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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]

Biomaterials that support adipogenesis could contribute to tissue engineering therapies to be used as alternatives to traditional methods of tissue reconstruction and regeneration. We have recently shown that hydrogels comprised of urea soluble proteins and polysaccharides extracted from adipose tissue promote preadipocyte differentiation in vitro and adipogenesis in vivo. However, it is not clear if these findings result from the adipose tissue source of the extracts or if the technique isolates adipogenic factors from other tissues. The present study investigates whether the application of this technique to dermis samples would provide adipogenic hydrogels. Extracts from dermis assembled into hydrogels by either temperature or pH mechanisms. Both formulations supported preadipocyte differentiation in vitro and vascularized adipose formation in vivo. The temperature formulation of the gels induced more rapid adipose formation than the pH formulation in vivo. Interestingly, in comparison to our previous studies the dermis derived hydrogels had comparable adipogenic properties to adipose gels in vivo but not in vitro. Further study of these materials could lead to insight of the role of specific matrix properties on adipogenesis., ((c) 2009 Wiley Periodicals, Inc.)

Interactions with the extracellular matrix (ECM) play an important role in regulating cell function. Cells cultured in, or on, three-dimensional ECM recapitulate similar features to those found in vivo that are not present in traditional two-dimensional culture. In addition, both natural and synthetic materials containing ECM components have shown promise in a number of tissue engineering applications. Current materials available for cell culture and tissue engineering do not adequately reflect the diversity of ECM composition between tissues. In this paper, a method is presented for extracting solutions of proteins and glycoproteins from soft tissues and inducing assembly of these proteins into gels. The extracts contain ECM proteins specific to the tissue source with low levels of intracellular molecules. Gels formed from the tissue-derived extracts have nanostructure similar to ECM in vivo and can be used to culture cells as both a thin substrate coating and a thick gel. This technique could be used to assemble hydrogels with varying composition depending upon the tissue source, hydrogels for three-dimensional culture, as scaffolds for tissue engineering therapies, and to study cell-matrix interactions.

The success of many therapies in regenerative medicine requires the ability to control the formation of stable vascular networks within tissues. The formation of new blood vessels, or neovascularization, is mediated, in part, by interactions between endothelial cells (ECs) and insoluble factors in the extracellular microenvironment. These interactions are determined by the chemical, physical, and mechanical properties of the matrix. Understanding how extracellular matrices (ECMs) and synthetic scaffolds influence neovascularization can contribute to the fundamental knowledge of normal and diseased tissue physiology and can be used to guide the design of new therapies. The goal of this review is to provide an overview of the complex role EC-matrix interactions play in neovascularization. A particular emphasis is placed on presenting differences in two subsets of ECM, basement membranes and stromal matrices, and identification of the properties of these matrices that define their biological functions. Attempts to apply information about EC-ECM interactions to enhance vascularization of synthetic materials are presented, and areas in need of further research are identified throughout this review. Our understanding of the role EC-matrix interactions play in neovascularization remains limited, but continued progress in this area could be of significant benefit to the design of clinically applicable engineered tissues.

A number of pathological entities and surgical interventions could benefit from therapeutic stimulation of new blood vessel formation. Although strategies designed for promoting neovascularization have shown promise in preclinical models, translation to human application has met with limited success when angiogenesis is used as the single therapeutic mechanism. While clinical protocols continue to be optimized, a number of exciting new approaches are being developed. Bioengineering has played an important role in the progress of many of these innovative new strategies. In this review, we present a general outline of therapeutic neovascularization, with an emphasis on investigations using engineering principles to address this vexing clinical problem. In addition, we identify some limitations and suggest areas for future research.