# Sintering Behavior of a Six-Oxide Silicate Bioactive Glass for Scaffold Manufacturing
## 1 Introduction  
Among all the available biomaterials optimized up to now for bone regenerative strategies, bioactive glasses (BGs) indeed deserve special attention [1]. The reason for such a keen scientific interest, which is still arising even fifty years after the invention of the first BG composition (Hench's 4555) [2], lies on their high reactivity in physiological environment resulting in tissue-bonding capabilities. It is well known that the precipitation of hydroxyapatite crystals on BG surface [3, 4] allows creating a stable bonding interface between the material and the native tissue and promotes osteointegration processes [5]. In this way, the glass gradually dissolves over time, concurrently with the formation of new, healthy tissue [6]. In clinics, BGs have been widely employed in form of fine powders and particulates, especially in dentistry and orthopedics, where their use is firmly established since many years due to their ability to promote bone remineralization [7], as well as their enormous potential as bioactive coatings on inert metal implants [8, 9, 10]. Recently, the desire to optimize bone tissue engineering strategies for supporting bone regeneration in medium to critically sized defects has shifted the attention toward the optimization of three-dimensional (3D) porous scaffolds able to provide mechanical support and stimulate osteogenic pathways in all those cases in which the physiological self-healing capability of bone appears to be seriously compromised, such as in surgical tumors resection, traumas and congenital diseases [11; 12]. In this regard, the exceptional behavior of BGs in contact with body fluids, as well as the possibility to perform high-temperature treatment to obtain highly densified structures by particles sintering, makes indisputable their enormous potential as basic materials for the production of porous scaffolds for bone tissue engineering application [13]. Moreover, the extreme versatility of BGs allows them to be successfully processed in the form of porous architectures by a wide series of manufacturing techniques, including replication of porous templates [14; 15; 16; 17], foaming methods [18; 19; 20] and, more recently, free-form fabrication strategies, also known under the name of additive manufacturing (AM) technologies [21; 22]. However, despite remarkable technological advances in recent years, the intrinsic brittleness and the low resistance to crack propagation, typical of glass and ceramic materials, still limit the use of BG-based scaffolds in clinical practice, due to the objective difficulty in guaranteeing mechanically reliable structures suitable for a safe usage, especially in load-bearing applications [23]. Apart from the possibility to coat or infiltrate the scaffold with a degradable polymer, which draws inspiration from the natural toughening mechanism of bone [24; 25], one of the most common and easiest strategies to improve the mechanical performances of BG-based scaffolds relies on the material's densification phenomena upon sintering processes [26; 27]. As an example, [PERSON] and coworkers found that increasing the sintering temperature of sol-gel foamed binary scaffolds from 600 to 800 \({}^{\circ}\)C led to an improvement in compressive strength from 0.34 to 2.26 MPa, as a consequence of the thickening of the pore walls and a decrease in textural properties [27]. Most BGs exhibit the tendency to partially crystallize during sintering, thus transforming into glass-ceramic materials [28]. The most famous example is 4555 Bioglass(r), for which the Q\({}^{n}\) (Si) distribution (n = number of bridging oxygens) results in a structure dominated by chains of Q\({}^{2}\) metasilicates that are occasionally cross-linked through Q\({}^{3}\) units, whereas the Q\({}^{1}\) species terminate the chains distribution.