Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause death worldwide. Here, we describe biomimetic strategy that uses high shear stress caused by vascular narrowing as targeting mechanism--in the same way platelets do--to deliver drugs obstructed vessels. Microscale aggregates nanoparticles were fabricated break up into nanoscale components when exposed abnormally fluid stress. When coated with tissue plasminogen activator and administered intravenously in...

Cyclic mechanical strain produced by pulsatile blood flow regulates the orientation of endothelial cells lining vessels and influences critical processes such as angiogenesis. Mechanical stimulation stretch-activated calcium channels is known to mediate this reorientation response; however, molecular basis remains unknown. Here, we show that cyclically stretching capillary adherent flexible extracellular matrix substrates activates mechanosensitive TRPV4 (transient receptor potential...

Hyaluronan (HA) hydrogels resist attachment and spreading of fibroblasts most other mammalian cell types. A thiol-modified HA (3,3'-dithiobis(propanoic dihydrazide) [HA-DTPH]) was modified with peptides containing the Arg-Gly-Asp (RGD) sequence then crosslinked polyethylene glycol (PEG) diacrylate (PEGDA) to create a biomaterial that supported attachment, spreading, proliferation. The were evaluated in vitro vivo three assay systems. First, behavior human murine on surface evaluated....

Tumor blood vessels exhibit abnormal structure and function that cause disturbed flow high interstitial pressure, which impair delivery of anti-cancer agents. Past efforts to normalize the tumor vasculature have focused on inhibition soluble angiogenic factors, such as VEGF; however, capillary endothelial (CE) cell growth differentiation during angiogenesis are also influenced by mechanical forces conveyed extracellular matrix (ECM). Here, we explored possibility CE cells form because they...

Fibronectin (FN) facilitates dermal fibroblast migration during normal wound healing. Proteolytic degradation of FN in chronic wounds hampers Previously, three functional domains (FNfd) have been shown to be sufficient for optimal adult human migration. Here we report the development an acellular hydrogel matrix comprised FNfds coupled a hyaluronan (HA) backbone stimulate repair. Employing Michael-type addition, cysteine- tagged were first homobifunctional PEG derivative. Thereafter, these...

A cancer nanotherapeutic has been developed that targets the extracellular matrix (ECM)-modifying enzyme lysyl oxidase (LOX) and alters ECM structure. Poly(d,l-lactide-co-glycolide) nanoparticles (∼220 nm) coated with a LOX inhibitory antibody bind to suppress mammary cell growth invasion in vitro as well tumor expansion vivo, greater efficiency than soluble anti-LOX antibody. This nanomaterials approach opens new path for treating higher efficacy decreased side effects.

This report investigates the rheological properties of cross-linked, thiol-functionalized HA (HA−DTPH) hydrogels prepared by varying concentration and molecular weight (MW) cross-linker, poly(ethylene glycol) diacrylate (PEGDA). Hydrogels were subsequently cured for either short-term (hours) or long-term (days) subjected to oscillatory shear rheometry (OSR). OSR allows evaluation comparison storage moduli (G'), an index total number effective cross-links formed in hydrogels. While time sweep...

Abstract Summary: A facile fabrication of a cross‐linked hyaluronic acid (HA) hydrogel nanofibers by reactive electrospinning method is described. thiolated HA derivative, 3,3′‐dithiobis(propanoic dihydrazide)‐modified (HA‐DTPH), and poly(ethylene glycol) diacrylate (PEGDA) are selected as the cross‐linking system. The reaction occurs simultaneously during process using dual‐syringe mixing technique. Poly(ethylene oxide) (PEO) added into spinning solution viscosity modifier to facilitate...

Abstract We used the electrospinning technique to produce fibrous scaffolds of poly(methyl methacrylate) (PMMA). Using a rotating drum, we aligned fibers and formed multilayered structures where both fiber spacing pore size could be varied. then plated adult human dermal fibroblasts studied effect diameter orientation on cell conformation, integrin receptor expression, proliferation, migration. found that critical minimum existed, D 0 = 0.97 μm for occur. For < , no big difference in...

Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than African-Americans. Here we found melanocytes from humans albino mice secrete high levels fibromodulin (FMOD), which determined to be a potent angiogenic factor. FMOD treatment stimulated...

Endothelial activation is a hallmark of the high-glucose (HG)-induced retinal inflammation associated with diabetic retinopathy (DR). However, precisely how HG induces endothelial not fully understood. We hypothesized that HG-induced up-regulation lysyl oxidase (LOX), collagen-cross-linking enzyme, in capillary cells (ECs) enhances subendothelial basement membrane (BM) stiffness, which, turn, promotes EC activation. Diabetic C57BL/6 mice exhibiting 70 and 50% increase intercellular adhesion...

Purpose: Age-related macular degeneration (AMD) commonly causes blindness in the elderly. Yet, it is untreatable large fraction of all AMD patients that develop early dry form. Dry marked by deposition membrane attack complex (MAC) on choriocapillaris (CC), which implicated CC and subsequent atrophy overlying retinal pigment epithelium. Since MAC also found young eyes, here we investigated whether how aging increases choroidal endothelial susceptibility to injury. Methods: Monkey...

Endothelial cell (EC) activation is a crucial determinant of retinal vascular inflammation associated with diabetic retinopathy (DR), major microvascular complication diabetes. We previously showed that, similar to abnormal biochemical factors, aberrant mechanical cues in the form lysyl oxidase (LOX)-dependent subendothelial matrix stiffening also contribute significantly EC Yet, how LOX itself regulated and precisely it mechanically controls diabetes poorly understood. Here, we show that...

Here we report a proof-of-concept for development of pancreatic islet-targeting nanoparticles immunomodulatory therapy autoimmune type 1 diabetes. Modified with unique islet-homing peptide, these polymeric nanomaterials exhibit 3-fold greater binding to islet endothelial cells and 200-fold anti-inflammatory effect through targeted cell delivery an immunosuppressant drug. Our findings also underscore the need carefully tailor drug loading nanoparticle dosage achieve maximal vascular targeting...

Journal Article Matrix stiffness exerts biphasic control over monocyte–endothelial adhesion via Rho-mediated ICAM-1 clustering Get access Harry A. Scott, Scott Department of Bioengineering, University California Riverside, 900 Avenue, MSE 207, CA 92521, USA Search for other works by this author on: Oxford Academic Google Scholar Boi Quach, Quach Xiao Yang, Yang Soroush Ardekani, Ardekani Andrea P. Cabrera, Cabrera Randall Wilson, Wilson Division Biomedical Sciences, Ilhem Messaoudi-Powers,...

Age-related macular degeneration (AMD) is the leading cause of blindness in aging population. Yet no therapies exist for ~85% all AMD patients who have dry form that marked by retinal pigmented epithelium (RPE) and underlying choroidal vasculature. As vessels are crucial RPE development maintenance, understanding how they degenerate may lead to effective AMD. One likely causative factor vascular loss cytolytic membrane attack complex (MAC) complement pathway abundant on humans with early To...

Inflammation plays an important role in the pathogenesis of diabetic retinopathy (DR). We have previously reported increased monocyte (Mono) trafficking into retinas animals. In this study, we examined effect activated Monos on retinal endothelial cells (ECs). The U937 Mφ-conditioned medium (CM) significantly decreased transendothelial resistance EC monolayers as measured by electric cell-substrate impedance sensing (P = 0.007). CM was fractioned, and effective fraction (30–100 kDa) analyzed...

Vascular inflammation is known to cause degeneration of retinal capillaries in early diabetic retinopathy (DR), a major microvascular complication diabetes. Past studies investigating these diabetes-induced vascular abnormalities have focused primarily on the role molecular or biochemical cues. Here we show that and diabetes are also mechanically regulated by increase stiffness caused overexpression collagen-cross-linking enzyme lysyl oxidase (LOX). Treatment mice with LOX inhibitor...