: salinas@farm.ucm. es c Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain d Department of Chemistry, University of Pavia and INSTM, Via Taramelli 16, 27100 Pavia, Italy 13698 | J. Mater. Chem., 2012, 22, 13698–13706 This journal is ª The Royal Society of Chemistry 2012 Dynamic Article Links C < Journal of Materials Chemistry Cite this: J. Mater. Chem., 2012, 22, 13698 www.rsc.org/materials PAPER