Isabel Margarida Miranda Salvado

Poly(dimethylsiloxane) (PDMS)–SiO₂–CaO-based hybrid materials prepared by sol–gel have proved to be very promising materials for tissue engineering applications and drug-delivery systems. These hybrids are biocompatible and present osteogenic and bioactive properties supporting osteoblast attachment and bone growth. The incorporation of therapeutic elements in these materials, such as boron (B) and calcium (Ca), was considered in this study as an approach to develop biomaterials capable of stimulating bone regeneration. The main purpose of this work was thus to produce, by sol–gel, bioactive and biocompatible hybrid materials of the PDMS–SiO₂–B₂O₃–CaO system, capable of a controlled Ca and B release. Different compositions with different boron amounts were prepared using the same precursors resulting in different monolithic materials, with distinct structures and microstructures. Structural features were assessed by Fourier transform infrared (FT-IR) spectrometry and solid-state nuclear magnetic resonance (NMR) techniques, which confirmed the presence of hybrid bonds (Si–O–Si) between organic (PDMS) and inorganic phase (tetraethyl orthosilicate (TEOS)), as well as borosiloxane bonds (B–O–Si). From the ¹¹B NMR results, it was found that Ca changes the boron coordination, from trigonal (BO₃) to tetrahedral (BO₄). Scanning electron microscopy (SEM) micrographs and N₂ isotherms showed that the incorporation of boron modifies the material’s microstructure by increasing the macroporosity and decreasing the specific surface area (SSA). In vitro tests in simulated body fluid (SBF) showed the precipitation of a calcium phosphate layer on the material surface and the controlled release of therapeutic ions. The cytocompatibility of the prepared hybrids was studied with bone marrow stromal cells (ST-2 cell line) by analyzing the cell viability and cell density. The results demonstrated that increasing the dilution rate of extraction medium from the hybrids leads to improved cell behavior. The relationship between the in vitro response and the structural and microstructural features of the materials was explored. It was shown that the release of calcium and boron ions, determined by the hybrid structure was crucial for the observed cells behavior. Although not completely understood, the encouraging results obtained constitute an incentive for further studies on this topic.

We show the influence of two functional ions (Cu²⁺ and La³⁺), incorporated into a quaternary (Si, Ca, Na, P) sol‐gel derived bioactive glass system, on its particle size, cytotoxicity, and bioactivity. By doping the parent glass with the two ions in singular or combined forms, 15 doped glasses were prepared by a rapid sol‐gel technique. The influence of the combined doping on the particle size and cell viability was successfully evaluated by the aid of signal‐to‐noise‐ratio (S/N), using Taguchi analysis. This allowed us to analyze the complex interplay of effects between these ions, and the marked differences in biocompatibility between the three cell types studied. Cu addition had a significant effect on reducing the glass particle size, while both increased density. Cell viability was significantly improved for some doping combinations, demonstrating that while combined Cu–La doping was beneficial for biocompatibility with lymphoblasts, individual high‐Cu or low‐La doping was better with fibroblasts, and either high‐Cu or low‐La doping, or certain combined Cu–La combinations, were the optimum for osteoblasts. However, the bioactivity of doped samples was generally similar to that of the parent glass, although both La, and particularly Cu, did appear to aid dissolution of ions when immersed in SBF, act as glass modifiers, and encourage HAp crystallization. The results reveal that potential synergistic benefits can be obtained by combining the effects on the mean particle size, density, cytotoxicity, and bioactivity of the glasses. The greatly improved biocompatibility of some of the doped glasses makes them promising candidates for biomedical applications.

Bioactive glass powders synthesized by solgel are usually porous and exhibit high specific surface areas, conferring them poor ability for scaffolds fabrication using colloidal processing approaches. The difficulties associated with colloidal processing of solgel glass have hindered so far the processing of 3‐D scaffolds by robocasting. This research paper investigates the importance of calcination temperature ( CT ) and balls to powder ratio ( BPR ) used upon wet milling on the maximum achievable solid loading in aqueous media. The effects of CT , BPR , and solid loading on the flow behavior and viscoelastic properties of the suspensions/pastes were evaluated in this preliminary work. The aim is to disclose the sets of experimental variables that are most promising for the formulation of printable inks, and open the way for the future fabrication of porous scaffolds by robocasting and other 3‐D additive manufacturing techniques.

This work investigates the effects of the type and concentration of acid catalysts on the microstructural features of silica‐rich bioactive glasses (75Si–16Ca–5Na–4P, in mol%) synthesized from acetate and nitrate precursor salts, using an innovative rapid sol‐gel method, followed by thermal stabilization at 550°C. The results of XRD, SEM, Fourier Transform Infrared Spectrometer (FTIR) and solid state MAS NMR analysis revealed that the lower degrees of polymerization and network connectivity were found for bioglass powders obtained in the presence of high acid concentrations. A low amount of citric acid gave a polymerization degree similar to that obtained in the absence of any catalyst, but the synthesis time was as short as that found for high acid concentrations. The XRD and FTIR results demonstrated amorphous glass powders free of any nitrate by‐products. The microstructure and degree of polymerization could be modified by changing the type and concentration of acid catalyst, enabling one to tailor the bioactivity of glasses even without changing the starting composition.

Sol‐gel glasses in quaternary silica–sodium–calcium–phosphorous systems have been synthesized using a rotary evaporator for rapid drying without ageing. This novel fast drying method drastically decreases the total drying and ageing time from several weeks to only 1 hour, thus overcoming a serious drawback in sol‐gel preparation procedures for bioglasses. This work investigates the bioactivity behavior of two glasses synthesized by this fast method, with Ca:P ratios of 1.5, and 1.67. X‐ray diffraction (XRD), Inductive coupled plasma, Fourier‐transform infrared, and Raman spectroscopy were used to confirm the bioactivity of the synthesized powders. MAS‐NMR was also used to assess the degree of silica polymerization. The composition with a higher Ca:P = 1.67 ratio showed better bioactivity in comparison to the one with Ca:P = 1.5, which exhibited little bio‐response with up to 4 weeks of immersion in SBF (simulated body fluid). It was also found that an orbital agitation rate of 120 rpm favors the interfacial bio‐mineralization reactions, promoting the formation of a crystalline hydroxyapatite (HAp) layer at the surface of the (Ca:P = 1.67) composition after 2 weeks immersion in SBF. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 510–520, 2018.

Synthesis of sol‐gel glass with incorporation of Na ₂ O is extremely difficult, as such glasses have a great tendency to crystallize. Slow drying and aging over several days or weeks is usually required in sol‐gel preparation procedures. This work reports a fast, novel route for the synthesis of bioglass powders in a considerably shortened period of 1 h. A comparative study of sol‐gel derived glasses made by this novel route using rotary evaporator drying, and a conventional route using oven drying and aging, revealed that the two methods produce stabilized (devitrified) bio‐glasses with virtually identical behavior and properties. Indeed, the rapidly dried powder exhibited slightly enhanced properties that should result in improved bioactivity. Fourier‐transform infrared spectroscopy was used to understand the structures of the synthesized powders, and MAS ‐ NMR was used to look at the degree of polymerization. This innovative, rapid route was successfully demonstrated to produce glass and devitrified glass nanopowders more than one hundred times quicker than the quickest reported standard drying methods.