The Effect of Additives on the Behavior of Phase Sensitive In Situ Forming Implants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113738/1/jps24558.pd

Stable Thermally-Modulated Nanodroplet Ultrasound Contrast Agents

Liquid perfluorocarbon-based nanodroplets are stable enough to be used in extravascular imaging, but provide limited contrast enhancement due to their small size, incompressible core, and small acoustic impedance mismatch with biological fluids. Here we show a novel approach to overcoming this limitation by using a heating–cooling cycle, which we will refer to as thermal modulation (TM), to induce echogenicity of otherwise stable but poorly echogenic nanodroplets without triggering a transient phase shift. We apply thermal modulation to high-boiling point tetradecafluorohexane (TDFH) nanodroplets stabilized with a bovine serum albumin (BSA) shell. BSA-TDFH nanodroplets with an average diameter under 300 nanometers showed an 11.9 ± 5.4 mean fold increase in echogenicity on the B-mode and a 13.9 ± 6.9 increase on the nonlinear contrast (NLC) mode after thermal modulation. Once activated, the particles maintained their enhanced echogenicity (p \u3c 0.001) for at least 13 h while retaining their nanoscale size. Our data indicate that thermally modulated nanodroplets can potentially serve as theranostic agents or sensors for various applications of contrast-enhanced ultrasound

Image Guided Biodistribution of Drugs and Drug Delivery

Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drug delivery systems. The application of these new materials and techniques with combined properties of diagnosis and therapy can benefit the development of targeted drug delivery system and modern personalized medicine This special issue provides an up-to-date collection of original research articles and review on the development of novel targeted drug and drug delivery systems combining with non-invasive image guided techniques for chemotherapeutic reagents or DNA delivery

State estimation for coupled reaction-diffusion PDE systems using modulating functions

Many systems with distributed dynamics are described by partial differential equations (PDEs). Coupled reaction-diffusion equations are a particular type of these systems. The measurement of the state over the entire spatial domain is usually required for their control. However, it is often impossible to obtain full state information with physical sensors only. For this problem, observers are developed to estimate the state based on boundary measurements. The method presented applies the so-called modulating function method, relying on an orthonormal function basis representation. Auxiliary systems are generated from the original system by applying modulating functions and formulating annihilation conditions. It is extended by a decoupling matrix step. The calculated kernels are utilized for modulating the input and output signals over a receding time window to obtain the coefficients for the basis expansion for the desired state estimation. The developed algorithm and its real-time functionality are verified via simulation of an example system related to the dynamics of chemical tubular reactors and compared to the conventional backstepping observer. The method achieves a successful state reconstruction of the system while mitigating white noise induced by the sensor. Ultimately, the modulating function approach represents a solution for the distributed state estimation problem without solving a PDE online

Bioresponsive microspheres for on‐demand delivery of anti‐inflammatory cytokines for articular cartilage repair

Despite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine has shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here, we describe the utility of gelatin microspheres that are responsive to proteolytic enzymes typically expressed in arthritic flares, resulting in on‐demand and spatiotemporally controlled release of anti‐inflammatory cytokines for cartilage preservation and repair. These microspheres were designed with a net negative charge to sequester cationic anti‐inflammatory cytokines, and the magnitude of the negative charge potential increased with an increase in crosslinking density. Collagenase‐mediated degradation of the microspheres was dependent on the concentration of the enzyme. Release of anti‐inflammatory cytokines from the loaded microspheres directly correlated with the degradation of the gelatin matrix. Exposure of the IL‐4 and IL‐13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an OA joint can attenuate the stimulation of chondrocytes and the resulting secretion of catabolic factors such as proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically induced drug release. Consequently, bioresponsive microspheres can be an effective tool for cartilage preservation and arthritis treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153665/1/jbma36852_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153665/2/jbma36852.pd

Inflammatory Cells in Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells