Engineered and hybrid human megakaryocytic extracellular vesicles for targeted non-viral cargo delivery to hematopoietic (blood) stem and progenitor cells.

Native and engineered extracellular vesicles generated from human megakaryocytes (huMkEVs) or from the human megakaryocytic cell line CHRF (CHEVs) interact with tropism delivering their cargo to both human and murine hematopoietic stem and progenitor cells (HSPCs). To develop non-viral delivery vectors to HSPCs based on MkEVs, we first confirmed, using NOD-scid IL2Rγnull (NSG™) mice, the targeting potential of the large EVs, enriched in microparticles (huMkMPs), chosen for their large cargo capacity. 24 h post intravenous infusion into NSG mice, huMkEVs induced a nearly 50% increase in murine platelet counts.

Megakaryocyte membrane-wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cells (HSPCs) are desirable targets for gene therapy but are notoriously difficult to target and transfect. Existing viral vector-based delivery methods are not effective in HSPCs due to their cytotoxicity, limited HSPC uptake and lack of target specificity (tropism). Poly(lactic--glycolic acid) (PLGA) nanoparticles (NPs) are attractive, nontoxic carriers that can encapsulate various cargo and enable its controlled release.

Human megakaryocytic microparticles induce de novo platelet biogenesis in a wild-type murine model.

Platelet transfusions are used to treat idiopathic or drug-induced thrombocytopenia. Platelets are an expensive product in limited supply, with limited storage and distribution capabilities because they cannot be frozen. We have demonstrated that, in vitro, human megakaryocytic microparticles (huMkMPs) target human CD34+ hematopoietic stem and progenitor cells (huHSPCs) and induce their Mk differentiation and platelet biogenesis in the absence of thrombopoietin.

Controlled Space Radiation concept for mesh-free semi-analytical technique to model wave fields in complex geometries.

Numerical modelling of the ultrasonic wave propagation is important for Structural Heath Monitoring and System Prognosis problems. In order to develop intelligent and adaptive structures with embedded damage detector and classifier mechanisms, detailed understanding of scattered wave fields due to anomaly in the structure is inevitably required. A detailed understanding of the problem demands a good modelling of the wave propagation in the problem geometry in virtual form.

Locating point of impact in anisotropic fiber reinforced composite plates.

The conventional triangulation technique cannot predict the point of impact in an anisotropic composite plate because the triangulation technique assumes that the wave speed is independent of the direction of propagation which is not the case for anisotropic plates. An alternative method based on the optimization scheme was proposed by Kundu et al. [T.

DPSM modeling for studying interaction between bounded ultrasonic beams and corrugated plates with experimental verification.

Periodically corrugated structures play an important role in the field of vibration control and for designing structures with desired acoustic band gaps. Analytical solutions for corrugated plates are available for well-defined, smooth corrugations, such as sinusoidal corrugations that are not very common in the real world. Often corrugated plates are fabricated by cutting grooves at regular intervals in a flat plate.

Point of impact prediction in isotropic and anisotropic plates from the acoustic emission data.

It is shown in this paper that the conventional triangulation technique is not very reliable for locating the impact point even in isotropic plates when the sensors are placed close to the point of strike for two reasons: First, it is difficult to pinpoint the exact time of arrival of the signal and, second, the Lamb modes in a plate are dispersive. Dispersive signals attenuate differently at various frequencies and propagate with different speeds causing distortions in the received signals, and thus introduce error in the time of flight measurement. The triangulation technique assumes that wave speeds in all directions are the same, which is not true for anisotropic plates.