Bioactive Glasses: Frontiers and Challenges.

Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong, and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics.

The future of bioactive ceramics.

Two important worldwide needs must be satisfied in the future; (1) treatment of the deteriorating health of an aging population and, (2) decreasing healthcare costs to meet the needs of an increased population. The ethical and economic dilemma is how to achieve equality in quality of care while at the same time decreasing cost of care for an ever-expanding number of people. The limited lifetime of prosthetic devices made from first-generation nearly inert biomaterials requires new approaches to meet these two large needs.

Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues.

The applications of bioactive glasses (BGs) have to a great extent been related to the replacement, regeneration and repair of hard tissues, such as bone and teeth, and there is an extensive bibliography documenting the role of BGs as bone replacement materials and in bone tissue engineering applications. Interestingly, many of the biochemical reactions arising from the contact of BGs with bodily fluids, in particular the local increase in concentration of various ions at the glass-tissue interface, are also relevant to mechanisms involved in soft tissue regeneration. An increasing number of studies report on the application of BGs in contact with soft tissues, aiming at exploiting the well-known bioactive properties of BGs in soft tissue regeneration and wound healing.

Compositional and microstructural design of highly bioactive P2O5-Na2O-CaO-SiO2 glass-ceramics.

Bioactive glasses having chemical compositions between 1Na(2)O-2CaO-3SiO(2) (1N2C3S) and 1.5Na(2)O-1.5CaO-3SiO(2) (1N1C2S) containing 0, 4 and 6 wt.

Twenty-first century challenges for biomaterials.

During the 1960s and 1970s, a first generation of materials was specially developed for use inside the human body. These developments became the basis for the field of biomaterials. The devices made from biomaterials are called prostheses.

Fabricating sol-gel glass monoliths with controlled nanoporosity.

Nanotopography is known to affect cell response, but the mechanisms are unknown. It is therefore important to be able to produce biomaterial surfaces with controllable nanopore sizes and morphologies from materials that can be used to make templates (scaffolds) for tissue regeneration. A rapid method of fabrication of sol-gel monoliths with controlled nanopore size is described in this paper.

Hierarchical porous materials for tissue engineering.

Biological organisms have evolved to produce hierarchical three-dimensional structures with dimensions ranging from nanometres to metres. Replicating these complex living hierarchical structures for the purpose of repair or replacement of degenerating tissues is one of the great challenges of chemistry, physics, biology and materials science. This paper describes how the use of hierarchical porous materials in tissue engineering applications has the potential to shift treatments from tissue replacement to tissue regeneration.

Extracellular matrix formation and mineralization on a phosphate-free porous bioactive glass scaffold using primary human osteoblast (HOB) cells.

Sol-gel derived bioactive glasses of the 70S30C (70mol% SiO2, 30mol% CaO) composition have been foamed to produce 3D bioactive scaffolds with hierarchical interconnected pore morphologies similar to trabecular bone. The aim of this study was to investigate primary human osteoblast response to porous bioactive glass scaffolds. The scaffolds supported osteoblast growth and induced differentiation, within the 3-week culture period, as depicted by enhanced ALPase enzymatic activity, without the addition of supplementary factors such as ascorbic acid, beta-glycerophosphate and dexamethasone.

Progress in Raman spectroscopy in the fields of tissue engineering, diagnostics and toxicological testing.

This review summarises progress in Raman spectroscopy and its application in diagnostics, toxicological testing and tissue engineering. Applications of Raman spectroscopy in cell biology are in the early stages of development, however, recent publications have demonstrated its utilisation as a diagnostic and development tool with the key advantage that investigations of living cells can be performed non-invasively.Some of the research highlighted here demonstrates the ability of Raman spectroscopy to accurately characterise cancer cells and distinguish between similar cell types.

The use of advanced diffraction methods in the study of the structure of a bioactive calcia: silica sol-gel glass.

Sol-gel derived calcium silicate glasses may be useful for the regeneration of damaged bone. The mechanism of bioactivity is as yet only partially understood but has been strongly linked to calcium dissolution from the glass matrix. In addition to the usual laboratory-based characterisation methods, we have used neutron diffraction with isotopic substitution to gain new insights into the nature of the atomic-scale calcium environment in bioactive sol-gel glasses, and have also used high energy X-ray total diffraction to probe the nature of the processes initiated when bioactive glass is immersed in vitro in simulated body fluid.

Controlling ion release from bioactive glass foam scaffolds with antibacterial properties.

Bioactive glass scaffolds have been produced, which meet many of the criteria for an ideal scaffold for bone tissue engineering applications, by foaming sol-gel derived bioactive glasses. The scaffolds have a hierarchical pore structure that is very similar to that of cancellous bone. The degradation products of bioactive glasses have been found to stimulate the genes in osteoblasts.

The story of Bioglass.

Historically the function of biomaterials has been to replace diseased or damaged tissues. First generation biomaterials were selected to be as bio-inert as possible and thereby minimize formation of scar tissue at the interface with host tissues. Bioactive glasses were discovered in 1969 and provided for the first time an alternative; second generation, interfacial bonding of an implant with host tissues.

In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy.

Raman micro-spectroscopy combined with multivariate analysis was employed to monitor real-time biochemical changes induced in living cells in vitro following exposure to a pharmaceutical. The cancer drug etoposide (topoisomerase II inhibitor) was used to induce double-strand DNA breaks in human type II pneumocyte-like cells (A549 cell-line). Raman spectra of A549 cells exposed to 100 microM etoposide were collected and classical least squares (CLS) analysis used to determine the relative concentrations of the main cellular components.

Raman microspectroscopy: a noninvasive tool for studies of individual living cells in vitro.

There is an increasing need for noninvasive methods that are able to monitor individual live cells in vitro, including in vitro testing of chemicals and pharmaceuticals, monitoring the growth of engineered tissues and the development of cell-based biosensors. Raman spectroscopy is a pure optical technique based on inelastic scattering of laser photons by molecular vibrations of biopolymers, which provide a chemical fingerprint of cells or organelles without fixation, lysis or the use of labels and other contrast-enhancing chemicals. Changes in cells during the cell cycle, cell death, differentiation or during the interaction with various chemicals or materials involve biochemical changes that can be measured with high spatial ( approximately 300 nm) and temporal (seconds to minutes) resolution.

Characterization of human fetal osteoblasts by microarray analysis following stimulation with 58S bioactive gel-glass ionic dissolution products.

Bioactive glasses dissolve upon immersion in culture medium, releasing their constitutive ions in solution. There is evidence suggesting that these ionic dissolution products influence osteoblast-specific processes. Here, we investigated the effect of 58S sol-gel-derived bioactive glass (60 mol % SiO2, 36 mol % CaO, 4 mol % P2O5) dissolution products on primary osteoblasts derived from human fetal long bone explant cultures (hFOBs).

Preparation of poly(L-lactic acid)-polysiloxane-calcium carbonate hybrid membranes for guided bone regeneration.

A novel poly(L-lactic acid) (PLLA)/calcium carbonates hybrid membrane containing polysiloxane was prepared using aminopropyltriethoxysilane (APTES) for biodegradable bone-guided regeneration. Carboxy groups in the PLLA made a chemical bond with amino groups in APTES, resulting in the formation of the hybrid membrane. The polysiloxane-hybridized PLLA was an amorphous phase.

Optimising bioactive glass scaffolds for bone tissue engineering.

A 3D scaffold has been developed that has the potential to fulfil the criteria for an ideal scaffold for bone tissue engineering. Sol-gel derived bioactive glasses of the 70S30C (70 mol% SiO2, 30 mol% CaO) composition have been foamed to produce 3D bioactive scaffolds with hierarchical interconnected pore morphologies similar to trabecular bone. The scaffolds consist of a hierarchical pore network with macropores in excess of 500 microm connected by pore windows with diameters in excess of 100 microm, which is thought to be the minimum pore diameter required for tissue ingrowth and vasularisation in the human body.

Dose- and time-dependent effect of bioactive gel-glass ionic-dissolution products on human fetal osteoblast-specific gene expression.

Bioactive glasses dissolve upon immersion in culture medium, and release their constitutive ions into solution. There has been some evidence suggesting that these ionic-dissolution products influence osteoblast-specific processes. Here, the effect of 58S sol-gel-derived bioactive glass (60% SiO(2), 36% CaO, 4% P(2)O(5), in molar percentage) on primary osteoblasts derived from human fetal long bone explant cultures is investigated, and it is hypothesized that critical concentrations of sol-gel-dissolution products (consisting of a combination of simple inorganic ions) can enhance osteoblast phenotype in vitro by affecting the expression of a number of genes associated with the differentiation and extracellular matrix deposition processes.

Enhanced derivation of osteogenic cells from murine embryonic stem cells after treatment with ionic dissolution products of 58S bioactive sol-gel glass.

Embryonic stem (ES) cells represent a potentially useful cell source for tissue regeneration. Previously, using factors known to enhance differentiation and mineralization of primary osteoblasts, we were able to generate cell populations enriched with osteoblasts from a murine ES cell source. Dexamethasone was a potent inducer of osteoblast differentiation and the timing of stimulation markedly increased the proportion of osteoblast lineage cells.

Effect of taper geometries and launch angle on evanescent wave penetration depth in optical fibers.

A large penetration depth of an evanescent wave is the key to success for developing an ultra high-resolution fiber-based evanescent wave biosensor. Tapering the fiber and launching light at an angle has the potential of increasing the penetration depth of evanescent wave manifolds. The effects of tapering, launch angle and taper length of the fiber have been explored in detail using a ray-tracing model to calculate the highest possible penetration depth of the evanescent field.

New detection system for toxic agents based on continuous spectroscopic monitoring of living cells.

In this study, we show the feasibility of a new type of cell based biosensor which uses spectroscopic in situ real time detection of biochemical changes in living cells exposed to toxic chemical agents. We used a high power 785 nm laser to measure the time dependent changes in the Raman spectrum of individual living human lung cells (A549 cell line) treated with a toxic agent (Triton X-100, 250 microM solution). Individual cells were monitored by Raman spectroscopy over a total time span of 420 min, with 30 min sampling intervals.

Binary CaO-SiO(2) gel-glasses for biomedical applications.

Bioactive materials are routinely used in dental and orthopaedic applications. The concept was first introduced in 1971, with the discovery of 45S5 Bioglass, which is known to develop an interfacial bond between the implant and the host tissue. This glass is composed of SiO(2), CaO, P(2)O(5) and Na(2)O.

Bioactive evaluation of 45S5 bioactive glass fibres and preliminary study of human osteoblast attachment.

Bioactive glass fibres can be used as tissue engineering scaffolds. In this investigation, the bioactive response of 45S5 glass fibres was assessed in simulated body fluid (SBF). Preliminary attachment of osteoblasts to the fibre surface was assessed, as were the fibre tensile strength and fracture toughness.

Time- and concentration-dependent effects of dissolution products of 58S sol-gel bioactive glass on proliferation and differentiation of murine and human osteoblasts.

Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold.

In situ non-invasive spectral discrimination between bone cell phenotypes used in tissue engineering.

Raman micro-spectroscopy was used to discriminate between different types of bone cells commonly used in tissue engineering of bone, with the aim of developing a method of phenotypic identification and classification. Three types of bone cells were analysed: human primary osteoblasts (HOB), retroviral transfected human alveolar bone cells with SV40 large T antigen (SV40 AB), and osteoblast-like human osteosarcoma derived MG63 cell line. Unsupervised principal component analysis (PCA) and linear discriminant analysis (LDA) of the Raman spectra succeeded in discriminating the osteosarcoma derived MG63 cells from the non-tumour cells (HOB and SV40 AB).