Recent years have seen great advances in the development of synthetic self-assembling molecular systems. Designing out-of-equilibrium architectures, however, requires a more subtle control over the thermodynamics and kinetics of reactions. We propose a mechanism for enhancing the thermodynamic drive of DNA strand-displacement reactions whilst barely perturbing forward reaction rates: the introduction of mismatches within the initial duplex. Through a combination of experiment and simulation, we demonstrate that displacement rates are strongly sensitive to mismatch location and can be tuned by rational design. By placing mismatches away from duplex ends, the thermodynamic drive for a stranddisplacement reaction can be varied without significantly affecting the forward reaction rate. This hidden thermodynamic driving motif is ideal for the engineering of non-equilibrium systems that rely on catalytic control and must be robust to leak reactions.

Logic circuits based on DNA strand displacement reactions have been shown to be versatile enough to compute the square root of four-bit numbers. The implementation of these circuits as a set of bulk reactions faces difficulties which include leaky reactions and intrinsically slow, diffusion-limited reaction rates. In this paper, we consider simple examples of these circuits when they are attached to platforms (DNA origamis). As expected, constraining distances between DNA strands leads to faster reaction rates. However, it also induces side-effects that are not detectable in the solution-phase version of this circuitry. Appropriate design of the system, including protection and asymmetry between input and fuel strands, leads to a reproducible behaviour, at least one order of magnitude faster than the one observed under bulk conditions.

Hyaluronan-based hydrogels are among the most promising neural tissue engineering materials because of their biocompatibility and the immunomodulation capabilities of their degradation byproducts. Despite these features, the problems related to their handling and mechanical properties have not yet been solved. In the present work it is proposed to address these drawbacks through the development of nanohybrid materials in which different nanometric phases (carbon nanotubes, mesoporous silica nanoparticles) are embedded in a crosslinked hyaluronan matrix. These nanohybrid matrices were next processed in the shape of cylindrical conduits aimed at promoting and improving neural stem cell differentiation and regeneration in neural tracts. These constructs could be of use specifically for peripheral nerve regeneration.Results of the study show that the inclusion of the different phases improved physico-chemical features of the gel such as its relative electrical permittivity, water intake and elastic modulus, giving hints on how the nanometric phase interacts with hyaluronan in the composite as well as for their potential in combined therapeutic approaches. Regarding the in vitro biological 2 behavior of the hybrid tubular scaffolds, an improved early cell adhesion and survival of Schwann cells in their lumen was found, as compared to conduits made of pure hyaluronan gels. Furthermore, the differentiation and survival of neural precursors was not compromised, despite alleged safety concerns.

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