Nanoplatelet

My current research focuses on manipulating materials at the nanoscale in order to use them for applications in furthering human health. To achieve this, I have been utilizing biologically derived materials to synthesize nanoparticles. Nanoparticles have a wide variety of applications in imaging the body and in treating diseases. The nanoplatelets in this image are one example of the types of nanoparticles that I have synthesized. Achieving unique shapes like this at the nanoscale provides an understanding of how different materials interact with each other, and these shapes can even open new doors for the applications of nanomaterials.Ope

Personalized absorbable gastrointestinal stents for intestinal fistulae and perforations

Gastrointestinal (GI) tract perforations and obstructions are relatively frequent surgical emergencies, are potentially life-threatening, and can occur from several different sources. In general, treatment requires urgent surgical repair or resection and at times can lead to further complications. Currently available stents are non-absorbable, are manufactured in a narrow size range, and/or are limited to usage in locations that are accessible for endoscopic removal post-healing. The use of 3D-printed bioresorbable polymeric stents will provide patients with a stent that can prevent leakage, is tailored specifically to their geometry, will degrade with time to eliminate the need for further surgeries for stent removal post-healing, and will be usable in locations that are not endoscopically accessible. This project focused on the characterization of polycaprolactone-polydioxanone (PCL-PDO) composites for use in a bioresorbable gastrointestinal stent. Dynamic Mechanical Analysis (DMA) tests were conducted to separately analyze the effects of composition, the filament formation process, and physiological temperature on the PCL-PDO material properties. The proposed stent design was then modelled using computer-aided design, and Finite Element Analysis (FEA) was used to simulate the effects of physiologically relevant forces on stent integrity. The presence of hydrolysable ester bonds was confirmed using FTIR spectroscopy, and composite morphology was examined with scanning electron microscopy. In vitro studies were used to evaluate the biocompatibility of the polymer composite, finding that the PCL:PDO filament had no negative impact on cell viability over a period of 48 hours, and in fact was conducive to cell proliferation over a period of 3 days. PCL-PDO stents were then 3D-printed and placed in vivo in a pig model, and histological evaluation was used to determine the safety of these stents. Further analyses were conducted through stent placement in ex vivo pig intestines

Copper-Catalyzed Syntheses of Pyrene-Pyrazole Pharmacophores and Structure Activity Studies for Tubulin Polymerization

Tubulin polymerization is critical in mitosis process, which regulates uncontrolled cell divisions. Here, we report a new class of pyrene-pyrazole pharmacophore (PPP) for targeting microtubules. Syntheses of seven pyrenyl-substituted pyrazoles with side-chain modification at N-1 and C-3 positions of the pyrazole ring were accomplished from alkenyl hydrazones via C–N dehydrogenative cross-coupling using copper catalyst under aerobic condition. Tubulin polymerization with PPPs was investigated using docking and biological tools to reveal that these ligands are capable of influencing microtubule polymerization and their interaction with α-, β-tubulin active binding sites, which are substituent specific. Furthermore, cytotoxicity response of these PPPs was tested on cancer cells of different origin, such as MCF-7, MDA-MB231, and C32, and also noncancerous normal cells, such as MCF-10A. All newly synthesized PPPs showed excellent anticancer activities. The anticancer activities and half-maximal inhibitory concentration (IC₅₀) values of all PPPs across different cancer cell lines (MCF-7, MDA-MB231, and C32) have been demonstrated. 1,3-Diphenyl-5-(pyren-1-yl)-1<i>H</i>-pyrazole was found to be best among all other PPPs in killing significant population of all of the cancerous cell with IC₅₀ values 1 ± 0.5, 0.5 ± 0.2, and 5.0 ± 2.0 μM in MCF-7, MDA-MB231, and C32 cells, respectively

Zeolite-Loaded Alginate-Chitosan Hydrogel Beads as a Topical Hemostat

Hemorrhage is the leading cause of preventable death after a traumatic injury. Commercial hemostatic agents exist, but have various disadvantages including high cost, short shelf-lives, or secondary tissue damage. Polymer hydrogels provide a promising platform for the use of both biological and mechanical mechanisms to accelerate natural hemostasis and control hemorrhage. The goal of this work was to develop hydrogel particles composed of chitosan and alginate and loaded with zeolite in order to stop blood loss by targeting multiple hemostatic mechanisms. Several ii particle compositions were synthesized and then characterized through swelling studies, particle sizing, Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR). The in vitro interactions of the particles were evaluated through coagulation, degradation, platelet aggregation, and cytotoxicity studies. The results indicate that 4% alginate, 1% chitosan, 4% zeolite-loaded hydrogel beads can significantly reduce time to coagulation and increase platelet aggregation in vitro. Future research can look into the efficacy of these particles in vivo

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel

Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating the levels of 59 proteins in the plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, and developed a new equation for prediction of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types. Trauma patients had significantly upregulated proteins associated with immune activation (IL-23, MIP-5), immunosuppression (IL-10) and pleiotropic cytokines (IL-29, IL-6). A high ratio of IL-29 to IL-10 was identified as a new predictor of survival in less severe patients with ROC area of 0.933. Combining machine learning with statistical modeling we developed an equation ("VIPER") that could predict survival with ROC 0.966 in less severe patients and 0.8873 for all patients from a five analyte panel (IL-6, VEGF-A, IL-21, IL-29, and IL-10). Furthermore, we also identified three increased proteins (MIF, TRAIL, IL-29) and three decreased proteins (IL-7, TPO, IL-8) that were the most important in distinguishing a trauma blood profile. Biologic sex altered phenotype with IL-8 and MIF being lower in healthy women, but higher in female trauma patients when compared to male counterparts. This work identifies new responses to injury that may influence systemic immune dysfunction, serving as targets for therapeutics and immediate clinical benefit in identifying at-risk patients.Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating the levels of 59 proteins in the plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, and developed a new equation for prediction of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types. Trauma patients had significantly upregulated proteins associated with immune activation (IL-23, MIP-5), immunosuppression (IL-10) and pleiotropic cytokines (IL-29, IL-6). A high ratio of IL-29 to IL-10 was identified as a new predictor of survival in less severe patients with ROC area of 0.933. Combining machine learning with statistical modeling we developed an equation ("VIPER") that could predict survival with ROC 0.966 in less severe patients and 0.8873 for all patients from a five analyte panel (IL-6, VEGF-A, IL-21, IL-29, and IL-10). Furthermore, we also identified three increased proteins (MIF, TRAIL, IL-29) and three decreased proteins (IL-7, TPO, IL-8) that were the most important in distinguishing a trauma blood profile. Biologic sex altered phenotype with IL-8 and MIF being lower in healthy women, but higher in female trauma patients when compared to male counterparts. This work identifies new responses to injury that may influence systemic immune dysfunction, serving as targets for therapeutics and immediate clinical benefit in identifying at-risk patients

A hybrid semiconducting organosilica-based O2 nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy

10.1038/s41467-020-20860-3Nature Communications12152