Phosphate/oxyfluorophosphate glass crystallization and its impact on dissolution and cytotoxicity.

The role of fluorine in bioactive glasses is of interest due to the potential of precipitating fluorapatite, a phase with higher chemical resistance than the typical hydroxyapatite precipitated from oxide bioactive glasses. However, the introduction of fluorine in silicate bioactive glasses was found deleterious to the bioactivity of the glass. Here, phosphate glasses with the composition 75NaPO3-(25-x) CaO-xCaF2 (in mol%), with x = 0-20 and glass-ceramics were investigated to evaluate their potential as substitutes to the traditional silicate bioactive glass. An increase in CaF2 substitution for CaO led to an increase in the glass solubility, due to an increase in highly soluble F(M)n species (where M is a cation) and to an increased polymerization of the phosphate network. Structural analysis reveals the formation of FP bonds, in addition to the F(M)n species, in the glass with the higher CaF2 content. Furthermore, with heat treatment, CaF2 crystals precipitate within the bulk in the newly developed glass, when x = 20. This bulk crystallization reduces the glass dissolution without compromising the precipitation of a reactive layer at the glass surface. Finally, in vitro cell tests were performed using MC3T3 pre-osteoblastic cells. While the substitution of CaF2 for CaO led to an increased cytotoxicity, the controlled crystallization of the fluorine containing glasses decreased such cytotoxicity to similar values than traditional bioactive phosphate glass (x0). This study reports on new oxyfluorophosphate glass and glass-ceramics able, not only, to precipitate a Ca-P reactive layer but also to be processed into glass-ceramics with controlled crystal size, density and cellular activity. STATEMENT OF SIGNIFICANCE: Uncontrolled crystallization of bioactive glasses has negative effect on the materials' bioactivity. While in silicate glass the bioactivity is solely reduced, in phosphate glasses it is often completely suppressed. Furthermore, the need for fluorine containing bioactive glasses, not only for use in bone reconstruction but also in toothpaste as emerged. The addition of F in both silicate and phosphate has led to challenges due the lack of Si-F or P-F bonds, generally leading to a decrease in bioactivity. Here, we developed a bioactive invert phosphate glass where up to 20 mol% of CaO was replaced with CaF2. In the new developed glasses, NMR demonstrated formation of P-F bonds. The content of fluorine was tailored to induce CaF2 bulk crystallization. Overall an increase in F was associated with an increase network connectivity. In turns it led to an increased dissolution rate which was linked to a higher cytotoxicity. Upon (partial to full) surface crystallization of the F-free glass, the bioactivity (ability to form a reactive layer) was loss and the cytotoxicity again increased due to the rapid dissolution of one crystal phase and of the remaining amorphous phase. On another hand, the controlled bulk precipitation of CaF2 crystals, in the F-containing glass, was associated with a reduced cytotoxicity. The new oxyfluorophosphate glass-ceramic developed is promising for application in the biomedical field.

Characterization of the anisotropic deformation of the right ventricle during open heart surgery.

Digital Image Correlation (DIC) was used for studying the anisotropic behavior of the thin walled right ventricle of the human heart. Strains measured with Speckle Tracking Echocardiography (STE) were compared with the DIC data. Both DIC and STE were used to measure longitudinal strains of the right ventricle in the beginning of an open-heart surgery as well as after the cardiopulmonary bypass. Based on the results, the maximum end-systolic strains obtained with the DIC and STE change similarly during the surgery with less than 10% difference. The difference is largely due to the errors in matching the longitudinal direction in the two methods, sensitivity of the measurement to the positioning of the virtual extensometer of in both STE and DIC, and physiological difference of the measurements as the DIC measures the top surface of the heart whereas the STE obtains the data from below. The anisotropy of the RV was measured using full field principal strains acquired from the DIC displacement fields. The full field principal strains cover the entire region of interest instead of just two points as the virtual extensometer approach used by the STE. The principal strains are not direction dependent measures, and therefore are more independent of the anatomy of the patient and the exact positioning of the virtual strain gage or the STE probe. The results show that the longitudinal strains alone are not enough to fully characterize the behavior of the heart, as the deformation of the heart can be very anisotropic, and the anisotropy changes during the surgery, and from patient to patient.

An Optical Method for the In-Vivo Characterization of the Biomechanical Response of the Right Ventricle.

The intraoperative in-vivo mechanical function of the left ventricle has been studied thoroughly using echocardiography in the past. However, due to technical and anatomical issues, the ultrasound technology cannot easily be focused on the right side of the heart during open-heart surgery, and the function of the right ventricle during the intervention remains largely unexplored. We used optical imaging and digital image correlation for the characterization of the right ventricle motion and deformation during open-heart surgery. This work is a pilot study focusing on one patient only with the aim of establishing the framework for long term research. These experiments show that optical imaging and the analysis of the images can be used to obtain similar parameters, and partly at higher accuracy, for describing the mechanical functioning of the heart as the ultrasound technology. This work describes the optical imaging based method to characterize the mechanical response of the heart in-vivo, and offers new insight into the mechanical function of the right ventricle.

Crystallization and sintering of borosilicate bioactive glasses for application in tissue engineering.

Typical silicate bioactive glasses are known to crystallize readily during the processing of porous scaffolds. While such crystallization does not fully suppress the bioactivity, the presence of significantly large amounts of crystals leads to a decrease in the rate of reaction of the glass and an uncontrolled release of ions. Furthermore, due to the non-congruent dissolution of silicate glasses, these materials have been shown to remain within the surgical site even 14 years post-operation. Therefore, bioactive materials that can dissolve more effectively and have higher conversion rates are required. Within this work, boron was introduced, in the FDA approved S53P4 glass, at the expense of SiO2. The crystallization and sintering-ability of the newly developed glasses were investigated by differential thermal analysis. All the glasses were found to crystallize primarily from the surface, and the crystal phase precipitation was dependent on the quantity of B2O3 incorporated. The rate of crystallization was found to be lower for the glasses when 25, 50 and 75% of SiO2 was replaced with B2O3. These glasses were further sintered into porous scaffolds using simple heat sintering. The impact of glass particle size and heat treatment temperature on the scaffold porosity and average pore size was investigated. Scaffolds with porosity ranging from 10 to 60% and compressive strength ranging from 1 to 35 MPa were produced. The scaffolds remained amorphous during processing and their ability to rapidly precipitate hydroxycarbonate apatite was maintained. This is of particular interest in the field of tissue engineering as scaffold degradation and reaction is generally faster and offers higher controllability as opposed to the current partially/fully crystallized scaffolds obtained from the FDA approved bioactive glasses.