Multifunctional platform based on electrospun nanofibers and plasmonic hydrogel. A smart nanostructured pillow for near-infrared light-driven biomedical applications

Multifunctional nanomaterials with the ability to respond to near-infrared (NIR) light stimulation are vital for the development of highly efficient biomedical nanoplatforms with a polytherapeutic approach. Inspired by the mesoglea structure of jellyfish bells, a biomimetic multifunctional nanostructured pillow with fast photothermal responsiveness for NIR light-controlled on-demand drug delivery is developed. We fabricate a nanoplatform with several hierarchical levels designed to generate a series of controlled, rapid, and reversible cascade-like structural changes upon NIR light irradiation. The mechanical contraction of the nanostructured platform, resulting from the increase of temperature to 42 °C due to plasmonic hydrogel-light interaction, causes a rapid expulsion of water from the inner structure, passing through an electrospun membrane anchored onto the hydrogel core. The mutual effects of the rise in temperature and water flow stimulate the release of molecules from the nanofibers. To expand the potential applications of the biomimetic platform, the photothermal responsiveness to reach the typical temperature level for performing photothermal therapy (PTT) is designed. The on-demand drug model penetration into pig tissue demonstrates the efficiency of the nanostructured platform in the rapid and controlled release of molecules, while the high biocompatibility confirms the pillow potential for biomedical applications based on the NIR light-driven multitherapy strategy

Sp6 and Sp8 transcription factors control AER formation and dorsal-ventral patterning in limb development

The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6-/-;Sp8+/-) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/βcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning

An example of U-shaped hydrogel nanofilament in the oscillatory flow, <i>d</i> = 181 nm, <i>L</i> = 32 μm, <i>V</i>_<i>max</i> = 282 μm/s, <i>U</i>_<i>r</i> <i>=</i> 10⁻³.

<p>(a)–lateral migration path of the nanofilament into the channel axis, center of mass position at each zero-crossing of the flow oscillation (n * π, n = 1,2,3.); (b)–relative longitudinal slip velocity <i>U</i>_<i>s</i> of the filament observed for each maxima of the oscillating flow (n * π/2, n = 1,3,5.). Remarkable out of phase pattern due to the filament deformations.</p

Selected characteristics of hydrogel nanofilaments analyzed in the present experiment compared with the bead-spring WLC model [18–20] and the experiment with polymer fibers [18].

<p><i>Sp</i>, <i>Pe</i>, <i>K</i>, <i>A</i>, <i>U</i>_<i>r</i>, <i>U</i>_<i>s</i> of hydrogel nanofilaments are reported as range of values and as mean ± standard deviation.</p

Lateral migration of electrospun hydrogel nanofilaments in an oscillatory flow

<div><p>The recent progress in bioengineering has created great interest in the dynamics and manipulation of long, deformable macromolecules interacting with fluid flow. We report experimental data on the cross-flow migration, bending, and buckling of extremely deformable hydrogel nanofilaments conveyed by an oscillatory flow into a microchannel. The changes in migration velocity and filament orientation are related to the flow velocity and the filament’s initial position, deformation, and length. The observed migration dynamics of hydrogel filaments qualitatively confirms the validity of the previously developed worm-like bead-chain hydrodynamic model. The experimental data collected may help to verify the role of hydrodynamic interactions in molecular simulations of long molecular chains dynamics.</p></div

Statistics of cross-stream migration.

<p>(a)—distribution of hydrogel nanofilaments across the microchannel between centerline (0) and wall (1) at initial (<i>grey bars</i>) and final (<i>dashed contour lines</i>) oscillatory cycle; (b)—relative filament slip velocity <i>Us</i> for the three groups; (c)—relative change of the inclination angle for each group of nanofilaments: final orientation (<i>dashed-patterned bars</i>) normalized to the initial orientation (<i>grey bars</i>).</p

Lateral migration for hydrogel nanofilaments.

<p>(a)—toward the channel center (<i>d = 105 nm</i>, <i>L = 41</i> μ<i>m</i>, <i>V</i>_<i>max</i> <i>= 250</i> μ<i>m/s</i>, <i>relative migration velocity U</i>_<i>r</i> <i>= 0</i>.<i>85 10</i>^<i>−3</i>; (b)—toward the wall (<i>d = 134 nm</i>, <i>L = 54</i> μ<i>m</i>, <i>V</i>_<i>max</i> <i>= 132</i> μ<i>m/s</i>, <i>U</i>_<i>r</i> <i>= 0</i>.<i>6 10</i>^<i>−3</i>.</p

Flow induced changes in nanofilament shape observed after 9–10 oscillatory cycles.

<p>Variation of degree of buckling for bent (a, b), U-shaped stretched (c, d) and U-shaped buckled (e, f) nanofilaments recorded at each forward (<i>left column</i>) and reversed (<i>right column</i>) oscillatory cycle. Solid lines indicate the data trend. (g)–changes in the end-to-end contour length distribution for the three groups of nanofilaments, at the initial oscillatory cycle (<i>grey bars</i>) and after the final cycle (<i>dashed-pattern bars</i>).</p