Mesoporous bioactive scaffolds prepared with cerium-, gallium- and zinc-containing glasses Shruti Shruti a , Antonio J. Salinas b,c,⇑ , Gigliola Lusvardi a , Gianluca Malavasi a,⇑ , Ledi Menabue a , M. Vallet-Regi b,c a Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Via G. Campi 183, 41125 Modena, Italy b Departamento de Quimica Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain c Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain article info Article history: Received 27 May 2012 Received in revised form 12 September 2012 Accepted 19 September 2012 Available online 28 September 2012 Keywords: Scaffolds with hierarchical porosity Mesoporous glasses with Ce 2 O 3 , Ga 2 O 3 or ZnO Rapid prototyping In vitro bioactivity Bone tissue engineering abstract Mesoporous bioactive glass scaffolds (MBG_Scs), based on 80% SiO 2 –15% CaO–5% P 2 O 5 (in mol.%) meso- porous sol–gel glasses substituted with Ce 2 O 3 , Ga 2 O 3 (both 0.2% or 1.0%) and ZnO (0.4% or 2.0%), were synthesized by combination of evaporation-induced self-assembly and rapid prototyping techniques. Cerium, gallium and zinc trace elements were selected because of their inherent beneficial biological properties. Fabricated scaffolds were characterized and compared with unsubstituted scaffold (B_Sc). All of them contained well interconnected ultralarge pores (pores >400 lm) ideal for vascular ingrowth and proliferation of cells. Macropores of size 100–400 lm were present inside the scaffolds. In addition, low-angle X-ray diffraction showed that B_Sc and scaffolds with substituent contents up to 0.4% exhib- ited ordered mesoporosity useful for hosting molecules with biological activity. The textural properties of B_Sc were a surface area of 398 m 2 g 1 , a pore diameter of 4.3 nm and a pore volume of 0.43 cm 3 g 1 .A slight decrease in surface area and pore volume was observed upon substitution with no distinct effect on pore diameter. In addition, all the MBG_Scs except 2.0% ZnO_Sc showed quite quick in vitro bioactive response. Hence, the present study is a positive addition to ongoing research into preparing bone tissue engineering scaffolds from bioceramics containing elements of therapeutic significance. Ó 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Bone regeneration is a natural phenomenon by which new bone is formed during the normal remodeling process, as well as after injury. However, there are certain clinical situations where bone cannot heal itself because the defect is too large or the bone has lost its regenerative capabilities. Bone tissue engineering has emerged as a promising technique in such situations, stimulating regeneration of host bone without posing constraints found in gold standard bone grafting methods [1,2]. It utilizes three-dimensional porous biomaterial scaffolds which act as a temporary framework providing a suitable environment for normal cell growth, and hence helps in tissue regeneration [3]. The success of a synthetic scaffold depends on whether it satis- fies requirements similar to those found in nature for normal bone development. Natural bones possess hierarchical porosity in the range of 1–3500 lm, which is necessary for several physiological functions [4]. Ideally the template must consist of an intercon- nected porous structure with 90% porosity. Pore sizes greater than 100 lm enable cell seeding, tissue ingrowths and vascularisa- tion. Pores in the microporous (<2 nm) or mesoporous (2–50 nm) range promote cell adhesion, adsorption of biological metabolites and resorbability at rates controlled to match that of tissue repair [5–8]. Mesoporous bioactive glass scaffolds have set a mark in the field of bone tissue engineering for exhibiting a well-interconnected macroporous network along with mesopores, enabling them to carry therapeutic drugs [9–12]. Recently, efforts have being made to incorporate elements that have a relevant function and biologi- cal significance in the glass matrix [13–16]. This approach is con- sidered to be economical and stable, as such elements do not pose a risk of decomposition during scaffold manufacture [17]. Recently, the beneficial biological features of cerium, gallium and zinc have prompted scientists to study them in different glass systems [18–22]. Studies have shown that cerium has a positive ef- fect on primary mouse osteoblasts in vitro and cerium oxide nano- particles act as neuroprotective agents [23,24]. In addition, gallium increases bone calcium content, inhibits osteoclast activity and 1742-7061/$ - see front matter Ó 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.actbio.2012.09.024 ⇑ Corresponding authors. Addresses: Departamento de Quimica Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. Tel.: +34 91 394 1861; fax: +34 91 394 1786 (A.J. Salinas), Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Via G. Campi 183, 41125 Modena, Italy. Tel.: +39 0592055041; fax: +39 059373543 (G. Malavasi). E-mail addresses: salinas@farm.ucm.es (A.J. Salinas), gianluca.malavasi@ unimore.it (G. Malavasi). Acta Biomaterialia 9 (2013) 4836–4844 Contents lists available at SciVerse ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat