Browsing by Author "Zhang, Ying"
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Item Open Access Interstitial engraftment of adipose-derived stem cells into an acellular dermal matrix results in improved inward angiogenesis and tissue incorporation.(J Biomed Mater Res A, 2013-10) Komatsu, Issei; Yang, Jun; Zhang, Ying; Levin, L Scott; Erdmann, D; Klitzman, Bruce; Hollenbeck, Scott TAcellular dermal matrices (ADM) are commonly used in reconstructive procedures and rely on host cell invasion to become incorporated into host tissues. We investigated different approaches to adipose-derived stem cells (ASCs) engraftment into ADM to enhance this process. Lewis rat adipose-derived stem cells were isolated and grafted (3.0 × 10(5) cells) to porcine ADM disks (1.5 mm thick × 6 mm diameter) using either passive onlay or interstitial injection seeding techniques. Following incubation, seeding efficiency and seeded cell viability were measured in vitro. In addition, Eighteen Lewis rats underwent subcutaneous placement of ADM disk either as control or seeded with PKH67 labeled ASCs. ADM disks were seeded with ASCs using either onlay or injection techniques. On day 7 and or 14, ADM disks were harvested and analyzed for host cell infiltration. Onlay and injection techniques resulted in unique seeding patterns; however cell seeding efficiency and cell viability were similar. In-vivo studies showed significantly increased host cell infiltration towards the ASCs foci following injection seeding in comparison to control group (p < 0.05). Moreover, regional endothelial cell invasion was significantly greater in ASCs injected grafts in comparison to onlay seeding (p < 0.05). ADM can successfully be engrafted with ASCs. Interstitial engraftment of ASCs into ADM via injection enhances regional infiltration of host cells and angiogenesis, whereas onlay seeding showed relatively broad and superficial cell infiltration. These findings may be applied to improve the incorporation of avascular engineered constructs.Item Open Access Microfluidic-generated Double Emulsions for Cell Study, Drug Delivery and Particle Therapeutics Fabrication(2015) Zhang, YingDroplet microfluidics is a powerful platform for both fundamental and applied biomedical research. The droplets are small in size with a diameter of 1-300 um. Thus, they could function as a miniaturized environment for quantitative and qualitative analysis. Each droplet composes of water shielded by an immiscible organic shell which enables independent control over different droplets. The large surface to volume ratio of spherical structure allows rapid mass and heat transfer, which could enable more homogeneous chemical reactions. Moreover, since multiple identical droplets could be generated simultaneously, parallel analysis for large amount of samples are possible. The use of microfluidics brings more power to droplet technology. The precise control over the flow allows droplet with preferable size and structure to be generated, which is critical for quantitative analysis, homogeneous chemical reaction as well as some in vivo applications.
Nonetheless, generation of stable, monodispersed and well controlled emulsions to meet specific biological functions are still challenging. First of all, to form more biocompatible W/O/W DE, the microfluidics devices must be patterned with desired surface wettability. W/O emulsion could only form in hydrophobic environment and the O/W emulsions could only form in hydrophilic environment. Differential patterning of the surface wettability to meet the needs are challenging. Second, DE are stabilized by two amphiphilic surfactants, one for the oil phase and the other for the water phase. Selection of appropriate surfactants should hook with specific biological application to ensure stability and biocompatibility. Third, the choice of fluid and contents in the fluid will affect the viscosity and capillary number of interfacial interaction, and eventually influences the droplet formation. The choice of biocompatible medium and buffer must take this into consideration. Fourth, the adoption of emulsions for the specific application requires optimization of the processing techniques in order to meet the needs for final analysis. For instance, control of droplet rupture for content release, modulation of oil phase permeability, quantitative analysis of content with flow cytometry, etc.
In this thesis, we will first demonstrate the design and fabrication of PDMS-based devices for automatic and high-throughput DE formation in Chapter 2. In the following chapters, we will demonstrate the successful adoption of the microfluidics generated DE for different biological applications. In chapter 3, we will illustrate the application of DE as a micro-incubator for cellular studies such genetic circuit behavior and performance in bacterial cells cultured in DE droplets and formation of 3D mammalian cell spheroid. In chapter 4, we will show the successful application of DE as drug carriers for intranasal drug delivery. In chapter 5, we showed the application of microfluidics generated DE as template for microparticle synthesis and the use of these microparticles as therapeutic agents in nucleic acid induced inflammations in autoimmune diseases.
Item Open Access Nanosecond Shock Wave-Induced Surface Acoustic Waves and Fracture at Fluid-Solid(2018) Zhang, YingI investigate the generation and propagation characteristics of leaky Rayleigh waves (LRWs) by a spherical shock wave incident on a glass-water boundary both experimentally and numerically. The maximum tensile stress produced on the solid boundary was attributed to the dynamic interaction between the LRWs and an evanescent wave generated concomitantly along the boundary. The resultant tensile stress field drives the initiation of pre-existing microcracks and their subsequent extension along a circular trajectory, confirmative with the direction of the principal stress on the boundary. We further demonstrated that this unique ring-like fracture, prevalent in damage produced by high-speed impact, can be best described by the Tuler-Butcher criterion for dynamic brittle failure, and the orientation of the ring fracture extension into the solid also follows closely the trajectory of the local maximum tensile stress distribution.
Item Open Access Tissue engraftment of hypoxic-preconditioned adipose-derived stem cells improves flap viability.(Wound Repair Regen, 2012-11) Hollenbeck, Scott T; Senghaas, Annika; Komatsu, Issei; Zhang, Ying; Erdmann, Detlev; Klitzman, BruceAdipose-derived stem cells (ASCs) have the ability to release multiple growth factors in response to hypoxia. In this study, we investigated the potential of ASCs to prevent tissue ischemia. We found conditioned media from hypoxic ASCs had increased levels of vascular endothelial growth factor (VEGF) and enhanced endothelial cell tubule formation. To investigate the effect of injecting rat ASCs into ischemic flaps, 21 Lewis rats were divided into three groups: control, normal oxygen ASCs (10(6) cells), and hypoxic preconditioned ASCs (10(6) cells). At the time of flap elevation, the distal third of the flap was injected with the treatment group. At 7 days post flap elevation, flap viability was significantly improved with injection of hypoxic preconditioned ASCs. Cluster of differentiation-31-positive cells were more abundant along the margins of flaps injected with ASCs. Fluorescent labeled ASCs localized aside blood vessels or throughout the tissue, dependent on oxygen preconditioning status. Next, we evaluated the effect of hypoxic preconditioning on ASC migration and chemotaxis. Hypoxia did not affect ASC migration on scratch assay or chemotaxis to collagen and laminin. Thus, hypoxic preconditioning of injected ASCs improves flap viability likely through the effects of VEGF release. These effects are modest and represent the limitations of cellular and growth factor-induced angiogenesis in the acute setting of ischemia.