Stimuli-Responsive Polymer Coatings for the Rapid and Tunable Contact Transfer of Plasmid DNA to Soft Surfaces.

We report the design and characterization of thin polymer-based coatings that promote the contact transfer of DNA to soft surfaces under mild and physiologically relevant conditions. Past studies reveal polymer multilayers fabricated using linear poly(ethylene imine) (LPEI), poly(acrylic acid) (PAA), and plasmid DNA promote contact transfer of DNA to vascular tissue. Here, we demonstrate that changes in the structure of the polyamine building blocks of these materials can have substantial impacts on rates and extents of contact transfer. We used two hydrogel-based substrate models that permit identification and manipulation of parameters that influence contact transfer. We used a planar gel model to characterize films having the structure (cationic polymer/PAA/cationic polymer/plasmid DNA)x fabricated using either LPEI or one of three poly(ß-amino ester)s as polyamine building blocks. The structure of the polyamine influenced subsequent contact transfer of DNA significantly; in general, films fabricated using more hydrophilic polymers promoted transfer more effectively. This planar model also permitted characterization of the stabilities of films transferred onto secondary surfaces, revealing rates of DNA release to be slower than rates of release prior to transfer. We also used a three-dimensional hole-based hydrogel model to evaluate contact transfer of DNA from the surfaces of inflatable catheter balloons used in vascular interventions and selected a rapid-transfer coating for proof-of-concept studies to characterize balloon-mediated contact transfer of DNA to peripheral arterial tissue in swine. Our results reveal robust and largely circumferential transfer of DNA to the luminal walls of peripheral arteries using inflation times as short as 15 to 30 s. The materials and approaches reported here provide new and useful tools for promoting rapid, substrate-mediated contact transfer of plasmid DNA to soft surfaces in vitro and in vivo that could prove useful in a range of fundamental and applied contexts.

Evaluation of changes in shoulder balance and prediction of final shoulder imbalance during growing-rod treatment for early-onset scoliosis.

BACKGROUND: Obtaining and maintaining final shoulder balance after the entire treatment course is essential for early-onset scoliosis (EOS) patients. The relatively small number of growing-rod (GR) graduates who complete final fusion has resulted in an overall paucity of research on the GR treatment of EOS and a lack of research on the shoulder balance of EOS patients during GR treatment. METHODS: Twenty-four consecutive patients who underwent GR treatment until final fusion were included. Radiographic shoulder balance parameters, including the radiographic shoulder height (RSH), clavicle angle (CA), and T1 tilt angle (T1T), before and after each step of the entire treatment were measured. Shoulder balance changes from GR implantation to the last follow-up after final fusion were depicted and analysed. Demographic data, surgical-related factors, and radiographic parameters were analysed to identify risk factors for final shoulder imbalance. The shoulder balance of patients at different time points was further analysed to explore the potential effect of the series of GR treatment steps on shoulder balance. RESULTS: The RSH showed substantial improvement after GR implantation (P = 0.036), during the follow-up period after final fusion (P = 0.021) and throughout the entire treatment (P = 0.011). The trend of change in the CA was similar to that of the RSH, and the T1T improved immediately after GR implantation (P = 0.037). Further analysis indicated that patients with shoulder imbalance before final fusion showed significantly improved shoulder balance after fusion (P = 0.045), and their RSH values at early postfusion and the final follow-up did not show statistically significant differences from those in the prefusion shoulder balance group (P > 0.05). Early postfusion shoulder imbalance (odds ratio (OR): 19.500; 95% confidence interval (CI) = 1.777-213.949; P = 0.015) was identified as an independent risk factor for final shoulder imbalance. CONCLUSIONS: Shoulder balance could be improved by GR implantation but often changes during the multistep lengthening process, and the final result is relatively unpredictable. Final fusion could further adjust the prefusion shoulder imbalance. Focusing on the prefusion shoulder balance of GR graduates and providing patients with early shoulder balance after fusion might be necessary.

Tunable and Selective Degradation of Amine-Reactive Multilayers in Acidic Media.

We report the design of reactive and hydrolytically degradable multilayers by the covalent layer-by-layer assembly of an azlactone-containing polymer, poly(2-vinyl-4,4-dimethylazlactone), with an acid-degradable, acetal-containing, small-molecule diamine linker. This approach yields cross-linked multilayers that contain (i) residual azlactone reactivity that can be used for further functionalization after fabrication and (ii) acid-labile cross-links that can undergo pH-triggered degradation. Thin films and hollow capsules fabricated using this approach were relatively stable in slightly basic media (pH = 7.4) but eroded and degraded gradually in mildly acidic environments (pH = 5). The residual azlactones in these materials could be functionalized by reaction with hydrophilic or hydrophobic amines to tune physicochemical properties, including surface wetting and rates of degradation/erosion. Interestingly, our results reveal that rates of degradation could be tuned over a broad range (from ∼4 h to ∼10 days) simply by post-fabrication modification of the parent reactive material. We further demonstrate the potential of acetal-containing microcapsules to be used for the acid-triggered release of encapsulated cargo. The results of in vitro experiments reveal that microcapsules loaded with fluorescently labeled dextran can be internalized by mammalian cells and that cell uptake and intracellular degradation were also influenced by the types of functional groups installed post-fabrication. The introduction of acid degradability expands the range of stimuli that can be used to trigger the destruction of these reactive materials to include changes in pH relevant to chemical and biological processes. Our results also introduce an approach to tuning degradation profiles that differs from past strategies used to design degradable multilayers. We conclude that this approach provides a new, useful, and modular platform for the design of stimuli-responsive nano/biointerfaces with transient environmental stability.

Covalent Immobilization of Caged Liquid Crystal Microdroplets on Surfaces.

Microscale droplets of thermotropic liquid crystals (LCs) suspended in aqueous media (e.g., LC-in-water emulsions) respond sensitively to the presence of contaminating amphiphiles and, thus, provide promising platforms for the development of new classes of droplet-based environmental sensors. Here, we report polymer-based approaches to the immobilization of LC droplets on surfaces; these approaches introduce several new properties and droplet behaviors and thus also expand the potential utility of LC droplet-based sensors. Our approach exploits the properties of microscale droplets of LCs contained within polymer-based microcapsule cages (so-called "caged" LCs). We demonstrate that caged LCs functionalized with primary amine groups can be immobilized on model surfaces through both weak/reversible ionic interactions and stronger reactive/covalent interactions. We demonstrate using polarized light microscopy that caged LCs that are covalently immobilized on surfaces can undergo rapid and diagnostic changes in shape, rotational mobility, and optical appearance upon the addition of amphiphiles to surrounding aqueous media, including many useful changes in these features that cannot be attained using freely suspended or surface-adsorbed LC droplets. Our results reveal these amphiphile-triggered orientational transitions to be reversible and that arrays of immobilized caged LCs can be used (and reused) to detect both increases and decreases in the concentrations of model contaminants. Finally, we report changes in the shapes and optical appearances of LC droplets that occur when immobilized caged LCs are removed from aqueous environments and dried, and we demonstrate that dried arrays can be stored for months without losing the ability to respond to the presence of analytes upon rehydration. Our results address practical issues associated with the preparation, characterization, storage, and point-of-use application of conventional LC-in-water emulsions and provide a basis for approaches that could enable the development of new "off-the-shelf" LC droplet-based sensing platforms.