Formation of asymmetric, rigid scar tissue known as surgical adhesions is caused by traumatic disruption of mesothelial-lined surfaces in surgery. A widely adopted prophylactic barrier material (Seprafilm) for the treatment of intra-abdominal adhesions is applied operatively as a pre-dried hydrogel sheet but has reduced translational efficacy due its brittle mechanical properties. Topically administered peritoneal dialysate (Icodextrin) and anti-inflammatory drugs have failed to prevent adhesions due to an uncontrolled release profile. Hence, inclusion of a targeted therapeutic into a solid barrier host matrix with improved mechanical properties could provide dual utility in adhesion prevention and as a surgical sealant. Spray deposition of poly(lactide-co-caprolactone) (PLCL) polymer fibers through solution blow spinning has yielded a tissue-adherent barrier material with previously reported adhesion prevention efficacy due to a surface erosion mechanism that inhibits deposition of inflamed tissue. However, such an approach uniquely presents an avenue for controlled therapeutic release through mechanisms of diffusion and degradation. Such a rate is kinetically tuned via facile blending of “high” molecular weight (HMW) and “low” molecular weight (LMW) PLCL with slow and fast biodegradation rates, respectively. Here, we explore viscoelastic blends of HMW PLCL (70% w/v) and LMW PLCL (30% w/v) as a host matrix for anti-inflammatory drug delivery. In this work, COG133, an apolipoprotein E (ApoE) mimetic peptide with potent anti-inflammatory properties was selected and tested. In vitro studies with PLCL blends presented low (∼30%) and high (∼80%) percent release profiles over a 14-day period based on the nominal molecular weight of the HMW PLCL component. Two independent mouse models of cecal ligation and cecal anastomosis significantly reduced adhesion severity versus Seprafilm, COG133 liquid suspension, and no treatment control. The synergy of physical and chemical methods in a barrier material with proven preclinical studies highlights the value of COG133-loaded PLCL fiber mats in effectively dampening the formation of severe abdominal adhesions.

Abstract Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue‐conforming and tissue‐adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic‐co‐glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide‐co‐caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy‐to‐apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through the design of PLCL blends comprised of highly adhesive “low”‐molecular weight (LMW) constituents in a mechanically robust “high”‐molecular weight (HMW) matrix. In vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti‐fibrotic yet tissue‐adhesive polymer sealant with a 14‐day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14‐day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm‐treated controls.

Pressure-sensitive adhesives typically used for bandages are nonbiodegradable, inhibiting healing, and may cause an allergic reaction. Here, we investigated the effect of biodegradable copolymers with promising thermomechanical properties on wound healing for their eventual use as biodegradable, biocompatible adhesives. Blends of low molecular weight (LMW) and high molecular weight (HMW) poly(lactide-co-caprolactone) (PLCL) are investigated as tissue adhesives in comparison to a clinical control. Wounds treated with PLCL blend adhesives heal completely with similar vascularization, scarring, and inflammation indicators, yet require fewer dressing changes due to integration of the PLCL adhesive into the wound. A blend of LMW and HMW PLCL produces an adhesive material with significantly higher adhesive strength than either neat polymer. Wound adhesion is comparable to a polyurethane bandage, utilizing conventional nonbiodegradable adhesives designed for extremely strong adhesion.

Viscoelastic blends of biodegradable polyesters with low and high molecular weight distributions have remarkably strong adhesion (significantly greater than 1 N/cm(2)) to soft, wet tissue. Those that transition from viscous flow to elastic, solidlike behavior at approximately 1 Hz demonstrate pressure-sensitivity yet also have sufficient elasticity for durable bonding to soft, wet tissue. The pressure-sensitive tissue adhesive (PSTA) blends produce increasingly stronger pull-apart adhesion in response to compressive pressure application, from 10 to 300 s. By incorporating a stiffer high molecular weight component, the PSTA exhibits dramatically improved burst pressure (greater than 100 kPa) when used as a tissue sealant. The PSTA's biodegradation mechanism can be switched from erosion (occurring primarily over the first 10 days) to bulk chemical degradation (and minimal erosion) depending on the chemistry of the high molecular weight component. Interestingly, fibrosis toward the PSTA is reduced when fast-occurring erosion is the dominant biodegradation mechanism.

The assembly of monodisperse particles into colloidal arrays that diffract visible light through constructive interference is of considerable interest due to their resilience against color fading. In particular, non-iridescent structurally colored materials are promising as a means of coloration for paints, inks, cosmetics, and displays because their color is angle-independent. A rapid and tunable assembly method for producing non-iridescent structurally colored colloidal-based materials that are pliable after fabrication is described. Structurally colored particle arrays were fabricated by centrifuging highly charged silica particles suspended in deionized water. By tuning the particle diameter, the colors displayed by the arrays spanned the visible spectrum while retaining angle-independent structural color. The color of centrifuged colloids of a single particle diameter was precisely controlled within 50 nm by modulating the particle concentration. The peak wavelength diffracted by the material was further tuned by altering the centrifugal rate and assembly time. Centrifugation assembly of particles in a polymer solution also produces non-iridescent colloidal films, and the control of their color is reported. Together, these results offer design considerations for the centrifugation-based assembly of colloidal films with tunable structural color that are transferable after fabrication and are angle-independent.

Abstract Conventional wound dressings are difficult to apply to large total body surface area (TBSA) wounds, as they typically are prefabricated, require a layer of adhesive coating for fixation, and need frequent replacement for entrapped exudate. Large TBSA wounds as well as orthopedic trauma and low‐resource surgery also have a high risk of infection. In this report, a sprayable and intrinsically adhesive wound dressing loaded with antimicrobial silver is investigated that provides personalized fabrication with minimal patient contact. The dressing is composed of adhesive and biodegradable poly(lactic‐co‐glycolic acid) and poly(ethylene glycol) (PLGA/PEG) blend fibers with or without silver salt (AgNO3). in vitro studies demonstrate that the PLGA/PEG/Ag dressing has antimicrobial properties and low cytotoxicity, with antimicrobial silver controllably released over 7–14 days. In a porcine partial‐thickness wound model, the wounds treated with both antimicrobial and nonantimicrobial PLGA/PEG dressings heal at rates similar to those of the clinical, thin film polyurethane wound dressing, with similar scarring. However, PLGA/PEG adds a number of features beneficial for wound healing: greater exudate absorption, integration into the wound, a 25% reduction in dressing changes, and tissue regeneration with greater vascularization. There is also modest improvement in epidermis thickness compared to the control wound dressing.

Commercially available surgical sealants for internal use either lack sufficient adhesion or produce cytotoxicity. This work describes a surgical sealant based on a polymer blend of poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) that increases wet tissue adherence by incorporation of nano-to-microscale silica particles, without significantly affecting cell viability, biodegradation rate, or local inflammation. In functional studies, PLGA/PEG/silica composite sealants produce intestinal burst pressures that are comparable to cyanoacrylate glue (160 mmHg), similar to 2 times greater than the non composite sealant (59 mmHg), and similar to 3 times greater than fibrin glue (49 mmHg). The addition of silica to PLGA/PEG is compatible with a sprayable in situ deposition method called solution blow spinning and decreases coagulation time in vitro and in vivo. These improvements are biocompatible and cause minimal additional inflammation, demonstrating the potential of a simple composite design to increase adhesion to wet tissue through physical, noncovalent mechanisms and enable use in procedures requiring simultaneous occlusion and hemostasis. Statement of Significance Incorporating silica particles increases the tissue adhesion of a polymer blend surgical sealant. The particles enable interfacial physical bonding with tissue and enhance the flexibility of the bulk of the sealant, without significantly affecting cytotoxicity, inflammation, or biodegradation. These studies also demonstrate how silica particles decrease blood coagulation time. This surgical sealant improves upon conventional devices because it can be easily deposited with accuracy directly onto the surgical site as a solid polymer fiber mat. The deposition method, solution blow spinning, allows for high loading in the composite fibers, which are sprayed from a polymer blend solution containing suspended silica particles. These findings could easily be translated to other implantable or wearable devices due to the versatility of silica particles. (C) 2019 Published by Elsevier Ltd on behalf of Acta Materialia Inc.

A tunable protease responsive nanoparticle hydrogel (PRNH) that demonstrates large non-iridescent color changes due to a degradation-directed assembly of nanoparticles is reported. Structurally colored composites are fabricated with silica particles, 4-arm poly(ethylene glycol) norbornene (4PEGN), and a proteolytically degradable peptide. When placed in a protease solution, the peptide crosslinks degrade causing electrostatic binding and adsorption of the polymer to the particle surface which leads to the assembly of particles into compact amorphous arrays with structural color. The particle surface charge and size is investigated to probe their effect on the assembly mechanism. Interestingly, only PRNHs with highly negative particle surface charge exhibit color changes after degradation. Ultra-small angle X-ray scattering revealed that the particles become coated in polymer after degradation, producing a material with less order compared to the initial state. Altering the particle diameter modulates the composites' color, and all sizes investigated (178-297 nm) undergo the degradation-directed assembly. Varying the amount of 4PEGN adjusts the swollen PRNH color and has no effect on the degradation-directed assembly. Taken together, the effects of surface charge, particle size, and polymer concentration allow for the formulation of new design rules for fabricating tunable PRNHs that display vivid changes in structural color upon degradation.

A new report identifies missing support that is slowing progress in limiting and adapting to climate change. The Science for Climate Action Network aims to provide it.

Highly conductive elastic composites were constructed using multistep solution-based fabrication methods that included the deposition of a nonwoven polymer fiber mat through solution blow spinning and nanoparticle nucleation. High nanoparticle loading was achieved by introducing silver nanoparticles into the fiber spinning solution. The presence of the silver nanoparticles facilitates improved uptake of silver nanoparticle precursor in subsequent processing steps. The precursor is used to generate a second nanoparticle population, leading to high loading and conductivity. Establishing high nanoparticle loading in a microfibrous block copolymer network generated deformable composites that can sustain electrical conductivities reaching 9000 S/cm under 100% tensile strain. These conductive elastic fabrics can retain at least 70% of their initial electrical conductivity after being stretched to 100% strain and released for 500 cycles. This composite material system has the potential to be implemented in wearable electronics and robotic systems.

Fibroblast growth factor-21 (FGF21) levels are elevated in patients with primary mitochondrial disorders but have not been studied in patients with inborn errors of metabolism (IEM) known to have secondary mitochondrial dysfunction. We measured plasma FGF21 by ELISA in patients with and without IEM. FGF21 levels were higher in patients with IEM compared to without IEM (370 pg/dL vs. 0-65 pg/dL). Further study of FGF21 as a biomarker in IEM is warranted.

Hyperphenylalaninemia (HPA) is a disorder diagnosed only incidentally by newborn screening, a by-product of screening for classic phenylketonuria (PKU) which, if untreated, causes irreversible neurologic sequelae. In contrast, HPA is thought to have a benign phenotype because phenylalanine (Phe) levels are insufficiently elevated to cause neurological damage, obviating the need for rigorous dietary protein restriction. Phenylalanine below 360 mu mol/L is generally considered safe, thus this threshold is both the upper therapeutic range for treated PKU and the highest Phe expected to be possible for most individuals with HPA. However, the published literature and even expert consensus provides limited guidance on long-term follow-up of Phe after this diagnosis. In particular, how frequently and vigilantly to monitor levels to evaluate for subsequent elevations above the 'safe' range. Upon retrospective review we identified 22 patients with HPA, ascertained via newborn screen and currently aged two to thirty-six years. All patients had an initial untreated Phe between 90 mu mol/L (our upper limit of normal) and 360 mu mol/L. Of these patients, seven subsequently demonstrated either fluctuating or sustained increases in Phe above 360 mu mol/L. Five have been treated successfully with sapropterin therapy without dietary intervention and two have been treated with mild to moderate protein restriction. Our experience demonstrates successful treatment of these children without the traditional highly restrictive PKU diet. However, a better understanding of this disorder is necessary to more safely and appropriately identify, monitor and manage children with HPA. Synopsis: One clinics' experience with diagnostic differences in a population of Hyperphenylalaninemia patients that required treatment.

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates. We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine analysis. Treatment was started immediately. Acylcarnitine analysis demonstrated findings that are consistent with a biochemical diagnosis of LCHAD/TFP deficiency. Patients with LCHAD/TFP deficiency should have treatment initiated as early as possible to avoid acute decompensation and minimize the long-term complications of the disorder including cardiomyopathy. In pregnancies at risk of having a child with LCHAD/TFP deficiency, umbilical cord blood sample is an efficient method to diagnose an inborn error of metabolism such as LCHAD/TFP deficiency.

Quantification of ammonia in whole blood has applications in the diagnosis and management of many hepatic diseases, including cirrhosis and rare urea cycle disorders, amounting to more than 5 million patients in the United States. Current techniques for ammonia measurement suffer from limited range, poor resolution, false positives or large, complex sensor set-ups. Here we demonstrate a technique utilizing inexpensive reagents and simple methods for quantifying ammonia in 100 μL of whole blood. The sensor comprises a modified form of the indophenol reaction, which resists sources of destructive interference in blood, in conjunction with a cation-exchange membrane. The presented sensing scheme is selective against other amine containing molecules such as amino acids and has a shelf life of at least 50 days. Additionally, the resulting system has high sensitivity and allows for the accurate reliable quantification of ammonia in whole human blood samples at a minimum range of 25 to 500 μM, which is clinically for rare hyperammonemic disorders and liver disease. Furthermore, concentrations of 50 and 100 μM ammonia could be reliably discerned with p = 0.0001.

The passive monitoring of biological environments by soft materials has a variety of nanobiotechnology applications; however, invoking distinct transitions in geometric, mechanical or optical properties remains a prevalent design challenge. We demonstrate here that close-packed nanoparticle-hydrogel composites can progress through a substantial shift in such properties by the use of a chemical-to-physical cross-link transition mediated by the catalytic activity of different proteases. Catalytic cleavage of the original hydrogel network structure initiates the self-assembled formation of a secondary, physically cross-linked network, causing a 1200% increase in storage modulus. Furthermore, this unique mechanism can be fabricated as a 3D photonic crystal with broad (∼240 nm), visible responses to the targeted enzymes. Moreover, the material provided threshold responses, requiring a certain extent of proteolytic activity before the transition occurred. This allowed for the fabrication of Boolean logic gates (OR and AND), which responded to a specific assortment of proteases. Ultimately, this mechanism enables the design of stimuli-responsive hydrogels, which can proceed through a secondary network formation, after an energetic barrier has been breached. Protease responsive hydrogel nanocomposites, described here, could offer avenues in degradation-stiffening and collapsing materials for a variety of biomaterial applications.