The Angiogenic Potential Of PH-neutral Borophosphate Bioactive Glasses

Borate bioactive glasses have gained attention in recent years due to their therapeutic and regenerative effects in vivo. However, borate bioactive glasses release alkaline ions, increasing the local pH and creating a toxic environment for cell culture studies. A partial compositional substitution of phosphate for borate can create a pH-neutral glass that does not significantly affect the local pH while still releasing therapeutic ions. In the present study, a series of Na-Ca-borophosphate bioactive glasses with different borate-to-phosphate ratios was evaluated in vitro and in vivo for cytotoxicity and angiogenic effects. Compared to more basic borate glasses, the pH-neutral glasses supported endothelial cell migration and stimulated greater blood vessel formation in a chick chorioallantoic membrane model. The results from this study indicate that these pH-neutral glasses are promising angiogenic biomaterials for use in tissue engineering and regenerative medicine

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Bioprinting with Human Stem Cell-Laden Alginate-Gelatin Bioink and Bioactive Glass for Tissue Engineering

Three-dimensional (3D) bioprinting technologies have shown great potential in the fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin (Alg-Gel) hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12 x 12 x 1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alg-Gel composite hydrogel is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate the feasibility of the solvent-based bioprinting process to fabricate 3D cellularized scaffolds with more than 80% viability on day 0. The decrease in viability after 7 days due to glass concentration and static culture conditions is discussed. The feasibility of modifying Alg-Gel with 13-93B3 glass for bioprinting is also investigated, and the results are discussed

Bioactive Borate Glass Triggers Phenotypic Changes in Adipose Stem Cells

A bioactive borate glass, 13-93B3 (B3), has been used successfully in the clinic to treat chronic, nonhealing wounds without scarring. However, the mechanism by which B3 stimulates wound healing is poorly understood. Because adipose stem cells (ASCs) have been shown to have multiple roles in wound repair, we hypothesized that B3 triggers ASCs. In this study, we evaluate the effects of B3 on ASC survival, migration, differentiation, and protein secretion in vitro. In concentrations ≤10 mg/ml, B3 did not affect ASC viability under static conditions. B3 promoted the migration of ASCs but did not increase differentiation into bone or fat. B3 also decreased ASCs secretion of collagen I, PAI-1, MCP-1, DR6, DKK-1, angiogenin, IL-1, IGFBP-6, VEGF, and TIMP-2; increased expression of IL-1R and E-selectin; had a transient decrease in IL-6 secretion; and had a transient increase in bFGF secretion. Together, these results show that B3 alters the protein secretion of ASCs