Quantifying how drug-polymer interaction and volume phase transition modulate the drug release kinetics from core-shell microgels.

This paper presents a simple experimental-informed theory describing the drug release process from a temperature-responsive core-shell microgel. In stark contrast to the commonly employed power-law models, we couple electric, hydrophobic, and steric factors to characterize the impact of drug-polymer pair interaction on the release kinetics. To this end, we also propose a characteristic time, depicting the drug release process as an interplay between kinetics and thermodynamics. In some instances, the negative correlation between the diffusivity and the (thermodynamics) drug-polymer interaction renders the drug release time non-trivial. In conclusion, our theory establishes a mechanistic understanding of the drug release process, exploring the effect of (hydrophobic adhesion) attractive and (steric exclusion) repulsive pair interactions between the drugs and the microgel in the presence of temperature-induced volume phase transition.

How molecular interactions tune the characteristic time of nanocomposite colloidal sensors.

HYPOTHESIS: Mass transport critically controls the performance of colloidal metal-polymer sensors. We hypothesize that molecular-level pair interactions, such as electric, steric, and specific binding effects, govern the mass transport and, in return, the characteristic time of these sensors. THEORY: Here we present a simple theory guided by experimental data to examine the sensing performance of two usually encountered archetypal metal-polymer sensors, namely (1) core-shell and (2) yolk-shell architectures. For this purpose, we use the static reactive density functional theory framework, determining how (i) charge, (ii) size, and (iii) non-covalent binding factors modulate the characteristic time. FINDINGS: We show how an interplay between diffusivity and partitioning governs the sensing time of the sensors, where an anti-correlation cancellation between them renders the time non-trivial. Our study demonstrates that the convoluted substrate-hydrogel shell interaction controls the characteristic time of these colloidal sensors, especially when the sensors are in a collapsed state. Notably, the substrates with a high dipole moment tend to equilibrate greatly, but undesirably, at the shell-solution interface. With this, we encourage the formation of a metastable sorption state.

Reaction-diffusion model to quantify and visualize mass transfer and deactivation within core-shell polymeric microreactors.

HYPOTHESIS: The performance of a polymeric core-shell microreactor depends critically on (i) mass transfer, (ii) catalyzed chemical reaction, and (iii) deactivation within the nonuniform core-shell microstructure environment. As such, these three basic working principles control the active catalytic phase density in the reactor. THEORY: We present a high-fidelity, image-based nonequilibrium computational model to quantify and visualize the mass transport as well as the deactivation process of a core-shell polymeric microreactor. In stark contrast with other published works, our microstructure-based computer simulation can provide a single-particle visualization with a micrometer spatial accuracy. FINDINGS: We show how the interplay of kinetics and thermodynamics controls the product-induced deactivation process. The model predicts and visualizes the non-trivial, spatially resolved active catalyst phase patterns within a core-shell system. Moreover, we also show how the microstructure influences the formation of foulant within a core-shell structure; that is, begins from the core and grows radially onto the shell section. Our results suggest that the deactivation process is highly governed by the porosity/microstructure of the microreactor as well as the affinity of the products towards the solid phase of the reactor.

Modeling the Impact of pH- and Oxygen-Coupled Stimuli on Osmotic Pressure and Electrical Potential Responses of Hemoglobin-Loaded Polyampholyte Hydrogel.

A unique character of (bio) responsive materials is their capability to convert specific environmental biochemical cues into an electromechanical response. Thereby, this paper describes the impact of pH- and oxygen-coupled stimuli on osmotic pressure and electrical potential responses of hemoglobin-loaded polyampholyte hydrogel. Herein, a multiphysics model is developed for elucidating the multiphysical interaction between immobile functional components bounded onto polymeric network chains of the hydrogel and hydrogen ion-oxygen-enriched environmental solution. Two constitutive relationships are incorporated into the model to capture: (1) ionization of fixed charge group as a function of its ionization strength coupled with hydrogen ion concentration and (2) bioactivity of hemoglobin as a function of both its ionization and saturation states. The multiphysics model is verified by comparing with experimental observations in open-literature, capturing the oxygen-induced hemoglobin saturation and the pH-actuated deformation of polyampholyte hydrogel. The numerical finding demonstrates that the pH-activated osmotic pressure response of the present hemoglobin-loaded polymeric system is independent of ambient oxygen O2, whereas its electrical potential response is insensitive of ambient oxygen O2 level at pH neutral conditions. Furthermore, the pH-induced swelling deformation of initially balanced polyampholyte hydrogel changes from a "V-" to a "bowl"-shaped like pattern with increase in fixed acidic and basic group ionization strength, whereas the initially unbalanced polyampholyte hydrogel achieves a collapse state at environmental pH coinciding with acid-base dissociation constant of dominant immobile charge group, if the initial dominant immobile charge group density is twice that of its counter one.

Development of a multiphysics model to characterize the responsive behavior of urea-sensitive hydrogel as biosensor.

A remarkable feature of biomaterials is their ability to deform in response to certain external bio-stimuli. Here, a novel biochemo-electro-mechanical model is developed for the numerical characterization of the urea-sensitive hydrogel in response to the external stimulus of urea. The urea sensitivity of the hydrogel is usually characterized by the states of ionization and denaturation of the immobilized urease, as such the model includes the effect of the fixed charge groups and temperature coupled with pH on the activity of the urease. Therefore, a novel rate of reaction equation is proposed to characterize the hydrolysis of urea that accounts for both the ionization and denaturation states of the urease subject to the environmental conditions. After examination with the published experimental data, it is thus confirmed that the model can characterize well the responsive behavior of the urea-sensitive hydrogel subject to the urea stimulus, including the distribution patterns of the electrical potential and pH of the hydrogel. The results point to an innovative means for generating electrical power via the enzyme-induced pH and electrical potential gradients, when the hydrogel comes in contact with the urea-rich solution, such as human urine.

Tissue expanders in the lower face and anterior neck in pediatric burn patients: limitations and pitfalls.

Radovan's 1982 landmark work on the clinical use of tissue expanders was felt to be a panacea for multiple reconstructive problems. We have used and probably overused tissue expanders for reconstruction of many complicated pediatric facial burn problems. This has enlightened us to some of the limitations of their use, and we have, therefore, reassessed our indications for their use. From 1984 through 1990, 52 tissue expanders were used in 37 pediatric patients for face and anterior neck burn scar resurfacing. This experience, combined with the unique problems encountered with face and neck tissue expansion, provided the groundwork for operative guidelines. The long-term effects of gravity, growth, and scarring on facial features adjacent to expanded skin led to the following principles. (1) Caution should be used in advancing expanded neck skin beyond the border of the mandible. The risk of scar widening or possible lip or eyelid ectropion needs to be considered when planning these flaps. Extreme overexpansion is necessary to advance unburned neck flaps over the mandibular border to avoid these problems. (2) After advancement or rotational flaps neck flaps to the face, vertically directed suture lines in the neck may need redirection to prevent linear contracture. This correction may be performed during the primary operation or during revisions. (3) Expanded cheek or neck skin should preferably replace burned areas, but at the same time, not violate unburned facial aesthetic units. (4) To counteract the affects of gravity, expanded cheek skin in conjunction with expanded neck skin, if unburned, may be the best choice for face or mandibular border scar replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of thyrotropin-releasing hormone receptors and responses by L-triiodothyronine in dispersed rat pituitary cell cultures.

The effects of physiological concentrations of L-T3 (T3) were examined in dispersed cell cultures of pituitaries obtained from 10- to 12-day-old rats. T3 inhibited TSH secretion by 50% and blunted the TSH response to TRH. The PRL response to TRH was also inhibited by T3, and GH secretion was increased 2-fold. These responses were half-maximal at 0.1 nM added T3 in medium supplemented with 10% hypothyroid calf serum, corresponding to a free T3 concentration of 5 pM. In the presence or absence of added T3, TRH effects were half-maximal at 0.5-3 nM, and T3 suppression was not overcome by high concentrations of TRH (up to 1 microM). Maximal inhibition of TSH responses to TRH occurred when cultures were preincubated with thyroid hormone for 24 h; a significant effect was observed after 8 h. The specific binding of [3H]TRH to dispersed rat pituitary cells was decreased 55-70% by T3 in a dose-dependent manner. Inhibition of TSH secretion by T3 was reversible within 24 h, and the fraction of thyrotrophs in the cultures (0.22) was not altered by T3 over the course of the experiments. The results demonstrate that physiological concentrations of T3 regulate TSH and PRL responses to TRH and control TRH receptor levels by a direct action on normal rat pituitary cells.