Event
Bioengineering Seminar Series: Graduate Research
Friday, May 6, 2011
11:00 a.m.
Room 1200, Jeong H. Kim Engineering Building
Professor Sameer Shah
sameer@umd.edu
Graduate Research: Laura Hyland, Alek Nacev, Jeremiah Wierwille, and Veemoon Wei Yu
Chitosan and Alginate Scaffolds for Tissue Engineering
Laura Hyland
Networks made from chitosan and alginate have been utilized as prospective tissue engineering scaffolds due to material biocompatibility and degradability. Calcium (Ca2+) is often added to these networks as a modifier for mechanical strength enhancement. In this work, we tested the effect of adding another modifier, chondroitin, an anionic polysaccharide to chitosan/alginate mixtures with three different starting mass fractions: 2%, 3% and 5%. We further tested the effect of which of the two modifiers, Ca2+and chondroitin, is added first. To this end, three types of networks were prepared: A, B and C. It was found that both the addition of chondroitin and larger polysaccharide concentrations significantly increased the mechanical strength of chitosan/alginate networks. Network porosity, density and pore size were slightly dependent on total polysaccharide concentration. Small angle neutron scattering (SANS) revealed that addition of Ca2+ and chondroitin modifiers increased fiber compactness and thickness respectively, which correlates with improved network mechanical properties.
Dynamic Magnetic Shifting: Simulating the Targeting of Insulated Breast Cancer Liver Metastases
Alek Nacev
A nanoparticle delivery system termed Dynamic Magnetic Shift (DMS)could potentially more effectively treat metastatic disease by equilibrating therapeutic magnetic nano-particles throughout tumors. To evaluate the feasibility of DMS, liver histological sections from breast cancer autopsy cases were studied to measure vessel number, size, and spatial distribution in both metastatic tumors and normal tissue. Consistent with prior studies,6 normal tissue had a higher vessel density, a vessel to nuclei ratio of 0.48 ± 0.14, while tumor tissue had a ratio of 0.13 ± 0.07. For tumors, increased distances from cells to their nearest blood vessel was found (average = 43.8 μm; maximum = 287 μm), compared to normal cells (average = 5.3 μm; maximum = 67.8 μm). Greater distances of tumor cells from blood vessels implies that systemically delivered nanoparticles eluting from vessels into surrounding tissue, for the purpose of delivering chemotherapeutic agents, would preferentially dose healthy instead of cancerous cells. Numerical simulations of magnetically driven particle transport based on this autopsy data indicate that DMS would improve nanoparticle concentration in hypovascular regions of metastases, increasing the time-averaged nanoparticle concentration delivered to the tumor for magnetic actuation vs. diffusion alone by 1.86 fold, and increasing the maximum concentration over time by 1.89 fold. Thus DMS may prove useful in allowing therapeutic nanoparticles to reach poorly vascularized regions of metastatic tumors that they would not access by diffusion alone.
In Vivo Imaging of Kidney Microcirculation Using Doppler Optical Coherence Tomography
Jeremiah Wierwille
Doppler optical coherence tomography (DOCT) is an extension of OCT that detects phase shifts in backscattered light resulting from contact with moving scatterers. DOCT enables detection of blood flow in vivo. DOCT is potentially very useful in a clinical setting having high-resolution (~10 μm) and the ability to be miniaturized into handheld devices or endoscopic probes. While the imaging depth of DOCT is limited to ~2mm, we have shown that this penetration is sufficient for imaging of the kidney microcirculation in the superficial cortical region.
To image the kidney in vivo, Munich-Wistar rats were anesthetized and the kidney exposed beneath a swept-source microscope (λ0=1310 nm, dλ=100 nm). Many glomeruli were easily identified by scanning the surface of the kidney, capturing 3D DOCT volumetric data sets at each location. The Doppler signal at each en face plane was integrated over its respective area as a measure of glomerular blood flow. Flow histograms were also extracted for each distinct Doppler signal that could be isolated. To test changes in physiological blood flow, mannitol and angiotensin II were administered intravenously to induce increases and decreases in glomerular flow, respectively.
Individual blood flow patterns were readily visible by DOCT. 3D reconstructions of these images provided an enhanced visualization of the blood flow throughout the capillary network in the glomeruli. An increase in glomerular blood flow was observed following injection of mannitol and a decrease was observed following injection of angiotensin II. These observations were confirmed to be significant after calculating and comparing the glomerular blood flow affected by each drug.
In conclusion, DOCT is able to determine different directional flow patterns in glomerular capillaries and to detect changes in these blood flow patterns in real-time. Thus, these results suggest that DOCT may be helpful in monitoring the status of kidney microcirculation in the clinical setting to help evaluate and predict post-transplant graft function.
Paper-based Biosensing with Surface Enhanced Resonance Spectroscopy
Veemoon Wei Yu
Highly SERS-active substrates have been fabricated for molecular analysis by ink-jet printing nanoparticles onto paper. Combined with the power of Surface Enhanced Raman Spectroscopy, these substrates constitute a simple, low-cost but extremely sensitive analysis tool. By modifying the paper surface chemistry, microfluidic techniques can also be incorporated. The printed substrate has the ability to detect as little as 10 attomoles of a test analyte using a portable, low power Raman spectroscopy system.
