materials Article Sol–Gel Synthesis and Characterization of a Quaternary Bioglass for Bone Regeneration and Tissue Engineering Ricardo Bento 1 , Anuraag Gaddam 1,2 and José M. F. Ferreira 1, *   Citation: Bento, R.; Gaddam, A.; Ferreira, J.M.F. Sol–Gel Synthesis and Characterization of a Quaternary Bioglass for Bone Regeneration and Tissue Engineering. Materials 2021, 14, 4515. https://doi.org/10.3390/ ma14164515 Academic Editor: Gigliola Lusvardi Received: 30 June 2021 Accepted: 4 August 2021 Published: 11 August 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 CICECO—Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal; ricardobento@ua.pt (R.B.); anuraagg@ua.pt (A.G.) 2 Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13566-590, SP, Brazil * Correspondence: jmf@ua.pt; Tel.: +351-234-370-242 Abstract: Sol–gel synthesis using inorganic and/or organic precursors that undergo hydrolysis and condensation at room temperature is a very attractive and less energetic method for preparing bioactive glass (BG) compositions, as an alternative to the melt-quenching process. When properly conducted, sol–gel synthesis might result in amorphous structures, with all of the components intimately mixed at the atomic scale. Moreover, developing new and better performing materials for bone tissue engineering is a growing concern, as the aging of the world’s population leads to lower bone density and osteoporosis. This work describes the sol–gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO 2 –34 CaO–4 MgO–2 P 2 O 5 (mol%), which was prepared using acidified distilled water as a single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The XRD results of samples calcined within the temperature range of 600–900 ◦ C demonstrated that the amorphous nature was maintained until 800 ◦ C, followed by partial crystallization at 900 ◦ C. The specific surface area—an important factor in osteoconduction—was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m 2 /g at 600 ◦ C to 2.2 ± 0.1 m 2 /g at 900 ◦ C, accompanied by consistent changes in average pore size and pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate that the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering. Keywords: bioactive glasses; alkali-free; sol–gel; bone regeneration; tissue engineering 1. Introduction Noticeable increases in life expectancy have been achieved over the past two centuries, as well documented in several literature reports [1,2]. The overall scientific progress made in the medical field, especially over the most recent decades, has greatly contributed to an increase in the population’s quality of life and life expectancy. Such progresses together brought an unavoidable increase in the average age of the population, with social, eco- nomic, and medical consequences [3,4]. Older people are less capable of physical exertion, and the reduction of the mechanical stimuli of the bones, along with the degradation of the tissues due to a lifetime of use, increases the risk of fractures [5,6]. The consequent increased incidence of bone-related diseases (e.g., osteoporosis, trauma fractures, removal of tumours, etc.) challenges researchers to provide new therapeutic solutions to prevent the onset of osteopathy, and to develop bone grafts to treat these ailments. Autografts, although still considered the gold standard due to their optimal osteogenic, osteoinduc- tive, and osteoconductive properties, have multiple drawbacks, including the donor site morbidity and their limited availability [7]. On the other hand, allografts are often asso- ciated with risk of infection and a high non-union rate with host tissue [8,9]. Therefore, Materials 2021, 14, 4515. https://doi.org/10.3390/ma14164515 https://www.mdpi.com/journal/materials