Applications of focused ultrasound-mediated blood-brain barrier opening.

The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts.

Structurally abnormal collagen fibrils in abdominal aortic aneurysm resist platelet adhesion.

Background: Platelet adhesion to the subendothelial collagen fibrils is one of the first steps in hemostasis. Understanding how structural perturbations in the collagen fibril affect platelet adhesion can provide novel insights into disruption of hemostasis in various diseases. We have recently identified the presence of abnormal collagen fibrils with compromised D-periodic banding in the extracellular matrix remodeling present in abdominal aortic aneurysms (AAA).

Ultrasound-targeted nucleic acid delivery for solid tumor therapy.

Depending upon multiple factors, malignant solid tumors are conventionally treated by some combination of surgical resection, radiation, chemotherapy, and immunotherapy. Despite decades of research, therapeutic responses remain poor for many cancer indications. Further, many current therapies in our armamentarium are either invasive or accompanied by toxic side effects.

Collagen fibril abnormalities in human and mice abdominal aortic aneurysm.

Vascular diseases like abdominal aortic aneurysms (AAA) are characterized by a drastic remodeling of the vessel wall, accompanied with changes in the elastin and collagen content. At the macromolecular level, the elastin fibers in AAA have been reported to undergo significant structural alterations. While the undulations (waviness) of the collagen fibers is also reduced in AAA, very little is understood about changes in the collagen fibril at the sub-fiber level in AAA as well as in other vascular pathologies.

Independent control of matrix adhesiveness and stiffness within a 3D self-assembling peptide hydrogel.

Unlabelled: A cell's insoluble microenvironment has increasingly been shown to exert influence on its function. In particular, matrix stiffness and adhesiveness strongly impact behaviors such as cell spreading and differentiation, but materials that allow for independent control of these parameters within a fibrous, stromal-like microenvironment are very limited. In the current work, we devise a self-assembling peptide (SAP) system that facilitates user-friendly control of matrix stiffness and RGD (Arg-Gly-Asp) concentration within a hydrogel possessing a microarchitecture similar to stromal extracellular matrix.