The effective and sustained delivery of DNA and siRNAs locally would increase the applicability of gene therapy in tissue regeneration and cancer therapy. One promising approach is to use hydrogel scaffolds to encapsulate and deliver nucleotides in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated and active gene delivery nanoparticles into the hydrogels due to the severe nanoparticle aggregation during the loading process. Here, we present a process to load concentrated and un-aggregated non-viral gene delivery nanoparticles, using DNA/polyethylene imine (PEI) polyplexes as an example, into neutral polyethylene glycol (PEG), negatively charged hyaluronic acid (HA) and protein fibrin hydrogels crosslinked through various chemistries. The encapsulated polyplexes are highly active both in vitro and in vivo. We believe this process will significantly advance the applications of hydrogel scaffold mediated non-viral gene delivery in tissue regeneration and cancer therapy.
Figure 1: A soft sponge is twisted. It fractures and collides with itself. The failure and contact phenomena are resolved automatically by the MPM approach.
AbstractWe present a new Material Point Method (MPM) for simulating viscoelastic fluids, foams and sponges. We design our discretization from the upper convected derivative terms in the evolution of the left Cauchy-Green elastic strain tensor. We combine this with an Oldroyd-B model for plastic flow in a complex viscoelastic fluid. While the Oldroyd-B model is traditionally used for viscoelastic fluids, we show that its interpretation as a plastic flow naturally allows us to simulate a wide range of complex material behaviors. In order to do this, we provide a modification to the traditional Oldroyd-B model that guarantees volume preserving plastic flows. Our plasticity model is remarkably simple (foregoing the need for the singular value decomposition (SVD) of stresses or strains). Lastly, we show that implicit time stepping can be achieved in a manner similar to [Stomakhin et al. 2013] and that this allows for high resolution simulations at practical simulation times.
Laser confocal microscopy is used to non-invasively investigate the steady and unsteady evolution of viscous microdroplets on solid substrates. Three characteristic dynamical regimes of spreading drops (viscous-capillary, viscous-inertia-capillary, and inertia-capillary) are studied using this non-invasive optical technique. It is shown that the dynamics of each regime depend on the Ohnesorge number, Oh = v/(zR|) 1 2 , and on the relative magnitudes of the droplet height, radius, compared with the capillary length, l cap = |/zg. The power-law relationships between the extent of spreading and elapsed time that are extracted from the experiments are in excellent agreement with available analytical results. We also study the onset and evolution of surface instabilities of the slightly volatile liquid films as they spread across the thermally-conductive surfaces. When the fluid droplet is a volatile silicone oil and the surface is a smooth silicon wafer, an evaporatively-driven thermocapillary instability leads to onset of a time-dependent free surface motion. Below a certain critical thickness ( 20 mm), waves can be observed on the free surface of the film, and the confocal technique is used to measure the amplitude, the frequency, and non-linear evolution of these waves. We interpret these waves in terms of evaporatively-driven Marangoni instabilities induced by surface tension gradients close to the moving contact line. Experiments show that the amplitude and the critical onset thickness of the disturbances vary with the viscosity and the volatility of the liquid, and also with the surface roughness and thermal diffusivity of the substrate. The critical onset conditions for this evaporatively driven instability can be characterized by a dimensionless interfacial thermal resistance, R, which has to be larger than a critical value at the onset of instability. We also demonstrate that this evaporatively-driven Marangoni instability can be eliminated by reducing the volatility of the liquid or the thermal diffusivity of the substrate.
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