@article{mantooth_hancock_thompson_varghese_meritet_vrabel_hu_zaharoff_2024, title={Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics}, volume={10}, ISSN={["2373-9878"]}, url={https://doi.org/10.1021/acsbiomaterials.3c01580}, DOI={10.1021/acsbiomaterials.3c01580}, abstractNote={Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.}, number={2}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Mantooth, Siena M. and Hancock, Asher M. and Thompson, Peter M. and Varghese, P. J. George and Meritet, Danielle M. and Vrabel, Maura R. and Hu, Jingjie and Zaharoff, David A.}, year={2024}, month={Jan}, pages={905–920} } @article{varghese_zhao_chen_hu_2024, title={Chitosan-nanoclay embolic material for catheter-directed arterial embolization}, volume={1}, ISSN={["1552-4965"]}, url={https://doi.org/10.1002/jbm.a.37670}, DOI={10.1002/jbm.a.37670}, abstractNote={Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology. It is used for the deliberate occlusion of blood vessels for the treatment of disease or injured vasculature, including vascular malformation and malignant/benign tumors. Here, we introduce a gel embolic agent comprising chitosan nanofibers and nanoclay with excellent catheter injectability and tunable mechanical properties for embolization. The properties of the gel were optimized by varying the ratio between each individual component and also adjusting the total solid content. The rheological studies confirm the shear thinning property and gel nature of the developed gel as well as their recoverability. Injection force was measured to record the force required to pass the embolic gel through a clinically relevant catheter, evaluating for practicality of hand-injection. Theoretical predicted injection force was calculated to reduce the development time and to enhance the physician's experience. The stability of occlusion was also tested in vitro by monitoring the pressure required to displace the gel. The engineered gels exhibited sterility, hemocompatibility and cell biocompatibility, highlighting their potential for transcatheter embolization.}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, author={Varghese, P. J. George and Zhao, Keren and Chen, Peng and Hu, Jingjie}, year={2024}, month={Jan} } @article{zhao_varghese_chen_hu_2024, title={Developing a transcatheter injectable nanoclay- alginate gel for minimally invasive procedures}, volume={152}, ISSN={["1878-0180"]}, url={https://doi.org/10.1016/j.jmbbm.2024.106448}, DOI={10.1016/j.jmbbm.2024.106448}, abstractNote={Shear-thinning materials have held considerable promise as embolic agents due to their capability of transition between solid and liquid state. In this study, a laponite nanoclay (NC)/alginate gel embolic agent was developed, characterized, and studied for transcatheter based minimally invasive procedures. Both NC and alginate are biocompatible and FDA-approved. Due to electrostatic interactions, the NC/alginate gels exhibit shear-thinning properties that are desirable for transcatheter delivery. The unique shear-thinning nature of the NC/alginate gel allows it to function as a fluid-like substance during transcatheter delivery and as a solid-like embolic agent once deployed. To ensure optimal performance and safety in clinical applications, the rheological characteristics were thoroughly investigated to optimize the mechanical properties of the NC/alginate gel, including storage modulus, yield stress/strain, and thixotropy. To improve physicians' experience and enhance the predictability of gel delivery, a combination of experimental and theoretical approaches was used to assess the injection force required for successful delivery of the gel through clinically employed catheters. Overall, NC/alginate gel exhibited excellent stability and tunable injectability by optimizing the composition of each component. These findings highlight the gel's potential as a robust embolic agent for a wide range of minimally invasive procedures.}, journal={JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS}, author={Zhao, Keren and Varghese, P. J. George and Chen, Peng and Hu, Jingjie}, year={2024}, month={Apr} } @article{uzonwanne_navabi_obayemi_hu_salifu_ghahremani_ndahiro_rahbar_soboyejo_2022, title={Triptorelin-functionalized PEG-coated biosynthesized gold nanoparticles: Effects of receptor-ligand interactions on adhesion to triple negative breast cancer cells}, volume={4}, url={http://dx.doi.org/10.1016/j.bioadv.2022.212801}, DOI={10.1016/j.bioadv.2022.212801}, abstractNote={This paper presents the results of an experimental and computational study of the adhesion of triptorelin-conjugated PEG-coated biosynthesized gold nanoparticles (GNP-PEG-TRP) to triple-negative breast cancer (TNBC) cells. The adhesion is studied at the nanoscale using a combination of atomic force microscopy (AFM) experiments and molecular dynamics (MD) simulations. The AFM measurements showed that the triptorelin-functionalized gold nanoparticles (GNP-TRP and GNP-PEG-TRP) have higher adhesion to triple-negative breast cancer cells (TNBC) than non-tumorigenic breast cells. The increased adhesion of GNP-TRP and GNP-PEG-TRP to TNBC is also attributed to the overexpression of LHRH receptors on the surfaces of both TNBC. Finally, the molecular dynamics model reveals insights into the effects of receptor density, molecular configuration, and receptor-ligand docking characteristics on the interactions of triptorelin-functionalized PEG-coated gold nanoparticles with TNBC. A three to nine-fold increase in the adhesion is predicted between triptorelin-functionalized PEG-coated gold nanoparticles and TNBC cells. The implications of the results are then discussed for the specific targeting of TNBC.}, journal={Biomaterials Advances}, publisher={Elsevier BV}, author={Uzonwanne, Vanessa O. and Navabi, Arvand and Obayemi, John D. and Hu, Jingjie and Salifu, Ali A. and Ghahremani, Shahnaz and Ndahiro, Nelson and Rahbar, Nima and Soboyejo, Winston}, year={2022}, month={Apr}, pages={212801} } @article{onwudiwe_hu_obayemi_uzonwanne_ani_nwazojie_onyekanne_ezenwafor_odusanya_soboyejo_2021, title={Actin cytoskeletal structure and the statistical variations of the mechanical properties of non-tumorigenic breast and triple-negative breast cancer cells}, volume={119}, url={https://doi.org/10.1016/j.jmbbm.2021.104505}, DOI={10.1016/j.jmbbm.2021.104505}, abstractNote={This paper presents the results of a study of the actin cytoskeletal structures and the statistical variations in the actin fluorescence intensities and viscoelastic properties of non-tumorigenic breast cells and triple-negative breast cancer cells at different stages of tumor progression. The variation in the actin content of the cell cytoskeletal structures is shown to be consistent with the viscoelastic properties of the cell as it progresses from non-tumorigenic to more metastatic states. The corresponding viscoelastic properties of the nuclei and the cytoplasm (Young's moduli, viscosities, and relaxation times) of the cells are also measured using Digital Image Correlation (DIC) and shear assay techniques. These properties are shown to exhibit statistical variations that are well characterized by normal distributions. The changes in the mean properties of individual cancer cells are tested using Fisher pairwise comparisons and the analysis of variance (ANOVA). The implications of the results are then discussed for the development of shear assay techniques and mechanical biomarkers for the detection of triple-negative breast cancer at different stages of tumor progression.}, journal={Journal of the Mechanical Behavior of Biomedical Materials}, publisher={Elsevier BV}, author={Onwudiwe, Killian and Hu, Jingjie and Obayemi, John and Uzonwanne, Vanessa and Ani, Chukwuemeka and Nwazojie, Chukwudalu and Onyekanne, Chinyerem and Ezenwafor, Theresa and Odusanya, Olushola and Soboyejo, Winston}, year={2021}, month={Jul}, pages={104505} } @article{onwudiwe_obayemi_hu_oparah_onyekanne_nwazojie_aina_uzonwanne_salifu_soboyejo_2021, title={Investigation of creep properties and the cytoskeletal structures of non-tumorigenic breast cells and triple-negative breast cancer cells}, volume={110}, ISSN={["1552-4965"]}, url={http://dx.doi.org/10.1002/jbm.a.37348}, DOI={10.1002/jbm.a.37348}, abstractNote={This article presents the correlation of creep and viscoelastic properties to the cytoskeletal structure of both tumorigenic and non-tumorigenic cells. Unique shear assay and strain mapping techniques were used to study the creep and viscoelastic properties of single non-tumorigenic and tumorigenic cells. At least 20 individual cells, three locations per cell, were studied. From the results, lower densities in the volume of actin, and keratin 18 structures were observed with the progression of cancer and were correlated to the increased creep rates and reduced mechanical properties (Young's moduli and viscosities) of tumorigenic (MDA-MB-231) cells. The study reveals significant differences between the creep and viscoelastic properties of non-tumorigenic breast cells versus tumorigenic cells. The variations in the creep strain rates are shown to be well characterized by lognormal distributions, while the statistical variations in the viscoelastic properties are well-described by normal distributions. The implications of the results are discussed for the study of discrete cell behaviors, strain and viscoelastic responses of the cell, and the role of cell cytoskeleton in the onset and progression of cancers.}, number={5}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A}, publisher={Wiley}, author={Onwudiwe, Killian and Obayemi, John and Hu, Jingjie and Oparah, Josephine and Onyekanne, Chinyerem and Nwazojie, Chukwudalu and Aina, Toyin and Uzonwanne, Vanessa and Salifu, Ali and Soboyejo, Winston}, year={2021}, month={Dec} } @article{albadawi_zhang_altun_hu_jamal_ibsen_tanner_mitragotri_oklu_2021, title={Percutaneous liquid ablation agent for tumor treatment and drug delivery}, volume={13}, url={https://doi.org/10.1126/scitranslmed.abe3889}, DOI={10.1126/scitranslmed.abe3889}, abstractNote={An ionic liquid formulation ablates tumors, uniformly distributes drugs in the ablation zone, and has synergistic effects with chemotherapy. Advances in ablation For individuals with hepatocellular carcinoma, percutaneous locoregional therapies can extend the time to liver transplantation. Albadawi et al. developed an ionic liquid–ablative agent named LATTE that could be locally injected into rat, rabbit, and pig livers in vivo under imaging guidance. LATTE coformulated with the chemotherapy drug doxorubicin injected into tumors in rat and rabbit livers ablated the desired regions, uniformly distributed the drug, and could also ablate human liver tumor tissue samples ex vivo. Results support the use of LATTE for percutaneous ablation of solid tumors. Percutaneous locoregional therapies (LRTs), such as thermal ablation, are performed to limit the progression of hepatocellular carcinoma (HCC) and offer a bridge for patients waiting for liver transplantation. However, physiological challenges related to tumor location, size, and existence of multiple lesions as well as safety concerns related to potential thermal injury to adjacent tissues may preclude the use of thermal ablation or lead to its failure. Here, we showed a successful injection of an ionic liquid into tissue under image guidance, ablation of tumors in response to the injected ionic liquid, and persistence (28 days) of coinjected chemotherapy with the ionic liquid in the ablation zone. In a rat HCC model, the rabbit VX2 liver tumor model, and 12 human resected tumors, injection of the ionic liquid led to consistent tumor ablation. Combining the ionic liquid with the chemotherapy agent, doxorubicin, resulted in synergistic cytotoxicity when tested with cultured HCC cells and uniform drug distribution throughout the ablation zone when percutaneously injected into liver tumors in the rabbit liver tumor model. Because this ionic liquid preparation is simple to use, is efficacious, and has a low cost, we propose that this new LRT may bridge more patients to liver transplantation.}, number={580}, journal={Science Translational Medicine}, publisher={American Association for the Advancement of Science (AAAS)}, author={Albadawi, Hassan and Zhang, Zefu and Altun, Izzet and Hu, Jingjie and Jamal, Leila and Ibsen, Kelly N. and Tanner, Eden E. L. and Mitragotri, Samir and Oklu, Rahmi}, year={2021}, month={Feb} } @article{hu_albadawi_zhang_salomao_gunduz_rehman_d’amone_mayer_omenetto_oklu_2021, title={Silk Embolic Material for Catheter‐Directed Endovascular Drug Delivery}, volume={11}, url={http://dx.doi.org/10.1002/adma.202106865}, DOI={10.1002/adma.202106865}, abstractNote={Embolization is a catheter‐based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. A novel silk‐based embolic material (SEM) that is developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics is reported. Natural silk is processed into fibroin proteins of varying lengths and is combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 μm in diameter at lengths >100 cm. SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs worldwide, demonstrate a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolize porcine arteries without recanalization and lead to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, it is shown that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next‐generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors.}, journal={Advanced Materials}, publisher={Wiley}, author={Hu, Jingjie and Albadawi, Hassan and Zhang, Zefu and Salomao, Marcela A. and Gunduz, Seyda and Rehman, Suliman and D’Amone, Luciana and Mayer, Joseph L. and Omenetto, Fiorenzo and Oklu, Rahmi}, year={2021}, month={Nov}, pages={2106865} } @article{hu_altun_zhang_albadawi_salomao_mayer_hemachandra_rehman_oklu_2020, title={Bioactive‐Tissue‐Derived Nanocomposite Hydrogel for Permanent Arterial Embolization and Enhanced Vascular Healing}, url={https://doi.org/10.1002/adma.202002611}, DOI={10.1002/adma.202002611}, abstractNote={Transcatheter embolization is a minimally invasive procedure that uses embolic agents to intentionally block diseased or injured blood vessels for therapeutic purposes. Embolic agents in clinical practice are limited by recanalization, risk of non‐target embolization, failure in coagulopathic patients, high cost, and toxicity. Here, a decellularized cardiac extracellular matrix (ECM)‐based nanocomposite hydrogel is developed to provide superior mechanical stability, catheter injectability, retrievability, antibacterial properties, and biological activity to prevent recanalization. The embolic efficacy of the shear‐thinning ECM‐based hydrogel is shown in a porcine survival model of embolization in the iliac artery and the renal artery. The ECM‐based hydrogel promotes arterial vessel wall remodeling and a fibroinflammatory response while undergoing significant biodegradation such that only 25% of the embolic material remains at 14 days. With its unprecedented proregenerative, antibacterial properties coupled with favorable mechanical properties, and its superior performance in anticoagulated blood, the ECM‐based hydrogel has the potential to be a next‐generation biofunctional embolic agent that can successfully treat a wide range of vascular diseases.}, journal={Advanced Materials}, author={Hu, Jingjie and Altun, Izzet and Zhang, Zefu and Albadawi, Hassan and Salomao, Marcela A. and Mayer, Joseph L. and Hemachandra, L. P. Madhubhani P. and Rehman, Suliman and Oklu, Rahmi}, year={2020}, month={Aug} } @article{altun_hu_albadawi_zhang_salomao_mayer_jamal_oklu_2020, title={Blood‐Derived Biomaterial for Catheter‐Directed Arterial Embolization}, url={https://doi.org/10.1002/adma.202005603}, DOI={10.1002/adma.202005603}, abstractNote={Vascular embolization is a life‐saving minimally invasive catheter‐based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood‐derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra‐arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point‐of‐care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.}, journal={Advanced Materials}, author={Altun, Izzet and Hu, Jingjie and Albadawi, Hassan and Zhang, Zefu and Salomao, Marcela A. and Mayer, Joseph L. and Jamal, Leila and Oklu, Rahmi}, year={2020}, month={Dec} } @article{wang_hu_sheth_oklu_2020, title={Emerging embolic agents in endovascular embolization: an overview}, volume={2}, url={https://doi.org/10.1088/2516-1091/ab6c7d}, DOI={10.1088/2516-1091/ab6c7d}, abstractNote={Endovasular embolization treats diseased and malfunctioned vasculature through a minimally invasive approach that significantly benefits patients. Advances in engineering and materials science have contributed to novel generations of embolic materials that addresses challenges existed in clinically used agents. In this review, we discuss the clinically available embolic agents, their formulations and applications. Additionally, we examine materials in development for embolization, and emphasize the challenges during the process of transitioning from basic science to translational applications in this field.}, number={1}, journal={Progress in Biomedical Engineering}, publisher={IOP Publishing}, author={Wang, Courtney Y and Hu, Jingjie and Sheth, Rahul A and Oklu, Rahmi}, year={2020}, month={Feb}, pages={012003} } @misc{foundations of biomaterials engineering by maria cristina tanzi, silvia farè, and gabriele candiani_2020, url={https://www.cambridge.org/core/journals/mrs-bulletin/article/foundations-of-biomaterials-engineering-by-maria-cristina-tanzi-silvia-fare-and-gabriele-candiani-academic-press-2019-572-pages-9995-ebook-9799-isbn-9780081010341-ebook-isbn-9780128094594/0D032065A045E7CA68F5D5DC69596A1E}, DOI={https://doi.org/10.1557/mrs.2020.178}, journal={MRS Bulletin}, year={2020}, month={Jun} } @article{hu_obayemi_malatesta_yurkow_adler_soboyejo_2020, title={Luteinizing Hormone-Releasing Hormone (LHRH) Conjugated Magnetite Nanoparticles as MRI Contrast Agents for Breast Cancer Imaging}, volume={10}, url={https://www.mdpi.com/2076-3417/10/15/5175}, DOI={10.3390/app10155175}, abstractNote={Targeted magnetic resonance imaging (MRI) contrast agents offer platforms for the specific detection of many diseases, including cancer. This study explores the applicability of luteinizing hormone-releasing hormone-conjugated PEG-coated magnetite nanoparticles (LHRH-MNPs) to the enhancement of triple negative breast cancer (TNBC) detection. In vitro MRI studies were first performed, showing the consistent darkening effect of both MNPs and LHRH-MNPs in T2-weighted maps. Using a mouse model with an induced subcutaneous tumor, MNPs and LHRH-MNPs were injected into xenograft MDA-MB-231. This was done through intratumoral and intravenous injections, respectively, enabling direction comparisons of the two nanoparticles. Intratumorally injected LHRH-MNPs maintained T2 signals within the breast tumors up to two weeks, revealing long-term tumor enhancement ability, while the signal started to recover towards the contrast of the original tumor before injection in the case of MNPs at 24 h post injection. For intravenous administration, LHRH-MNPs continued to darken breast tumor 24 h following injection, whereas contrast enhancement was not obvious in animals injected with MNPs. These results show the potential of LHRH-MNPs as negative contrast agents for the specific detection of TNBC.}, number={15}, journal={Applied Sciences}, publisher={MDPI AG}, author={Hu, Jingjie and Obayemi, John and Malatesta, Karen and Yurkow, Edward and Adler, Derek and Soboyejo, Winston}, year={2020}, month={Jul}, pages={5175} } @article{albadawi_altun_hu_zhang_panda_kim_khademhosseini_oklu_2020, title={Nanocomposite Hydrogel with Tantalum Microparticles for Rapid Endovascular Hemostasis}, volume={n/a}, url={https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202003327}, DOI={https://doi.org/10.1002/advs.202003327}, abstractNote={Abstract Endovascular embolization to treat vascular hemorrhage involves pushing coil‐shaped metal wires into the artery repeatedly until they are densely packed to slow the blood flow and clot. However, coil embolization is associated with high rebleeding rates, unpredictable economics and, most importantly, they rely on the patient's ability to make a clot. These issues are exacerbated when the patient is anticoagulated or coagulopathic. A novel bioengineered tantalum‐loaded nanocomposite hydrogel for gel embolic material (Ta‐GEM) that can be rapidly delivered using clinical catheters for instant hemostasis regardless of the coagulopathic state is reported. Ta‐GEM formulation is visible by most of the clinically available imaging modalities including ultrasound, computed tomography, magnetic resonance imaging, and fluoroscopy without significant artifact. In addition, Ta‐GEM can be retrieved, allowing temporary vascular occlusion, and it can be used to rescue cases of failed coil embolization. Ta‐GEM occlusion of first‐order arteries such as the renal artery and iliac artery in a swine model is found to be safe and durable; by 28 days, 75% of the injected Ta‐GEM in the arterial lumen is replaced by dense connective tissue. Altogether, this study demonstrates that Ta‐GEM has many advantages over the current technologies and has potential applications in clinical practice.}, number={n/a}, journal={Advanced Science}, author={Albadawi, Hassan and Altun, Izzet and Hu, Jingjie and Zhang, Zefu and Panda, Anshuman and Kim, Han-Jun and Khademhosseini, Ali and Oklu, Rahmi}, year={2020}, month={Nov}, pages={2003327} } @article{ani_obayemi_uzonwanne_danyuo_odusanya_hu_malatesta_soboyejo_2019, title={A shear assay study of single normal/breast cancer cell deformation and detachment from poly-di-methyl-siloxane (PDMS) surfaces}, volume={91}, url={https://doi.org/10.1016/j.jmbbm.2018.11.012}, DOI={10.1016/j.jmbbm.2018.11.012}, abstractNote={This paper presents the results of a combined experimental and analytical/computational study of viscoelastic cell deformation and detachment from poly-di-methyl-siloxane (PDMS) surfaces. Fluid mechanics and fracture mechanics concepts are used to model the detachment of biological cells observed under shear assay conditions. The analytical and computational models are used to compute crack driving forces, which are then related to crack extension during the detachment of normal breast cells and breast cancer cells from PDMS surfaces that are relevant to biomedical implants. The interactions between cells and the extracellular matrix, or the extracellular matrix and the PDMS substrate, are then characterized using force microscopy measurements of the pull-off forces that are used to determine the adhesion energies. Finally, fluorescence microscopy staining of the cytosketelal structures (actin, micro-tubulin and cyto-keratin), transmembrane proteins (vimentin) and the ECM structures (Arginin Glycine Aspartate - RGD) is used to show that the detachment of cells during the shear assay experiments occurs via interfacial cracking between (between the ECM and the cell membranes) with a high incidence of crack bridging by transmembrane vinculin structures that undergo pull-out until they detach from the actin cytoskeletal structure. The implications of the results are discussed for the design of interfaces that are relevant to implantable biomedical devices and normal/cancer tissue.}, journal={Journal of the Mechanical Behavior of Biomedical Materials}, publisher={Elsevier BV}, author={Ani, C.J. and Obayemi, J.D. and Uzonwanne, V.O. and Danyuo, Y. and Odusanya, O.S. and Hu, J. and Malatesta, K. and Soboyejo, W.O.}, year={2019}, month={Mar}, pages={76–90} } @article{hu_albadawi_chong_deipolyi_sheth_khademhosseini_oklu_2019, title={Advances in Biomaterials and Technologies for Vascular Embolization}, url={https://doi.org/10.1002/adma.201901071}, DOI={10.1002/adma.201901071}, abstractNote={Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape‐memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.}, journal={Advanced Materials}, author={Hu, Jingjie and Albadawi, Hassan and Chong, Brian W. and Deipolyi, Amy R. and Sheth, Rahul A. and Khademhosseini, Ali and Oklu, Rahmi}, year={2019}, month={Aug} } @article{compressive deformation and failure of trabecular structures in a turtle shell_2019, url={http://dx.doi.org/10.1016/j.actbio.2019.07.023}, DOI={10.1016/j.actbio.2019.07.023}, abstractNote={Turtle shells comprising of cortical and trabecular bones exhibit intriguing mechanical properties. In this work, compression tests were performed using specimens made from the carapace of Kinixys erosa turtle. A combination of imaging techniques and mechanical testing were employed to examine the responses of hierarchical microstructures of turtle shell under compression. Finite element models produced from microCT-scanned microstructures and analytical foam structure models were then used to elucidate local responses of trabecular bones deformed under compression. The results reveal the contributions from micro-strut bending and stress concentrations to the fractural mechanisms of trabecular bone structures. The porous structures of turtle shells could be an excellent prototype for the bioinspired design of deformation-resistant structures. In this study, a combination of analytical, computational models and experiments is used to study the underlying mechanisms that contribute to the compressive deformation of a Kinixys erosa turtle shell between the nano-, micro- and macro-scales. The proposed work shows that the turtle shell structures can be analyzed as sandwich structures that have the capacity to concentrate deformation and stresses within the trabecular bones, which enables significant energy absorption during compressive deformation. Then, the trends in the deformation characteristics and the strengths of the trabecular bone segments are well predicted by the four-strut model, which captures the effects of variations in strut length, thickness and orientation that are related to microstructural uncertainties of the turtle shells. The above results also suggest that the model may be used to guide the bioinspired design of sandwich porous structures that mimic the properties of the cortical and trabecular bone segments of turtle shells under a range of loading conditions.}, journal={Acta Biomaterialia}, year={2019}, month={Jul} } @article{hu_zhou_obayemi_du_soboyejo_2018, title={An investigation of the viscoelastic properties and the actin cytoskeletal structure of triple negative breast cancer cells}, volume={86}, url={https://doi.org/10.1016/j.jmbbm.2018.05.038}, DOI={10.1016/j.jmbbm.2018.05.038}, abstractNote={An improved understanding of the evolution of cell structure and viscoelasticity with cancer malignancy could enable the development of a new generation of biomarkers and methods for cancer diagnosis. Hence, in this study, we present the viscoelastic properties (moduli and viscosities) and the actin cytoskeletal structures of triple negative breast cancer (TNBC) cells with different metastatic potential. These include: MCF-10A normal breast cells (studied as a control); MDA-MB-468 cells (less metastatic TNBC cells), and MDA-MB-231 cells (highly metastatic TNBC cells). A combination of shear assay and digital imaging correlation (DIC) techniques is used to measure the local viscoelastic properties of live breast cells subjected to constant shear stress. The local moduli and viscosities of the nuclei and cytoplasm are characterized using a generalized Maxwell model, which is used to determine the time-dependent creep responses of cells. The nuclei are shown to be stiffer and more viscous than the cytoplasms of the normal breast cells and TNBC cells. The MCF-10A normal breast cells are found to be twice as stiff as the less metastatic MDA-MB-468 breast cancer cells and over ten times stiffer than the highly metastatic MDA-MB-231 breast cancer cells. Similar trends are also observed in the viscosities of the nuclei and the cytoplasms. The measured differences in cell viscoelastic properties are also associated with significant changes in the cell cytoskeletal structure, which is studied using confocal fluorescence microscopy. This reveals significant differences in the levels of actin expression and organization in TNBC cells as they become highly metastatic. Our results suggest that the shear assay measurements of cell viscoelastic properties may be used as effective biomarkers for TNBC diagnosis and screening.}, journal={Journal of the Mechanical Behavior of Biomedical Materials}, publisher={Elsevier BV}, author={Hu, Jingjie and Zhou, Yuxiao and Obayemi, John D. and Du, Jing and Soboyejo, Winston O.}, year={2018}, month={Oct}, pages={1–13} } @article{hu_obayemi_malatesta_ko?mrlj_soboyejo_2018, title={Enhanced cellular uptake of LHRH-conjugated PEG-coated magnetite nanoparticles for specific targeting of triple negative breast cancer cells}, volume={88}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85043365208&partnerID=MN8TOARS}, DOI={10.1016/j.msec.2018.02.017}, abstractNote={Targeted therapy is an emerging technique in cancer detection and treatment. This paper presents the results of a combined experimental and theoretical study of the specific targeting and entry of luteinizing hormone releasing hormone (LHRH)-conjugated PEG-coated magnetite nanoparticles into triple negative breast cancer (TNBC) cells and normal breast cells. The conjugated nanoparticles structures, cellular uptake of PEG-coated magnetite nanoparticles (MNPs) and LHRH-conjugated PEG-coated magnetite nanoparticles (LHRH-MNPs) into breast cancer cells and normal breast cells were investigated using a combination of transmission electron microscope, optical and confocal fluorescence microscopy techniques. The results show that the presence of LHRH enhances the uptake of LHRH-MNPs into TNBC cells. Nanoparticle entry into breast cancer cells is also studied using a combination of thermodynamics and kinetics models. The trends in the predicted nanoparticle entry times (into TNBC cells) and the size ranges of the engulfed nanoparticles (within the TNBC cells) are shown to be consistent with experimental observations. The implications of the results are then discussed for the specific targeting of TNBCs with LHRH-conjugated PEG-coated magnetite nanoparticles for the early detection and treatment of TNBC.}, journal={Materials Science and Engineering C}, author={Hu, J. and Obayemi, J.D. and Malatesta, K. and Ko?mrlj, A. and Soboyejo, W.O.}, year={2018}, pages={32–45} } @article{hu_youssefian_obayemi_malatesta_rahbar_soboyejo_2018, title={Investigation of adhesive interactions in the specific targeting of Triptorelin-conjugated PEG-coated magnetite nanoparticles to breast cancer cells}, volume={71}, url={https://doi.org/10.1016/j.actbio.2018.02.011}, DOI={10.1016/j.actbio.2018.02.011}, abstractNote={The understanding of adhesive interaction at the nanoscale between functionalized nanoparticles and biological cells is of great importance to develop effective theranostic nanocarriers for targeted cancer therapy. Here, we report a combination of experimental and computational approaches to evaluate the adhesion between Triptorelin (a Luteinizing Hormone-Releasing Hormone (LHRH) agonist)-conjugated poly-(ethylene glycol) (PEG)-coated magnetite nanoparticles (Triptorelin-MNPs) and breast cells. The adhesion forces between Triptorelin-MNPs and normal/cancerous breast cells are obtained using atomic force microscopy. The corresponding work of adhesion is then estimated using Johnson-Kendall-Roberts model. Our results demonstrate that Triptorelin-MNPs have a fourteen-fold greater work of adhesion to breast cancer cells than to normal breast cells. In addition, the work of adhesion between Triptorelin-MNPs and breast cancer cells is found to be three times more than that between unmodified MNPs and breast cancer cells. Hence, the experimental observation indicates that Triptorelin ligands facilitate the specific targeting of breast cancer cells. Furthermore, molecular dynamics simulations are performed to investigate the molecular origins of the adhesive interactions. The simulations reveal that the interactions between molecules (e.g. Triptorelin and PEG) and LHRH receptors are dominated by van der Waals energies, while the interactions of these molecules with cell membrane are dominated by electrostatic interactions. Moreover, both experimental and computational results reveal that PEG serves as an effective coating that enhances adhesive interactions to breast cancer cells that over-express LHRH receptors, while reduces the adhesion to normal breast cells. Our results highlight the potential to develop Triptorelin-MNPs into tumor-specific MRI contrast agents and drug carriers. Systematic investigation of adhesive interactions between functionalized nanoparticles and cancer cells is of great importance in developing effective theranostic nanocarriers for targeted cancer therapy. Herein, we use a combination of atomic force microscopy technique and molecular dynamics simulations approach to explore the adhesive interactions at the nanoscale between Triptorelin-conjugated polyethylene glycol (PEG)-coated magnetite nanoparticles and normal/cancerous breast cells. This study characterizes and quantifies the work of adhesion, as well as adhesion forces, at the nanocarrier/cell interfaces, unravels the molecular origins of adhesive interactions and highlights the effectiveness of PEG coatings and Triptorelin ligands in the specific targeting of breast cancer cells. Our findings expand the fundamental understanding of nanoparticle/cell adhesion and provide guidelines for the design of more rational nanocarriers.}, journal={Acta Biomaterialia}, publisher={Elsevier BV}, author={Hu, Jingjie and Youssefian, Sina and Obayemi, John and Malatesta, Karen and Rahbar, Nima and Soboyejo, Winston}, year={2018}, month={Apr}, pages={363–378} } @article{obayemi_hu_uzonwanne_odusanya_malatesta_anuku_soboyejo_2017, title={Adhesion of ligand-conjugated biosynthesized magnetite nanoparticles to triple negative breast cancer cells}, volume={68}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85013191493&partnerID=MN8TOARS}, DOI={10.1016/j.jmbbm.2017.02.004}, abstractNote={This paper presents the results of an experimental study of the adhesion forces between components of model conjugated magnetite nanoparticle systems for improved selectivity in the specific targeting of triple negative breast cancer. Adhesion forces between chemically synthesized magnetite nanoparticles (CMNPs), biosynthesized magnetite nanoparticles (BMNPs), as well as their conjugated systems and triple negative breast cancer cells (MDA-MB-231) or normal breast cells (MCF 10A) are elucidated at a nanoscale. In all cases, the BMNPs had higher adhesion forces (to breast cancer cells and normal breast cells) than CMNPs. The adhesion of LHRH-conjugated BMNPs or BSA-conjugated BMNPs to cancer cells is shown to be about 6 times to that of normal breast cells. The increase in adhesion forces between luteinizing hormone-releasing hormone, LHRH- or EphA2, a breast specific antibody(BSA)-conjugated BMNPs to breast cancer cells is attributed to van der Waals interactions between the peptides/antibodies from the conjugated nanoparticles and the over-expressed receptors (revealed using immunofluorescence staining) on the surfaces of the breast cancer. The implications of the results are discussed for the selectivity and specificity of breast cancer targeting by ligand-conjugated BMNPs.}, journal={Journal of the Mechanical Behavior of Biomedical Materials}, author={Obayemi, J.D. and Hu, J. and Uzonwanne, V.O. and Odusanya, O.S. and Malatesta, K. and Anuku, N. and Soboyejo, W.O.}, year={2017}, pages={276–286} } @article{dozie-nwachukwu_obayemi_danyuo_etuk-udo_chi_hu_anuku_odusanya_malatesta_soboyejo_2017, title={Biosynthesis of Gold Nanoparticles and Gold/Prodigiosin Nanoparticles with Serratia marcescens Bacteria}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85008204222&partnerID=MN8TOARS}, DOI={10.1007/s12649-016-9734-7}, number={6}, journal={Waste and Biomass Valorization}, author={Dozie-Nwachukwu, S.O. and Obayemi, J.D. and Danyuo, Y.T. and Etuk-Udo, G. and Chi, Y. and Hu, J. and Anuku, N. and Odusanya, O.S. and Malatesta, K. and Soboyejo, W.O.}, year={2017}, pages={2045–2059} } @inproceedings{bedewy_hu_hart_2017, title={Precision control of nanoparticle monolayer assembly: Optimizing rate and crystal quality}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85041200868&partnerID=MN8TOARS}, DOI={10.1109/NANO.2017.8117489}, abstractNote={We study the critical factors that govern the 2D-crystal quality of self-assembled nanoparticles using convective assembly (“blade-casting”) technique. The goal is to improve crystal quality by both maximizing monolayer coverage and optimizing crystal width. We find that crystal quality is enhanced by air plasma treatment on substrate surface, while the monolayer domain size increases with assembly at higher substrate temperature. In addition, we correlate the meniscus shape to array thickness obtained at different deposition stages. Our results provide insights toward scalable production of well-ordered nanoparticle monolayers for applications including biosensors, optically-active surfaces, and nanocomposites.}, booktitle={2017 IEEE 17th International Conference on Nanotechnology, NANO 2017}, author={Bedewy, M. and Hu, J. and Hart, A.J.}, year={2017}, pages={286–289} }