Growth Factor Functionalized Biomaterial for Drug Delivery and Tissue Regeneration

Elastin-like polypeptides are a class of naturally derived and non-immunogenic biomaterials that are widely used in drug delivery and tissue engineering. Elastin-like polypeptides undergo temperature-mediated inverse phase transitioning, which allows them to be purified in a relatively simple manner from bacterial expression hosts. Being able to genetically encode elastin-like polypeptides allows for the incorporation of bioactive peptides, thereby functionalizing them. Here, we report the synthesis of a biologically active epidermal growth factor–elastin-like polypeptide fusion protein that could aid in wound healing. Epidermal growth factor plays a crucial role in wound healing by inducing cell proliferation and migration. The use of exogenous epidermal growth factor has seen success in the treatment of acute wounds, but has seen relatively minimal success in chronic wounds because the method of delivery does not prevent it from diffusing away from the application site. Our data show that epidermal growth factor–elastin-like polypeptide retained the biological activity of epidermal growth factor and the phase transitioning property of elastin-like polypeptide. Furthermore, the ability of the epidermal growth factor–elastin-like polypeptide to self-assemble near physiological temperatures could allow for the formation of drug depots at the wound site and minimize diffusion, increasing the bioavailability of epidermal growth factor and enhancing tissue regeneration

Growth Factor Functionalized Biomaterial for Drug Delivery and Tissue Regeneration

Elastin-like polypeptides are a class of naturally derived and non-immunogenic biomaterials that are widely used in drug delivery and tissue engineering. Elastin-like polypeptides undergo temperature-mediated inverse phase transitioning, which allows them to be purified in a relatively simple manner from bacterial expression hosts. Being able to genetically encode elastin-like polypeptides allows for the incorporation of bioactive peptides, thereby functionalizing them. Here, we report the synthesis of a biologically active epidermal growth factor–elastin-like polypeptide fusion protein that could aid in wound healing. Epidermal growth factor plays a crucial role in wound healing by inducing cell proliferation and migration. The use of exogenous epidermal growth factor has seen success in the treatment of acute wounds, but has seen relatively minimal success in chronic wounds because the method of delivery does not prevent it from diffusing away from the application site. Our data show that epidermal growth factor–elastin-like polypeptide retained the biological activity of epidermal growth factor and the phase transitioning property of elastin-like polypeptide. Furthermore, the ability of the epidermal growth factor–elastin-like polypeptide to self-assemble near physiological temperatures could allow for the formation of drug depots at the wound site and minimize diffusion, increasing the bioavailability of epidermal growth factor and enhancing tissue regeneration

Microfluidic Device for Examining Directional Sensing in Dendritic Cell Chemotaxis

Dendritic cell chemotaxis is an important process involved in the acquisition of adaptive immunity. Despite several studies, our understanding of this process remains limited. One of the reasons for this is the lack of experimental models that give us real-time information on dendritic cell locomotion. Here, using tools in microfluidics, we have fabricated a microdevice that allows us to monitor dendritic cell migration in a chemokine gradient in real time. We successfully observed the migration of dendritic cells derived from a myeloid leukemia cell line (MUTZ-3) in a soluble chemokine (CCL-19) gradient. Our experiments suggest the utility of microdevices in monitoring dendritic cell chemotaxis in real time and getting important information regarding migration speeds and distances previously not available from conventional chemotaxis assays. This kind of data is useful for building mechanistic mathematical models of dendritic cell chemotaxis that may give us novel insights to the process of dendritic cell chemotaxis

Microfluidic Device for Examining Directional Sensing in Dendritic Cell Chemotaxis

Dendritic cell chemotaxis is an important process involved in the acquisition of adaptive immunity. Despite several studies, our understanding of this process remains limited. One of the reasons for this is the lack of experimental models that give us real-time information on dendritic cell locomotion. Here, using tools in microfluidics, we have fabricated a microdevice that allows us to monitor dendritic cell migration in a chemokine gradient in real time. We successfully observed the migration of dendritic cells derived from a myeloid leukemia cell line (MUTZ-3) in a soluble chemokine (CCL-19) gradient. Our experiments suggest the utility of microdevices in monitoring dendritic cell chemotaxis in real time and getting important information regarding migration speeds and distances previously not available from conventional chemotaxis assays. This kind of data is useful for building mechanistic mathematical models of dendritic cell chemotaxis that may give us novel insights to the process of dendritic cell chemotaxis

JNK phosphorylates β-catenin and regulates adherens junctions

The c-Jun amino-terminal kinase (JNK) is an important player in inflammation, proliferation, and apoptosis. More recently, JNK was found to regulate cell migration by phosphorylating paxillin. Here, we report a novel role of JNK in cell adhesion. Specifically, we provide evidence that JNK binds to E-cadherin/β-catenin complex and phosphorylates β-catenin at serine 37 and threonine 41, the sites also phosphorylated by GSK-3β. Inhibition of JNK kinase activity using dominant-negative constructs reduces phosphorylation of β-catenin and promotes localization of E-cadherin/β-catenin complex to cell-cell contact sites. Conversely, activation of JNK induces β-catenin phosphorylation and disruption of cell contacts, which are prevented by JNK siRNA. We propose that JNK binds to β-catenin and regulates formation of adherens junctions, ultimately controlling cell-to-cell adhesion.—Lee, M.-H., Koria, P., Qu, J., Andreadis, S. T. JNK phosphorylates β-catenin and regulates adherens junctions

Plasmono-magnetic Material for Precise Photothermal Heating

Noble metal nanoparticles have been extensively studied as photo-sensitive agents for photothermal cancer therapy. Precise control over the size and shape of the nanoparticles allowed strong optical absorption and efficient heat generation necessary for destroying a tumor to be achieved. However, one of the fundamental challenges of application of the nanoparticles towards photothermal cancer therapy is low specificity in the targeting tumor tissue in comparison with the healthy tissue and the resulting unfavorable biodistribution of the nanoparticles. Additional levels of control over particle distribution can be achieved by making the particles magnetic and using external magnets to control their accumulation in a tumor. Since the direct synthesis of particles with a magnetic core and a metallic shell limits the options for design and fine-tuning of plasmonic properties, the alternative approaches to the design of such materials have to be investigated. Here we propose and demonstrate a new design of a hybrid plasmono-magnetic material for photothermal heating created by grafting Au nanocages onto a surface of magnetic micro-beads. Next, we confirm its dual functionality in in vitro studies and show that individual hybrid particles can be magnetically controlled with a precision of a few micrometers and precisely destroy individual cells using plasmonic heating

Plasmono-magnetic Material for Precise Photothermal Heating

Noble metal nanoparticles have been extensively studied as photo-sensitive agents for photothermal cancer therapy. Precise control over the size and shape of the nanoparticles allowed strong optical absorption and efficient heat generation necessary for destroying a tumor to be achieved. However, one of the fundamental challenges of application of the nanoparticles towards photothermal cancer therapy is low specificity in the targeting tumor tissue in comparison with the healthy tissue and the resulting unfavorable biodistribution of the nanoparticles. Additional levels of control over particle distribution can be achieved by making the particles magnetic and using external magnets to control their accumulation in a tumor. Since the direct synthesis of particles with a magnetic core and a metallic shell limits the options for design and fine-tuning of plasmonic properties, the alternative approaches to the design of such materials have to be investigated. Here we propose and demonstrate a new design of a hybrid plasmono-magnetic material for photothermal heating created by grafting Au nanocages onto a surface of magnetic micro-beads. Next, we confirm its dual functionality in in vitro studies and show that individual hybrid particles can be magnetically controlled with a precision of a few micrometers and precisely destroy individual cells using plasmonic heating