BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis.

Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass ( P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization. We also showed a marked increase in the expression of matrix metallopeptidase 13 (MMP13) and tartrate-resistant acid phosphatase (TRAP), leading to an acceleration in periodontal breakdown. Finally, we demonstrated that systemic application of antibiotics significantly improved the alveolar bone and PDL damage of the knockdown phenotype, which are thus shown to be partially secondary to pathogen-induced inflammation. Together, identification of the novel roles of BMP1 and TLL1 in maintaining homeostasis of periodontal formation, partly via biosynthetic processing of procollagen I and DMP1, provides novel insights into key contributions of the extracellular matrix environment to periodontal homeostasis and contributes toward understanding of the pathology of periodontitis.

Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life.

T helper 17 (Th17)-dependent autoimmune responses can develop after heart or lung transplantation and are associated with fibro-obliterative forms of chronic rejection; however, the specific self-antigens involved are typically different from those associated with autoimmune disease. To investigate the basis of these responses, we investigated whether removal of regulatory T cells or blockade of function reveals a similar autoantigen bias. We found that Th17 cells specific for collagen type V (Col V), kα1-tubulin, and vimentin were present in healthy adult peripheral blood mononuclear cells, cord blood, and fetal thymus. Using synthetic peptides and recombinant fragments of the Col V triple helical region (α1[V]), we compared Th17 cells from healthy donors with Th17 cells from Col V-reactive heart and lung patients. Although the latter responded well to α1(V) fragments and peptides in an HLA-DR-restricted fashion, Th17 cells from healthy persons responded in an HLA-DR-restricted fashion to fragments but not to peptides. Col V, kα1-tubulin, and vimentin are preferred targets of a highly conserved, hitherto unknown, preexisting Th17 response that is MHC class II restricted. These data suggest that autoimmunity after heart and lung transplantation may result from dysregulation of an intrinsic mechanism controlling airway and vascular homeostasis.

Hairy leukoplakia; lessons learned: 30-plus years.

Well into the fourth decade of the HIV/AIDS pandemic, we can look back on the early years, the initial discoveries, and the broad sweep of the progress of our understanding of the nature, causes, and significance of the oral lesions seen in those infected with the virus. Prominent among these is oral hairy leukoplakia (HL), a previously unknown lesion of the mouth associated with Epstein-Barr virus (EBV) and initially seen only in people with AIDS, in the then-recognized risk groups, or those shown to be HIV positive. Subsequently, it became clear that the distribution of HL extends well beyond the HIV spectrum. In this brief review, we consider the clinical and histological features of HL, discuss how it was discovered, explore its cause, diagnosis, relationship with AIDS, pathogenesis, significance in EBV biology, options for management, and how it changes with HIV/AIDS therapy.

Differential requirement for P2X7R function in IL-17 dependent vs. IL-17 independent cellular immune responses.

IL17-dependent autoimmunity to collagen type V (Col V) has been associated with lung transplant obliterative bronchiolitis. Unlike the T helper 1 (Th1)-dependent immune responses to Tetanus Toxoid (TT), the Th17 response to Col V in lung transplant patients and its Th1/17 variant observed in coronary artery disease patients requires IL-1ß, tumor necrosis factor α and CD14(+) cells. Given the involvement of the P2X7 receptor (P2X7R) in monocyte IL-1ß responses, we investigated its role in Th17-, Th1/17- and Th1-mediated proinflammatory responses. Transfer of antigen-pulsed peripheral blood mononucleated cells (PBMCs) from Col V-reactive patients into SCID mouse footpads along with P2X7R antagonists revealed a selective inhibition of Col V-, but not TT-specific swelling responses. P2X7R inhibitors blocked IL-1ß induction from monocytes, including both Col V-α1 peptide-induced (T-dependent), as well as native Col V-induced (T-independent) responses. Significantly higher P2X7R expression was found on CXCR3(neg) CCR4(+)/6(+) CD4(+) [Th17] versus CXCR3(+)CCR4/6(neg) CD4(+) [Th1] subsets in PBMCs, suggesting that the paradigm of selective dependence on P2X7R might extend beyond Col V autoimmunity. Indeed, P2X7R inhibitors suppressed not only anti-Col V, but also Th1/17-mediated alloimmunity, in a heart transplant patient without affecting anti-viral Epstein-Barr virus responses. These results suggest that agents targeting the P2X7R might effectively treat Th17-related transplant pathologies, while maintaining Th1-immunity to infection.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Physical and chemical characterization of dentin surface following treatment with NovaMin technology.

OBJECTIVE: The aim of this study was to characterize, in vitro, the mode of action of calcium sodium phosphosilicate (NovaMin) in occluding dentin tubules for the purpose of treating dentin hypersensitivity. METHODS: Calcium sodium phosphosilicate (CSPS) was combined with artificial saliva on surfaces of prepared dentin discs. The layer formed was initially examined by a scanning electron microscope (SEM). Focused ion beam (FIB) milling was used to make bulk cross-sections and thin film lamellae. Low kV scanning transmission electron microscopy (STEM), energy dispersive x-ray spectroscopy (EDS), and selected area electron diffraction were then used to characterize, chemically and structurally, the layer formed and the material occluding the tubules. Experiments were also performed to assess the suitability of using an environmental scanning electron microscope (ESEM) in wet mode to follow the transition from CSPS to hydroxyapatite. RESULTS: SEM imaging showed that a layer was formed on the treated dentin samples, and that this layer occluded tubules. Chemical and structural analysis of this material showed that it was hydroxyapatite-like. The wet mode ESEM experiments demonstrated that this technique has the potential to follow the transition from CSPS to the crystalline hydroxyapatite material. CONCLUSION: The use of modern imaging and analysis techniques has demonstrated, in vitro, the reaction of CSPS from an amorphous material to a crystalline hydroxyapatite-like material. These experiments confirmed an occlusion mode of action for CSPS for the treatment of dentin hypersensitivity.

Physical and chemical characterization of the surface layers formed on dentin following treatment with a fluoridated toothpaste containing NovaMin.

OBJECTIVE: To characterize in vitro the formation and robustness of a layer formed on dentin following treatment with a fluoridated toothpaste containing calcium sodium phosphosilicate (NovaMin) using modem imaging and analysis techniques. METHODS: Calcium sodium phosphosilicate (CSPS)-containing toothpaste was brushed on to etched dentin specimens twice daily for up to five days. In between applications the samples were stored in artificial saliva. Additionally, certain samples underwent a chemical challenge in the form of a dietary acid, whereby samples were exposed to a cola or grapefruit juice beverage for five minutes on day 4 of the five-day study. The ability of the CSPS-containing formulation to occlude tubules was assessed visually by scanning electron microscope (SEM) imaging and compared to a water control. In a second experiment, the mechanical resistance of the layer was assessed using profilometry after controlled brushing for 200 brush strokes with a wet medium-bristled toothbrush. To visualize the layer and characterize the tubule occlusion, longitudinal cross-sections were prepared using a focused ion beam scanning electron microscope (FIB SEM), and analysis performed by energy dispersive x-ray spectroscopy (EDS) and electron diffraction. Owing to the complexity of the mixed material deposited after application of the toothpaste, material from inside a dentin tubule was selectively removed after five days of treatment, and the morphologically different materials imaged and analyzed by electron diffraction in the transmission electron microscope (TEM). RESULTS: SEM inspection showed significant coverage of the dentin samples after application of CSPS toothpaste for all five days, in contrast to the water control where the majority of tubules remained open after all five days. Exposure of the NovaMin-treated samples to common dietary acids did not lead to re-exposure of the tubules. Profilometry measurements demonstrated an intact layer covering the dentin surface after one and five days. EDS analysis and electron diffraction indicated the layer and the material plugging the tubule to be a calcium phosphate material with a crystallographic structure similar to hydroxyapatite. CONCLUSION: CSPS contained in toothpaste formulations adhered to exposed dentin surfaces. The layer formed was resistant to acid and mechanical challenges. Characterization of this layer indicated it was hydroxyapatite-like in nature.

In-vivo and in-vitro histological evaluation of two commercially available acellular dermal matrices.

PURPOSE: Post-herniation abdominal wall repair can be performed with synthetic or biologic meshes. Synthetics have been associated with complications, so biologics are promising alternatives. The methods used to decellularize biological matrices may affect the extracellular components. This study evaluated the post-implantation biological response of two allogenic acellular dermal matrices (ADMs) in a hernia model. METHODS: Testing was conducted with two ADMs from different manufacturers: RTI Biologics (ADM-R) and LifeCell (ADM-L). Samples were evaluated for collagen IV, glycosaminoglycans (GAGs), and elastin before implantation. Samples were also used to repair bilateral full-thickness defects in rat abdominal walls. Pathologist evaluations included explant dimensions, inflammation, neovascularization, mature implant tissue, fibrosis, encapsulation, necrosis, mineralization, adhesions, granulomas, and hemorrhages at four and eight weeks post-implantation. RESULTS: GAG distribution in ADM-R samples was more consistent with native dermis than that in ADM-L samples. Collagen IV was visible in ADM-R, but not in ADM-L. The four-week ADM-R explants showed primarily lymphocytic infiltrates, and less inflammation at eight weeks. The four-week ADM-L explants showed primarily lymphocytic infiltrates, and sustained inflammation at eight weeks. Fibroplasia at four and eight weeks was higher in ADM-L than in ADM-R. Encapsulation, mature connective tissue, and vascular profile scores were comparable between groups. Picrosirius red image analysis showed no significant differences between groups. CONCLUSIONS: The post-processing matrix characterization and in-vivo response showed notable differences in these ADMs, despite similar allogenic origin. Future investigations into the different matrix composition with regard to fibrosis and inflammation are warranted.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS). DESIGN: Longitudinal cohort study. SUBJECTS AND METHODS: A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands. MAIN OUTCOME MEASURES: Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no). RESULTS: Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non-PI based HAART. CONCLUSIONS: PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.

Differential effects of bone graft substitutes on regeneration of bone marrow.

BACKGROUND: This study used a rat tibial marrow ablation model to test the hypothesis that bone remodeling within the medullary canal varies with bone graft materials of different chemical compositions and structural properties, impacting marrow cavity restoration. Bone graft materials were selected based on their relative resorption or degradation in vivo and their osteogenic properties. METHODS: Following ablation of the right tibial marrow in male Sabra-strain rats, materials were implanted in the proximal marrow cavity: poly-D,L-lactide-co-glycolide 75 : 25 (PLGA); coralline-hydroxyapatite (HA), calcium-sulfate (CaSO4), collagen-HA-tricalcium phosphate granules, anorganic bovine bone mineral, demineralized bone matrix (DBM), 45S5 Bioglass (BG), PLGA with BG 50 : 50, PLGA : BG 80 : 20, and PLGA and PLGA:BG 50 : 50 plus bone marrow (BM). Control tibias were ablated but received no implants. At 2 (endosteal bone healing), 4 (marrow cavity remodeling) and 8 weeks (marrow restoration), six to eight animals per group were euthanized and tibias processed for histomorphometry of proximal and distal medullary canals. RESULTS: Control tibias showed primary bone in proximal and distal medullary canals at 2 weeks, with trabeculae surrounded by cellular marrow. At 4 and 8 weeks, control trabeculae were thinned and marrow had more fat cells. In the treated tibias, trabecular bone volume (TBV) varied with time and was material specific. Most implants supported comparable TBV at 2 weeks. Sites with CaSO4 or DBM exhibited decreased TBV with time whereas trabecular bone was retained in proximal tibias containing other materials, closely juxtaposed to the implants. TBV did not always correlate directly with implant volume, but changes in BM volume were correlated inversely with TBV. Addition of BM increased marrow restoration in sites containing PLGA; however, BM reduced restoration of marrow when added to PLGA : BG. Although the presence of implants in the proximal tibia resulted in retention of trabecular bone, there was a time-dependent reduction in TBV in distal canals; the rate and extent of the distal TBV reduction were implant dependent. CONCLUSIONS: Thus, although many materials can support bone formation in the marrow cavity, bone quality, quantity, and physical relationship to the implant, and its rate of resorption differ in a material-dependent manner, resulting in differences in the restoration of marrow. CLINICAL RELEVANCE: Bone graft materials should be selected not only for their ability to support new bone formation but also for their impact on the remodeling phase of bone healing.

Oral health-related quality of life among HIV-infected and at-risk women.

OBJECTIVES: Objective measures of dental diseases reflect only their clinical end-point. There is a need to use multidimensional measures of diseases that consider their psychosocial aspects and functional impact. The aim of this study is to compare the oral health-related quality of life (OHRQOL) between a group of HIV-infected women and a similar group of at-risk HIV-uninfected women, and to investigate the role of potential confounding clinical oral health and behavioral factors. METHODS: Our sample included HIV-infected women (87%) and women at risk for HIV infection (13%) followed up for 5.5 years. OHRQOL was measured using the short version of the Oral Health Impact Profile (OHIP-14), which is a validated and reliable instrument. RESULTS: HIV-infected women averaged 10% poorer OHRQOL than HIV-uninfected women; this difference was not apparent after adjusting for the number of study visits attended and significant behavioral and clinical oral health factors. The OHRQOL was inversely related to dental and periodontal diseases and to smoking and freebase cocaine use; these relationships were not confounded by HIV status. CONCLUSIONS: The study identified specific clinical and behavioral factors where dental professionals can intervene to possibly improve the OHRQOL of HIV-infected or at-risk HIV-uninfected women.

Oral lesions of HIV disease and HAART in industrialized countries.

The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10-50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.

Potential of biomimetic surfaces to promote in vitro osteoblast-like cell differentiation.

Bioactive glasses, osteoproductive materials, have received considerable attention as bone graft substitutes in the treatment of bony defects. More recent strategies for achieving a predictable periodontal regeneration include the use of enamel matrix proteins, due to their role in the formation of bone tissue. The aim of our study is to examine the effects of these materials on the proliferation and differentiation of the mouse preosteoblastic cell line MC3T3-E1. Cells were cultured up to 28 days in contact with three types of granules: Bioglass 45S5 granules (BG), 45S5 granules coated with enamel matrix proteins (Emdogain) (BG/EMD), and a less reactive glass used as a control (60S). Phase contrast microscopic observations have shown that all substrates supported the growth of osteoblastic cells. Zones of differentiation were observed at an earlier stage in cultures of BG and BG/EMD. TEM observations revealed ultrastructural features very close to what is observed in vivo during intramembranous ossification with a direct bone apposition on the bioactive glasses. Total protein production was higher in the cultures with BG and BG/EMD. Northern Blot analysis revealed a stimulation of the transcription factor Cbfa1/Runx2 at day 13 in cultures of BG when compared to the two other cultures. Bone sialoprotein (early marker of differentiation) and osteocalcin (marker of late-stage differentiation) expression was increased in cultures with BG and BG/EMD when compared to 60S. Taken together, our findings indicate that Bioglass alone or combined with Emdogain, have the ability to support the growth of osteoblast-like cells in vitro and to promote osteoblast differentiation by stimulating the expression of major phenotypic markers. In addition, we noticed that the bioactive granules coated with Emdogain revealed significantly higher protein production than the bioactive granules alone at day 20.

Dental caries in HIV-seropositive women.

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals.

The disinhibition hypothesis of post-stroke central pain (CPSP) suggests that 'the excessive response (dysesthesia/hyperalgesia/allodynia) is accompanied by a em leader loss of sensation' resulting from a lesion of a 'lateral nucleus' of thalamus or of 'cortico-thalamic paths' [Brain 34 (1911) 102]. One recent elaboration of this hypothesis proposes a submodality specific relationship, such that injury to a cool-signaling lateral thalamic pathway disinhibits a nociceptive medial thalamic pathway, thereby producing both burning, cold, ongoing pain and cold allodynia. The current study quantitatively evaluated the sensory loss and sensory abnormalities to discern submodality relationships between these sensory features of CPSP. The present results were statistically tested within individuals so that sensory loss and sensory abnormality are directly related by occurrence in the same individual. The results demonstrate that individuals with CPSP and normal tactile detection thresholds experience tactile allodynia significantly more often than those with tactile hypoesthesia. Most patients (11/13) exhibited hypoesthesia for the perception of cool stimuli, but few of these (2/11) showed cold allodynia. The most dramatic case of cold allodynia occurred in a patient who had a normal detection threshold for cold. Individuals with cold hypoesthesia, strictly contralateral to the cerebro-vascular accident (CVA or stroke), were often characterized by the presence of burning, cold, ongoing pain, and by the absence, not the presence, of cold allodynia. Overall, these results in CPSP suggest that tactile allodynia occurs in disturbances of thermal/pain pathways that spare the tactile-signaling pathways, and that cold hypoesthesia is neither necessary nor sufficient for cold allodynia.

Incidence of oral lesions in HIV-1-infected women: reduction with HAART.

Few studies assess the effectiveness of HAART on reducing the incidence and recurrence of oral lesions. We investigated such changes among 503 HIV+ women over six years in the Women's Interagency HIV Study. The incidence of erythematous candidiasis (EC), pseudomembranous candidiasis (PC), hairy leukoplakia (HL), and warts was computed over follow-up visits after HAART initiation compared with before HAART initiation. Analysis of our data demonstrates a strong decrease in candidiasis after HAART initiation. The incidence of EC fell to 2.99% from 5.48% (RR 0.545); PC fell to 2.85% from 6.70% (RR 0.425); and EC or PC fell to 3.43% from 7.35% (RR 0.466). No changes were seen in HL or warts. Higher HIV-RNA was associated with greater incidence of candidiasis and HL, but not warts. Analysis of these data indicates that recurrence and incidence of candidiasis are reduced by HAART, and that recurrence is reduced independently of CD4 and HIV-RNA.

Osteoblast response to bioactive glasses in vitro correlates with inorganic phosphate content.

Inorganic phosphate (Pi) is a physiological regulator of osteoblasts and chondrocytes, suggesting that phosphate may contribute to the biological response of these cells to bioactive glasses like Bioglass 45S5, which is composed of 45% SiO2, 24.5% CaO, 24.5% Na2O, and 6% P2O5. We investigated the effect of varying the Pi content of bioactive glass disks (0%, 3%, 6% and 12% P2O5) using human osteoblast-like MG63 cells as the model. Cell number on 6% Pi disks was comparable to cultures on tissue culture plastic, but was reduced at higher and lower Pi concentrations. Alkaline phosphatase specific activity of isolated cells and cell layer lysates, as well as PGE2, TGF-beta1 and NO levels in conditioned media, were elevated in cultures grown on bioactive glass and varied with the Pi content. The greatest effects were observed in cultures grown on disks with the lowest Pi concentrations. Thus, growth on the bioactive glasses enhances cell function in comparison with tissue culture plastic and lower Pi content favors osteoblast differentiation.

A new quantitative method to evaluate the in vitro bioactivity of melt and sol-gel-derived silicate glasses.

Two melt-derived glasses (45S5 and 60S) and four sol-gel glasses (58S, 68S, 77S, and 91S) have been synthesized. The activation energy for the silicon release was determined, and a very close correlation was observed between this value and published results of the bioactive behavior of the glasses. This relationship can be explained in terms of the influence of chemical composition, textural properties, and structural density on the silanol group formation and silicon dissolution. These measurements provide a quantitative method to evaluate the in vitro bioactivity of SiO(2)-based glasses. Preliminary studies suggest an activation energy gap (Ea) of 0.35-0.5 eV as a boundary between bioactive and nonbioactive glasses.