Three glasses were designed for this study, where the bioactive glass SiO2-CaO-Na2O-P2O5 labeled BG, 9 wt. % substitution of TiO2 for CaO and Na2O was marked with SC-1 and SC-2, respectively. Although the hardness of SC-1 and SC-2 was found to decrease significantly after each incubation period, when incubated for 1000 h, SC-1 and SC-2 showed higher mechanical durability than BG.
Glass
Network Structure
Zachariasen stated four rules for the formation of glass in oxides where: first, one oxygen atom is connected to no more than two atoms of the network formers, the second is the coordination number of the network formers with oxygen either 3 or 4, the third is the shared corners of the polyhedron, and the last is that at least three corners of the polyhedron must be shared 1. One of the biggest disadvantages of some glass as a material is its vulnerability to chemical attack in fluid media 5-9.
Glass Composition
One of the many problems associated with regular bioactive glass is its mechanical strength when manufactured in scaffolds. Thus, the following glass system of 30SiO2-28Na2O-27CaO-15P2O5 in wt% was produced as a bioactive control glass (BG) in this study, and resulted in a substitution of 9% TiO2 with Na2O (denoted as SC-1).
Titanium Inclusion
Also, attempts to increase bioactivity and cell adhesion to bioactive glass, as well as bioactive glass-derived scaffolds, have been extensively investigated, which will be addressed in the literature review. Three samples were prepared to investigate how effective TiO2 can be in offsetting the drawbacks of mainstream bioactive glass currently in use, and to determine which glass system can be appropriately fabricated into scaffolds for bone tissue engineering applications.
Modified Glass
Bioactivity Improvement
Amorphous vs. Crystalline
Mechanical Properties
Therefore, it is of great interest to modify the composition of bioactive glass to effectively induce bioactivity through its amorphous structure and exhibit high mechanical properties. This study aims to investigate the substitution of TiO2 for network modifiers in bioactive glass to determine its effect on the glass structure and bioactive properties when incubated in simulated body fluid (SBF).
Requirement of Medical Materials
Fracture Repair
- Inflammation
- Soft Callus
- Hard Callus
- Bone Remodeling
After the removal of degenerated cells, the formation of a bone callus is catalyzed by a cartilage template 37. After the formation of new bone with vascular integration, the final step of bone remodeling takes place.
Bone Disease
- Osteoporosis
- RicketsandOsteomalacia
- Paget’s Disease
The decrease in bone density due to osteoporosis makes the bone more vulnerable and at high risk of fracture. Paget's disease is a condition in the body where osteoclasts exhibit uncontrolled activity, leading to abnormal bone resorption.
Bone Void Filling
However, it is important to note that specific types of genetic mutations that support such statements have not yet been answered, as other studies have shown that measles viral infection can also be the cause of such a condition66. Such complications with the use of both autografts and allografts ultimately lead to the development of synthetic bone graft materials. Synthetic bone grafts have been shown to exhibit only two of the four characteristics that make an ideal material for filling bone voids, namely osteointegration and osteoconduction.
However, it has been reported that various types of synthetic materials have been used over many years in clinical use 73. Synthetic materials include alumina, calcium sulfate, beta-tricalcium phosphate, hydroxyapatite to mimic bone structure, and finally bioactive glass. To compensate for the other two properties that an ideal bone graft material would have, bioactive glass with components such as calcium and silicon has been widely studied.
Medical Glasses
Bioglass
Bioactive Response
- General Overview
- Simulated Body Fluid (SBF)
- Silanol Group Formation
- SiO 2 -Rich Surface Layer Formation
- Calcium & Phosphate Adsorption
- CaP Deposition Layer
- Hydroxyl-Carbonate Apatite (HCA) Crystallization
- Osteoblast Attachment
The modifying ions are exchanged with H3O+, leaving the OH- groups to form silanol groups on the glass surface. Such silanol groups are then distributed across the surface of the material, which marks the beginning of the bioactivity process. Then through the adsorption of calcium and phosphate ions on the surface, the SiO2-rich layer eventually becomes a crystalline HCA layer that covers the entire surface of the glass 82.
The surface layer of glass rich in SiO2, due to polycondensation of silanol groups, attracts positively charged ions such as calcium and phosphate from body fluids. As mentioned above, the absorption of calcium and phosphate leads to the deposition of the CaP layer on the glass surface over the SiO2-rich layer. Once an amorphous Ca/P layer on the implant surface exhibits a Ca/P ratio similar to that of bone, calcium and phosphate absorption is interrupted 89 .
Scaffolds
Bioglass Derived Scaffolds
It has been reported by several authors that bioactive glass as a base material fulfills the following three requirements: excellent bioactivity with osteoconductivity. When producing bioactive glass in scaffolds, the foam replication method is commonly used because the scaffolds produced by this method meet three other properties mentioned above: high porosity structure, flexibility in shape and commercialization potential. It is important to note that 45S5 Bioglass®-derived scaffolds do not meet the mechanical characteristic when fabricated by foaming the replication technique and thus modification of scaffolding has received attention among researchers.
At this point, the polymeric template is burned off and the result is fully sintered bioactive glass-ceramic-derived scaffold.
Current Drawbacks to Bioglass Scaffolds
Modification Methods
Clearly, several modifications have been explored to improve the currently known drawbacks of Bioglass-derived scaffolds. However, achieving mechanical stability with preserved amorphous structure of scaffolds exhibiting better cell attachment/viability than currently known scaffolds has not been introduced. This study will synthesize and characterize the glass composition modified to replace TiO2 with network modifiers such as Na2O and CaO in terms of glass structure, and measure the mechanical properties when immersed in simulated body fluid for a series of hours.
Then, the appropriate choice of glass composition after comparing properties will be incorporated into scaffolds via polymer foam replication, where structural characterization and visual analysis will be noted. With current knowledge of bioactive glass-derived scaffolds, it is hypothesized that replacement of TiO2 within the glass system will increase the network stability of the glass. In other words, the next generation of bioactive glass-derived scaffolds that maintain the amorphous structure with higher mechanical strength and better cell adhesion.
Glass Synthesis
Glass Production
Glass Powder Production
Material Characterization
- X-ray Diffraction (XRD)
- X-ray Photoelectron Spectroscopy (XPS)
- Particle Size Analysis (PSA)
- Scanning Electron Microscopy/Energy Dispersive Spectroscopy (SEM/EDS)
- Differential Thermal Analysis (DTA)
- Hot Stage Microscopy (HSM)
- Magic Angle Spinning Nuclear Magnetic Resonance (MAS-NMR)
The C 1s peak of random carbon at 284.8 eV was used as a charge reference to calibrate binding energies. Particle size analysis was performed using a Beckman Coulter Multisizer 4 particle size analyzer (Beckman Coulter, Fullerton, CA, USA). NaCl solution was used as the solvent and testing was carried out at the standard laboratory temperature range of 25 °C.
A MISURA side view hot stage microscope (HSM), Expert Systems, (Modena, Italy), with image analysis system and electric oven, with maximum temperature of 1600˚C and maximum speed of 80˚C/min. The recycle delays were chosen to be three times the spin lattice relaxation times, which were determined to be between 15s and 26s by inversion recovery sequences. The chemical shift scale was compared externally with kaolin as a secondary chemical shift standard at -91.34 ppm (midpoint between doublet).
Sample Preparation of Incubation Media
Sample Preparation
However, both SC-1 and SC-2 showed greater distribution of Q species where the majority of the glass showed presence of Q2 and Q3 (where Q3 was 48% and 60% respectively) as shown in Figure 26. At 1,000 hour, it is clearly visible that the calcium phosphate deposit has formed a layer on top of the surface as in Fig. Both glasses showed no visible indication of the deposit layer present on the surface.
SC-1 and SC-2 also showed similar trend where the hardness of the glasses has decreased during the incubation time. The small increase in the hardness strength of SC-1 after 10 hours can possibly be explained by the rapid formation of SiO2-rich layer on the glass surface. It has been found that the substitution of TiO2 in bioactive glass has increased the initial hardness strength of the glass drastically as expected.
Simulated Body Fluid (SBF) Preparation
Glass Solubility Analysis
Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES)
Mechanical Evaluation
Hardness Testing
Scaffold Synthesis
Synthesis Method
Scaffold Characterization
X-ray Diffraction (XRD)
Optical Stereomicroscopy
- X-ray Diffraction (XRD)
- X-ray Photoelectron Spectroscopy (XPS)
- Particle Size Analysis (PSA)
- Scanning Electron Microscopy/Energy Dispersive Spectroscopy (SEM/EDS)
- Differential Thermal Analysis (DTA)
- Hot Stage Microscopy (HSM)
- Magic Angle Spinning Nuclear Magnetic Resonance (MAS-NMR)
For example, the observation of the presence of Ti4+ can be made in SC-1 and SC-2, but not in BG, as shown in Figure 18. An additional observation can be made about the difference in Na+ intensity detected by XPS in SC-1 . Therefore, it is important to note that all three glasses produced in this study do not show significant differences in particle size distribution and it can be safely assumed that differences in mean particle sizes do not affect any significant change in the ion release profile.
The particle morphology was irregular in shape, but all three glasses showed a similar morphology where a range of particle sizes up to 300~400 can be seen. SC-2 can be observed with the highest Ts, Tf and Tm among the three glasses, while SC-1 shows the lowest Ts and Tm compared. It can be seen from Figure 26 that a reduction of the Q3 and Q4 species can be observed when Ti is introduced into the glass lattice.
Ti 4+ Effect on Glass Solubility & in vitro Bioactivity
- Scanning Electron Microscopy/Energy Dispersive Spectroscopy (SEM/EDS)
- Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES)
- pH Analysis
- Hardness
Cracks on the BG surface can also be attributed to dehydration during preparation for analysis. 28 and 29 several studies have reported that Ti-containing materials induce calcium phosphate deposition on the surface when incubated in SBF 33,147. Although the deposition of calcium phosphate on the surface of SC-1 was not clearly visible by SEM images, the ion release profile showed evidence of dissolution and general reduction of Ca and P, supporting very low amounts of calcium deposition on the surface layer of the glasses.
The initial release of Si4+ in the SBF can cause Si-OH group to form on the surface, which then attracts Ca and P to form an amorphous calcium phosphate deposition layer. Thus, due to increased bioactivity of SC-1 compared to SC-2, chemical modification on the surface may have caused a slight change in mechanical properties. Furthermore, it is reasonable to state no significant difference in hardness based on the amount of crystallinity present in the glass as similar mechanical characteristics can be observed for both SC-1 and SC-2.
Scaffold Synthesis & Characterization
X-ray Diffraction (XRD)
Optical Imaging
The main objective of this study was to fabricate bioactive glass-derived scaffolds with modified glass compositions in order to compensate for common drawbacks that are currently challenging to overcome. Yehia, "Effect of heat treatment on bioactive glass microstructure, corrosion behavior, Ζ potential and protein adsorption," J. Boccaccini, "Development and Characterization of Silver-Doped Glass-Coated Bioactive Sutures for Tissue and Wound Engineering Biological," .
Brown, “Preparation and in vitro Evaluation of Bioactive Glass (13–93) Scaffolds with Oriented Microstructures for Repair and Regeneration of Load-bearing Bones,” J. 34; Novel Biodegradable Chitosan-Gelatin/Nano-Bioactive Glass Ceramic Composite Scaffolds for Alveolar Bone Tissue Engineering", Chem. Greenspan, "Sintering Temperature Effects on the In Vitro Bioactive Response of Cast Tape and Sintered Bioactive Glass Ceramics in Tris Buffer", J.
