The vascularization of tissue constructs remains a major challenge in regenerative medicine, as the diffusional supply of oxygen can support only 100-200 mum thick layers of viable tissue. The formation of a mature and functional vascular network requires communication between endothelial cells (ECs) and smooth muscle cells (SMCs). Potential sources of these cells that involve noninvasive methodologies are required for numerous applications including tissue-engineered vascular grafts, myocardial ischemia, wound healing, plastic surgery, and general tissue-engineering applications. Human embryonic stem cells (hESCs) can be an unlimited source of these cells. They can be expanded in vitro in an undifferentiated state without apparent limit, and hES-derived cells can be created in virtually unlimited amounts for potential clinical uses. Recently, vascular progenitor cells as well as endothelial and smooth muscle cells have been isolated from hESCs. Full Article

Modification of dextran backbone allows the development of a hydrogel with specific characteristics. To enhance their functionality for tissue-engineered scaffolds, a series of dextran-based macromers was synthesized by incorporating various functional groups, including allyl isocyanate (Dex-AI), ethylamine (Dex-AE), chloroacetic acid (Dex-AC), or maleic-anhydride (Dex-AM) into dextrans. The dextran-based biodegradable hybrid hydrogels are developed by integrating polyethylene glycol diacrylate (PEGDA). To explore the effect of different derivatives on hydrogel properties, three different ratios of Dex/PEGDA are examined: low (20/80), medium (40/60), and high (60/40). Differences in physical and biological properties of the hydrogels are found, including swelling, degradation rate, mechanics, crosslinking density, biocompatibility (in vitro and in vivo), and vascular endothelial growth factor release. The results also indicate that the incorporation of amine groups into dextran gives rise to hydrogels with better biocompatible and release properties. We, therefore, conclude that the incorporation of different functional groups affects the fundamental properties of a dextran-based hydrogel network, and that amine groups are preferred to generate hydrogels for biomedical use. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. Full Article

Vascular diseases are a major threat to human health nowadays. While current treatments can cure some vascular diseases, their beneficial effects are only temporary; vascular regeneration holds the promise of permanent, effective treatments for many vascular diseases. Stem cells and endothelial progenitor cells can differentiate into vascular lineages and therefore have the potential to repair vascular systems. However, engineering appropriate microenvironments that will allow cell maturation and delivery remains the major challenge to the successful implementation of this treatment. This review introduces the cells that are being studied for vascular differentiation and regeneration; we then consider recent approaches to engineering microenvironments, including proper signaling cues and biodegradable scaffolds that will guide the development of these cells into vessels suitable for cell-based vascular therapy. Full Article

Engineering vascularized tissue constructs remains a major problem in regenerative medicine. The formation of such a microvasculature--like the vasculogenesis in early embryogenesis that it closely resembles--is guided by biochemical and biophysical cues, such as growth factors, extracellular matrix proteins, hypoxia, and hydrodynamic shear. As they undergo spontaneous and directed vascular differentiation, human embryonic stem cells can be used as a model system to explore central issues in engineering vascularized tissue constructs and, potentially, to elucidate vasculogenic and angiogenic mechanisms involved in such vascular diseases as limb and cardiac ischemia. Because the conventional spontaneous differentiation approach can only isolate small quantities of vascular cells, recent efforts have sought to develop controlled approaches, including the development of three-dimensional scaffolds to reengineer the microenvironments of early embryogenesis. This review focuses on emerging approaches to deriving and directing vasculatures from human embryonic stem cells and efforts to engineer 3D vasculatures from such derivatives. Full Article