Targeting CD14 on blood derived cells improves intracortical microelectrode performance.

Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity. Additionally, intracortical microelectrodes have the ability to return function to individuals with paralysis as part of a brain computer interface. Unfortunately, the neural signals recorded by these electrodes degrade over time.

Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance.

Objective: Neuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration.

The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.

Resident microglia and blood-borne macrophages have both been implicated to play a dominant role in mediating the neuroinflammatory response affecting implanted intracortical microelectrodes. However, the distinction between each cell type has not been demonstrated due to a lack of discriminating cellular markers. Understanding the subtle differences of each cell population in mediating neuroinflammation can aid in determining the appropriate therapeutic approaches to improve microelectrode performance.

The Effect of Residual Endotoxin Contamination on the Neuroinflammatory Response to Sterilized Intracortical Microelectrodes.

A major limitation to the use of microelectrode technologies in both research and clinical applications is our inability to consistently record high quality neural signals. There is increasing evidence that recording instability is linked, in part, to neuroinflammation. A number of factors including extravasated blood products and macrophage released soluble factors are believed to mediate neuroinflammation and the resulting recording instability.

A comparison of neuroinflammation to implanted microelectrodes in rat and mouse models.

Rat models have emerged as a common tool to study neuroinflammation to intracortical microelectrodes. While a number of studies have attempted to understand the factors resulting in neuroinflammation using rat models, a complete understanding of key mechanistic pathways remains elusive. Transgenic mouse models, however, could facilitate a deeper understanding of mechanistic pathways due to an ease of genetic alteration.

In vitro and in vivo hemostatic capabilities of a functionally integrated platelet-mimetic liposomal nanoconstruct.

There is significant clinical interest in synthetic platelet substitutes that can mimic platelet's hemostastic functionalities while allowing scale-up, minimal biological contamination, and long shelf-life. To this end, mimicking active platelet's hemostatically relevant matrix-adhesion properties and aggregation properties independently and then integrating them via heteromultivalent ligand decoration on a single synthetic particle can lead to an efficient platelet substitute design. We have recently reported on the feasibility of this approach in vitro, using liposomes as model particles.

An organotypic spinal cord slice culture model to quantify neurodegeneration.

Activated microglia cells have been implicated in the neurodegenerative process of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis; however, the precise roles of microglia in disease progression are unclear. Despite these diseases having been described for more than a century, current FDA approved therapeutics are symptomatic in nature with little evidence to supporting a neuroprotective effect. Furthermore, identifying novel therapeutics remains challenging due to undetermined etiology, a variable disease course, and the paucity of validated targets.

Mimicking adhesive functionalities of blood platelets using ligand-decorated liposomes.

Platelet transfusion is used for treating a variety of bleeding complications. Natural platelet-based transfusion products have very short storage life (3-7 days) and high risks of biological contamination and side effects. Consequently, there is significant clinical interest in synthetic platelet-mimetic constructs that can promote hemostasis, while allowing convenient large-scale production, easy portability, long storage life, and minimal biological risks.

Peptide-decorated liposomes promote arrest and aggregation of activated platelets under flow on vascular injury relevant protein surfaces in vitro.

Platelet-mimetic synthetic hemostats are highly attractive in transfusion medicine. To this end, past research reports have described particles that either amplify platelet aggregation or mimic platelet adhesion. However, a construct design that effectively combines both functionalities has not been reported.

Heteromultivalent liposomal nanoconstructs for enhanced targeting and shear-stable binding to active platelets for site-selective vascular drug delivery.

Activated platelets play multiple roles in vascular diseases. Hence, a delivery vehicle that can specifically target activated platelets and stay retained under a hemodynamic environment can potentially enhance the efficacy of vehicle-encapsulated vascular drug by protecting it from rapid plasma deactivation, reducing its systemic non-specific side-effects, and increasing its therapeutic index at disease sites undergoing platelet hyperactivity. We rationalized that liposomal nanoconstructs surface-modified with two kinds of peptide that simultaneously bind integrin α(IIb)β(3) and P-selectin on activated platelets can provide synergistic mechanisms for enhanced selectivity to vascular disease sites.