Injury-on-a-chip for modelling microvascular trauma-induced coagulation.

Blood coagulation is a highly regulated injury response that features polymerization of fibrin fibers to prevent the passage of blood from a damaged vascular endothelium. A growing body of research seeks to monitor coagulation in microfluidic systems but fails to capture coagulation as a response to disruption of the vascular endothelium. Here we present a device that allows compression injury of a defined segment of a microfluidic vascular endothelium and the assessment of coagulation at the injury site.

Simple Design for Membrane-Free Microphysiological Systems to Model the Blood-Tissue Barriers.

Microphysiological systems (MPS) incorporate physiologically relevant microanatomy, mechanics, and cells to mimic tissue function. Reproducible and standardized models of tissue barriers, such as the blood-tissue interface (BTI), are critical for next-generation MPS applications in research and industry. Many models of the BTI are limited by the need for semipermeable membranes, use of homogenous cell populations, or 2D culture.

Molecular engineering of cyclic azobenzene-peptide hybrid ligands for the purification of human blood Factor VIII via photo-affinity chromatography.

The use of benign stimuli to control the binding and release of labile biologics for their isolation from complex feedstocks is a key goal of modern biopharmaceutical technology. This study introduces cyclic azobenzene-peptide (CAP) hybrid ligands for the rapid and discrete photo-responsive capture and release of blood coagulation Factor VIII (FVIII). A predictive method - based on amino acid sequence and molecular architecture of CAPs - was developed to correlate the conformation of CAP photo-isomers to FVIII binding and release.

Hypoxia Primes Human ISCs for Interleukin-Dependent Rescue of Stem Cell Activity.

Background And Aims: Hypoxia in the intestinal epithelium can be caused by acute ischemic events or chronic inflammation in which immune cell infiltration produces inflammatory hypoxia starving the mucosa of oxygen. The epithelium has the capacity to regenerate after some ischemic and inflammatory conditions suggesting that intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of hypoxia on human ISC (hISC) function has not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs from healthy donors and test the hypothesis that prolonged hypoxia modulates how hISCs respond to inflammation-associated interleukins (ILs).

Rheological characterization of poly-dimethyl siloxane formulations with tunable viscoelastic properties.

Studies from the past two decades have demonstrated convincingly that cells are able to sense the mechanical properties of their surroundings. Cells make major decisions in response to this mechanosensation, including decisions regarding cell migration, proliferation, survival, and differentiation. The vast majority of these studies have focused on the cellular mechanoresponse to changing substrate stiffness (or elastic modulus) and have been conducted on purely elastic substrates.

Synthetic platelet microgels containing fibrin knob B mimetic motifs enhance clotting responses.

Native platelets are crucial players in wound healing. Key to their role is the ability of their surface receptor GPIIb/IIIa to bind fibrin at injury sites, thereby promoting clotting. When platelet activity is impaired as a result of traumatic injury or certain diseases, uncontrolled bleeding can result.

Fibrin-modulating nanogels for treatment of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a pathological coagulopathy associated with infection that increases mortality. In DIC, excessive thrombin generation causes symptoms from formation of microthrombi to multiorgan failure; bleeding risks can also be a concern because of clotting factor consumption. Different clinical events lead to DIC, including sepsis, trauma, and shock.

Microphysiological systems for the modeling of wound healing and evaluation of pro-healing therapies.

Wound healing is a multivariate process involving the coordinated response of numerous proteins and cell types. Accordingly, biomedical research has seen an increased adoption of the use of in vitro wound healing assays with complexity beyond that offered by traditional well-plate constructs. These microphysiological systems (MPS) seek to recapitulate one or more physiological features of the in vivo microenvironment, while retaining the analytical capacity of more reductionist assays.