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Abstract: Chronic exposure to reducing sugars due to diabetes, aging, and diet can permanently modify extracellular matrix (ECM) proteins. This non-enzymatic glycosylation, or glycation, can lead to the formation of advanced glycation end products (AGE) and crosslinking of the ECM. This study investigates the effects of glycation on the properties of type I collagen gels. Incubation with glucose-6-phopshate (G6P), a reducing sugar that exhibits similar but more rapid glycation than glucose, modified the biological and mechanical properties of collagen gels. Measures of AGE formation that correlate with increased complications in people with diabetes, including collagen autofluorescence, crosslinking, and resistance to proteolytic degradation, increased with G6P concentration. Rheology studies showed that AGE crosslinking increased the shear storage and loss moduli of type I collagen gels. Fibroblasts cultured on glycated collagen gels proliferated more rapidly than on unmodified gels, but glycated collagen decreased fibroblast invasion. These results show that incubation of type I collagen gels with G6P increases clinically relevant measures of AGE formation and that these changes altered cellular interactions. These gels could be used as in vitro models to study ECM changes that occur in diabetes and aging. [Copyright &y& Elsevier]

Abstract: Biomaterials that induce adipogenesis may ultimately serve as alternatives to traditional tissue reconstruction and regeneration techniques. In addition, these materials can provide environments for studying factors that regulate adipogenesis. The present study investigates the potential of adipose-derived matrices to induce adipogenesis in vitro and in vivo. Solutions containing basement membrane proteins and growth factors were extracted from subcutaneous adipose tissue. These extracts could be induced to form gels by either incubating the solutions at 37°C or adjusting the pH to 4.0. The adipose extracts promoted rapid preadipocyte aggregation and formation of lipid-loaded colonies in vitro. Differentiation on adipose-derived gels was greater than tissue culture dishes and the tumor-derived product Matrigel™ (p <0.05). Significant adipose formation was observed when adipose-derived gels were implanted around a rat epigastric pedicle bundle. Adipose levels in these gels were significantly greater than Matrigel™ (p <0.05). The duration of adipose formation depended on the mechanism for gelling the solutions, with acid gelled matrices having greater adipose levels at 6 weeks than temperature gelled matrices. These adipose-derived hydrogels promote rapid adipogenesis in vitro and in vivo. They may lead to new materials for adipose tissue engineering, and provide an environment for studying cell–matrix interactions in adipogenesis. [Copyright &y& Elsevier]

Abstract: Background: Therapeutic neovascularization using high growth factor concentrations may lead to transient vessel formation and abnormal microvascular structure. The goal of this study was to quantify temporal and concentration effects of fibroblast growth factor-1 (FGF-1) on the persistence and morphology of microvascular networks. Methods: Endothelial cells were incubated in suspension culture forming aggregates that were embedded in fibrin glue (FG) and stimulated with varying concentrations of FGF-1 with of heparin. Capillary networks formed were quantified for 21 days. Results: High FGF-1 concentrations resulted in rapid and intense sprout formation, with excessive branching. At later times, these vessels regressed, with cellular debris in former vessel locations. At later times, the 1-ng/mL group surpassed the high concentration groups with continuous sprout growth and complete FG vascularization by 23 days. Conclusion: Sustained low levels of FGF-1 maintained a persistent microvascular network response, whereas higher levels resulted in abnormal phenotype followed by vessel regression. [Copyright &y& Elsevier]