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Biomedical subjects

Ruth R Chen

Publications and source records attributed to Ruth R Chen.

4 recordsLinked to original sources

Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation.

PURPOSE: Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. MATERIALS AND METHODS: A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. RESULTS: In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. CONCLUSIONS: Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.

Animals↗

Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb.

PURPOSE: We hypothesized that sustained delivery of vascular endothelial growth factor (VEGF) using a polymer [85:15 poly(lactide-co-glycolide) (PLG)] would enhance angiogenesis and improve perfusion of ischemic tissue. METHODS: C57BL/6J mice (n = 20/group) underwent unilateral hind limb ischemia surgery and were randomized to groups of no scaffold implantation (0-Implant), unloaded scaffold implantation (Empty-PLG), or implantation of scaffolds incorporating 3 microg of VEGF165 (PLG-VEGF). Endpoints included laser Doppler perfusion imaging (LDPI, ischemic/nonischemic limb, %), local vessel counts, immunohistochemistry for CD31, and alpha-smooth muscle actin. In vitro release kinetics of VEGF from PLG was also measured. RESULTS: PLG-VEGF resulted in improved lower extremity perfusion vs. controls as measured by LDPI% at 7, 14, 21, and 28 days (p < 0.05). PLG-VEGF was associated with significantly greater percentage of vessels staining for CD31 and alpha-smooth muscle actin compared to the Empty-PLG or 0-Implant (p < 0.05 for both). CONCLUSIONS: The PLG-VEGF scaffolds resulted in sustained VEGF delivery, improved tissue perfusion, greater capillary density, and more mature vasculature compared to the controls. The sustained-release PLG polymer vehicle is a promising delivery system for therapeutic neovascularization applications.

Actins↗

The influence of microchannels on neurite growth and architecture.

Microchannels were produced using a photolithographic technique to pattern polyimide walls (11 microm in height and 20-60 microm in width) onto a planar glass substrate. PC12 cells were seeded onto patterned surfaces. After 3 days of culture in NGF supplemented medium cells were viable and extended neurites. Culture in microchannels influenced the direction of neurite growth (theta Orientation) and the complexity of PC12 cell architecture including neurite length (L(Neurite)), the number of neurites emerging per cell (N(Neurites)), and the angle at which neurites emerged from the cell soma (theta Soma). In microchannels neurites oriented parallel to channel walls and the complexity of neuronal architecture was reduced. Both of these effects were strongest for cells located in channels 20-30 microm wide. Within each channel the magnitude of the effect on orientation and architecture was inversely proportional to the distance of the soma from the channel wall. Microtubule and actin filament mobility within the cytoplasm may underly effect on neurite orientation and cell architecture. By manipulating channel width the overall direction of neurite growth and the complexity of neuronal architecture was controlled. Results from these studies will be applied towards the development of biomaterials for microfluidic platforms and drug discovery studies and in neural regeneration research-two applications that would be significantly improved given the ability to control neurite orientation and the complexity of neuronal architecture.

Animals↗

Polymeric growth factor delivery strategies for tissue engineering.

PURPOSE: Tissue engineering seeks to replace and regrow damaged or diseased tissues and organs from either cells resident in the surrounding tissue or cells transplanted to the tissue site. The purpose of this review is to present the application of polymeric delivery systems for growth factor delivery in tissue engineering. METHODS: Growth factors direct the phenotype of both differentiated and stem cells, and methods used to deliver these molecules include the development of systems to deliver the protein itself, genes encoding the factor, or cells secreting the factor. RESULTS: Results in animal models and clinical trials indicate that these approaches may be successfully used to promote the regeneration of numerous tissue types. CONCLUSIONS: Controlling the dose, location, and duration of these factors through polymeric delivery strategies will dictate their utility in tissue regeneration.

Animals↗