Mohamed N. Rahaman

Bioactive glass in tissue engineering

This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed.

Sintering of Ceramics

Sintering of Ceramics: Fundamentals The Sintering Process Driving Force for Sintering Defects in Crystalline Solids Diffusion in Crystalline Solids The Chemical Potential Diffusional Flux Equations Diffusion in Ionic Crystals: Ambipolar Diffusion Solid-State and Viscous Sintering Mechanisms of Sintering Effects of Grain Boundaries Theoretical Analysis of Sintering Herrings Scaling Law Analytical Models Numerical Simulation of Sintering Phenomenological Sintering Equations Sintering Diagrams Sintering with an Externally Applied Pressure Stress Intensification Factor and Sintering Stress Alternative Derivation of the Sintering Equations Grain Growth and Microstructure Control General Features of Grain Growth Ostwald Ripening Topological and Interfacial Tension Requirements Normal Grain Growth in Dense Solids Abnormal Grain Growth in Dense Solids Grain Growth in Thin Films Mechanisms Controlling the Boundary Mobility Grain Growth and Pore Evolution in Porous Solids Simultaneous Densification and Grain Growth Fabrication Principles for Ceramics with Controlled Microstructure Liquid-Phase Sintering Elementary Features of Liquid-Phase Sintering Stages of Liquid-Phase Sintering Grain Boundary Films The Basic Mechanisms of Liquid-Phase Sintering Numerical Modeling of Liquid-Phase Sintering Hot Pressing with a Liquid Phase Use of Phase Diagrams in Liquid-Phase Sintering Activated Sintering Vitrification Special Topics in Sintering Inhomogeneities and their Effects on Sintering Constrained Sintering I: Rigid Inclusions Constrained Sintering II: Adherent Thin Films Constrained Sintering III: Multilayers Constitutive Models for Porous Sintering Materials Morphological Stability of Continuous Phases Solid Solution Additives and the Sintering of Ceramics Sintering with Chemical Reaction: Reaction Sintering Viscous Sintering with Crystallization Sintering Process Variables and Sintering Practice Sintering Measurement Techniques Conventional Sintering Microwave Sintering Pressure-Assisted Sintering Appendix A Physical Constants Appendix B SI Units - Names and Symbols Appendix C Conversion of Units Appendix D Ionic Crystal Radii (in units of 10-10m) Appendix E Density and Melting Point of Some Elements and Ceramics

Mechanical and in vitro performance of 13–93 bioactive glass scaffolds prepared by a polymer foam replication technique

A polymer foam replication technique was used to prepare porous scaffolds of 13-93 bioactive glass with a microstructure similar to that of human trabecular bone. The scaffolds, with a porosity of 85+/-2% and pore size of 100-500 microm, had a compressive strength of 11+/-1 MPa, and an elastic modulus of 3.0+/-0.5 GPa, approximately equal to the highest values reported for human trabecular bone. The strength was also considerably higher than the values reported for polymeric, bioactive glass-ceramic and hydroxyapatite constructs prepared by the same technique and with the equivalent level of porosity. The in vitro bioactivity of the scaffolds was observed by the conversion of the glass surface to a nanostructured hydroxyapatite layer within 7 days in simulated body fluid at 37 degrees C. Protein and MTT assays of in vitro cell cultures showed an excellent ability of the scaffolds to support the proliferation of MC3T3-E1 preosteoblastic cells, both on the surface and in the interior of the porous constructs. Scanning electron microscopy showed cells with a closely adhering, well-spread morphology and a continuous increase in cell density on the scaffolds during 6 days of culture. The results indicate that the 13-93 bioactive glass scaffolds could be applied to bone repair and regeneration.

Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation

Bioactive glass scaffolds with a microstructure similar to that of dry human trabecular bone but with three different compositions were evaluated for potential applications in bone repair. The preparation of the scaffolds and the effect of the glass composition on the degradation and conversion of the scaffolds to a hydroxyapatite (HA)-type material in a simulated body fluid (SBF) are reported here (Part I). The in vitro response of osteogenic cells to the scaffolds and the in vivo evaluation of the scaffolds in a rat subcutaneous implantation model are described in Part II. Scaffolds (porosity = 78-82%; pore size = 100-500 microm) were prepared using a polymer foam replication technique. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13-93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. The conversion rate of the scaffolds to HA in the SBF increased markedly with the B2O3 content of the glass. Concurrently, the pH of the SBF also increased with the B2O3 content of the scaffolds. The compressive strengths of the as-prepared scaffolds (5-11 MPa) were in the upper range of values reported for trabecular bone, but they decreased markedly with immersion time in the SBF and with increasing B2O3 content of the glass. The results show that scaffolds with a wide range of bioactivity and degradation rate can be achieved by replacing varying amounts of SiO(2) in silicate bioactive glass with B2O3.

Hydrothermal synthesis and sintering of ultrafine CeO2 powders

Undoped CeO2 and Y2O3-doped CeO2 powders, with particle sizes of almost-equal-to 10-15 nm, were prepared under hydrothermal conditions of 10 MPa at 300-degrees-C for 4 h. The compacted powders were sintered freely in air or in O2 at constant heating rates of 1-10-degrees-C/min up to 1350-degrees-C. The undoped CeO2 started to sinter at almost-equal-to 800-900-degrees-C and reached a maximum density of 0.95 of the theoretical at 1200-degrees-C, after which the density decreased slightly. Isothermal sintering at 1150-degrees-C produced a sample with a relative density of almost-equal-to 0.98 and an average grain size of almost-equal-to 100 nm. The samples sintered above 1200-degrees-C exhibited microcracking. The decrease in density and the microcracking above 1200-degrees-C are attributed to a redox reaction leading to the formation of oxygen vacancies and the evolution Of O2 gas. Doping with Y2O3 produced an increase in the temperature at which measurable sintering commenced and an increase in the sintering rate, compared with the undoped CeO2. Sintered samples of the doped CeO2 showed no microcracks. The CeO2 doped with up to 3 mol % Y2O3 was sintered to almost full density and with a grain size of almost-equal-to 200 nm at 1400-degrees-C.

TRANSIENT STRESSES IN BIMODAL COMPACTS DURING SINTERING

Abstract A method is described and used to evaluate the transient stresses in a sintering compact of ZnO containing a hard, dense dispersion of SiC. A hard second phase can severely limit densification rates by generating a mean hydrostatic stress, σh, which opposes the compressive sintering stress of the matrix. σh rapidly increases with increasing volume fraction, ƒ, of the second phase. The interface stress, σi., at the ZnO SiC boundary increases with decreasing ƒ, σi can attain large values, especially in the intermediate stage of sintering. The effect of these stresses on microstructural development is considered.

Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro and in vivo biological evaluation

In Part I, the in vitro degradation of bioactivAR52115e glass scaffolds with a microstructure similar to that of human trabecular bone, but with three different compositions, was investigated as a function of immersion time in a simulated body fluid. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13-93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. This work is an extension of Part I, to investigate the effect of the glass composition on the in vitro response of osteogenic MLO-A5 cells to these scaffolds, and on the ability of the scaffolds to support tissue infiltration in a rat subcutaneous implantation model. The results of assays for cell viability and alkaline phosphatase activity showed that the slower degrading silicate 13-93 and borosilicate 13-93B1 scaffolds were far better than the borate 13-93B3 scaffolds in supporting cell proliferation and function. However, all three groups of scaffolds showed the ability to support tissue infiltration in vivo after implantation for 6 weeks. The results indicate that the required bioactivity and degradation rate may be achieved by substituting an appropriate amount of SiO2 in 13-93 glass with B2O3, and that these trabecular glass scaffolds could serve as substrates for the repair and regeneration of contained bone defects.

Mechanical properties of bioactive glass (13-93) scaffolds fabricated by robotic deposition for structural bone repair

There is a need to develop synthetic scaffolds to repair large defects in load-bearing bones. Bioactive glasses have attractive properties as a scaffold material for bone repair, but data on their mechanical properties are limited. The objective of the present study was to comprehensively evaluate the mechanical properties of strong porous scaffolds of silicate 13-93 bioactive glass fabricated by robocasting. As-fabricated scaffolds with a grid-like microstructure (porosity 47%, filament diameter 330μm, pore width 300μm) were tested in compressive and flexural loading to determine their strength, elastic modulus, Weibull modulus, fatigue resistance, and fracture toughness. Scaffolds were also tested in compression after they were immersed in simulated body fluid (SBF) in vitro or implanted in a rat subcutaneous model in vivo. As fabricated, the scaffolds had a strength of 86±9MPa, elastic modulus of 13±2GPa, and a Weibull modulus of 12 when tested in compression. In flexural loading the strength, elastic modulus, and Weibull modulus were 11±3MPa, 13±2GPa, and 6, respectively. In compression, the as-fabricated scaffolds had a mean fatigue life of ∼10(6) cycles when tested in air at room temperature or in phosphate-buffered saline at 37°C under cyclic stresses of 1-10 or 2-20MPa. The compressive strength of the scaffolds decreased markedly during the first 2weeks of immersion in SBF or implantation in vivo, but more slowly thereafter. The brittle mechanical response of the scaffolds in vitro changed to an elasto-plastic response after implantation for longer than 2-4weeks in vivo. In addition to providing critically needed data for designing bioactive glass scaffolds, the results are promising for the application of these strong porous scaffolds in loaded bone repair.

Effect of redox reaction on the sintering behavior of cerium oxide

Hydrothermally synthesized nano-size CeO2 powders, chemically precipitated CeO2 powders and commercial micron-size CeO2 powders were investigated by DTA/TGA and TEM. The sintering behavior of these powders was studied by continuous monitoring of the shrinkage kinetics. The microstructural features of the sintered specimens were observed by SEM. The sinterability of the CeO2 powder compact increased with decrease in particle size. During the high temperature sintering process a redox reaction occurred, i.e. CeO2 was reduced to Ce2O3, and oxygen gas was released. The redox reaction influenced the sintering behavior of CeO2, resulting in a decrease in density and microcracking for the hydrothermally synthesized nano-size CeO2 powder compacts, and sagged points in the sintering curves for the chemically precipitated and commercial micron-size CeO2 powder compacts. It was found that the redox reaction of ceria produced additional pores during the sintering process and thus a much higher temperature was needed to achieve a high density

Effect of borate glass composition on its conversion to hydroxyapatite and on the proliferation of MC3T3‐E1 cells

Glasses containing varying amounts of B(2)O(3) were prepared by partially or fully replacing the SiO(2) in silicate 45S5 bioactive glass with B(2)O(3). The effects of the B(2)O(3) content of the glass on its conversion to hydroxyapatite (HA) and on the proliferation of MC3T3-E1 cells were investigated in vitro. Conversion of the glasses to HA in dilute (20 mM) K(2)HPO(4) solution was monitored using weight loss and pH measurements. Proliferation of MC3T3-E1 cells was determined qualitatively by assay of cell density at the glass interface after incubation for 1 day and 3 days, and quantitatively by fluorescent measurements of total DNA in cultures incubated for 4 days. Higher B(2)O(3) content of the glass increased the conversion rate to HA, but also resulted in a greater inhibition of cell proliferation under static culture conditions. For a given mass of glass in the culture medium, the inhibition of cell proliferation was alleviated by using glasses with lower B(2)O(3) content, by incubating the cell cultures under dynamic rather than static conditions, or by partially converting the glass to HA prior to cell culture.