A new perspective when examining maize fertilizer nitrogen use efficiency, incrementally.

For maize (Zea mays L.), nitrogen (N) fertilizer use is often summarized from field to global scales using average N use efficiency (NUE). But expressing NUE as averages is misleading because grain increase to added N diminishes near optimal yield. Thus, environmental risks increase as economic benefits decrease. Here, we use empirical datasets obtained in North America of maize grain yield response to N fertilizer (n = 189) to create and interpret incremental NUE (iNUE), or the change in NUE with change in N fertilization. We show for those last units of N applied to reach economic optimal N rate (EONR) iNUE for N removed with the grain is only about 6%. Conversely stated, for those last units of N applied over 90% is either lost to the environment during the growing season, remains as inorganic soil N that too may be lost after the growing season, or has been captured within maize stover and roots or soil organic matter pools. Results also showed iNUE decrease averaged 0.63% for medium-textured soils and 0.37% for fine-textured soils, attributable to fine-textured soils being more predisposed to denitrification and/or lower mineralization. Further analysis demonstrated the critical nature growing season water amount and distribution has on iNUE. Conditions with too much rainfall and/or uneven rainfall produced low iNUE. Producers realize this from experience, and it is uncertain weather that largely drives insurance fertilizer additions. Nitrogen fertilization creating low iNUE is environmentally problematic. Our results show that with modest sub-EONR fertilization and minor forgone profit, average NUE improvements of ~10% can be realized. Further, examining iNUE creates unique perspective and ideas for how to improve N fertilizer management tools, educational programs, and public policies and regulations.

Predicting Young's Modulus of Linear Polyurethane and Polyurethane-Polyurea Elastomers: Bridging Length Scales with Physicochemical Modeling and Machine Learning.

Predicting the properties of complex polymeric materials based on monomer chemistry requires modeling physical interactions that bridge molecular, interchain, microstructure, and bulk length scales. For polyurethanes, a polymer class with global commercial and industrial significance, these multiscale challenges are intrinsic due to the thermodynamic incompatibility of the urethane and polyol-rich domains, resulting in heterogeneities from molecular to microstructural length scales. Machine learning can model patterns in data to establish a relationship between the monomer chemistry and bulk material properties, but this is made difficult by small data sets and a diverse set of monomers. Using a data set of 63 industrially relevant and complex elastomers, we demonstrate that accurate machine learning predictions are possible when monomer chemistry is used to estimate interactions at interchain length scales. Here, these features were used to accurately (r2 = 0.91) predict the Young's modulus of polyurethane and polyurethane-urea elastomers. Furthermore, by a query of the trained model for compositions that yield a target modulus within the range of accessible values, the capabilities of using this methodology as a design tool are demonstrated. The presented methodology could become increasingly useful in building models for materials with small data sets and may guide the interpretation of the underlying physicochemical forces.

CoLabS: A collaborative space for transdisciplinary work in sustainable community development.

Currently, the need for transdisciplinary approaches and collaboration, to reduce the gap between science and practice, is continuously rising along with the need for sustainable development. An increase in knowledge transfer, meetings and overall communication among researchers and practitioners is a logical consequence of the previous. However, the resulting higher transaction costs, mainly related to transportation-related greenhouse gas emissions (and additional financial costs) involved in face-to-face meetings, are in direct conflict with the urgent need to reduce our carbon footprint. This research explored the development of an online platform, "CoLabS", specifically designed as a virtual meeting and learning space to support collaboration within and between communities to accelerate sustainable community development efforts. While the move towards online collaboration in virtual environments has steadily increased in the past decade, it has now become essential due to the COVID-19 pandemic. Based on the feedback provided by focus groups, the collaboratory platform's design and usability as well as the technical aspects and its functionality are discussed in this paper.

Hierarchical Machine Learning for High-Fidelity 3D Printed Biopolymers.

A hierarchical machine learning (HML) framework is presented that uses a small dataset to learn and predict the dominant build parameters necessary to print high-fidelity 3D features of alginate hydrogels. We examine the 3D printing of soft hydrogel forms printed with the freeform reversible embedding of suspended hydrogel method based on a CAD file that isolated the single-strand diameter and shape fidelity of printed alginate. Combinations of system variables ranging from print speed, flow rate, ink concentration to nozzle diameter were systematically varied to generate a small dataset of 48 prints. Prints were imaged and scored according to their dimensional similarity to the CAD file, and high print fidelity was defined as prints with less than 10% error from the CAD file. As a part of the HML framework, statistical inference was performed, using the least absolute shrinkage and selection operator to find the dominant variables that drive the error in the final prints. Model fit between the system parameters and print score was elucidated and improved by a parameterized middle layer of variable relationships which showed good performance between the predicted and observed data (R2 = 0.643). Optimization allowed for the prediction of build parameters that gave rise to high-fidelity prints of the measured features. A trade-off was identified when optimizing for the fidelity of different features printed within the same construct, showing the need for complex predictive design tools. A combination of known and discovered relationships was used to generate process maps for the 3D bioprinting designer that show error minimums based on the chosen input variables. Our approach offers a promising pathway toward scaling 3D bioprinting by optimizing print fidelity via learned build parameters that reduce the need for iterative testing.

Elucidating the Physicochemical Basis of the Glass Transition Temperature in Linear Polyurethane Elastomers with Machine Learning.

The glass transition temperature (Tg) is a fundamental property of polymers that strongly influences both mechanical and flow characteristics of the material. In many important polymers, configurational entropy of side chains is a dominant factor determining it. In contrast, the thermal transition in polyurethanes is thought to be determined by a combination of steric and electronic factors from the dispersed hard segments within the soft segment medium. Here, we present a machine learning model for the Tg in linear polyurethanes and aim to uncover the underlying physicochemical parameters that determine this. The model was trained on literature data from 43 industrially relevant combinations of polyols and isocyanates using descriptors derived from quantum chemistry, cheminformatics, and solution thermodynamics forming the feature space. Random forest and regularized regression were then compared to build a sparse linear model from six descriptors. Consistent with empirical understanding of polyurethane chemistry, this study indicates the characteristics of isocyanate monomers strongly determine the increase in Tg. Accurate predictions of Tg from the model are demonstrated, and the significance of the features is discussed. The results suggest that the tools of machine learning can provide both physical insights as well as accurate predictions of complex material properties.

Adsorption kinetics, thermodynamics, and isotherm studies for functionalized lanthanide-chelating resins.

Conventional ion exchange resins are widely utilized to remove metals from aqueous solutions, but their limited selectivity precludes dilute ion extraction. This research investigated the adsorption performance of ligand-functionalized resins towards rare earth elements (REE). Functionalized resin particles were synthesized by grafting different ligands (diethylenetriaminepentaacetic dianhydride (DTPADA), phosphonoacetic acid (PAA), or N,N-bis(phosphonomethyl)glycine (BPG)) onto pre-aminated polymeric adsorbents (diameter ∼ 0.6 mm). Lanthanide uptake trends were evaluated for the functionalized resins using batch adsorption experiments with a mixture of three REEs (Nd, Gd, and Ho at 0.1-1000 mg/L each). Resin physical-chemical properties were determined by measuring their surface area, ligand concentrations, and acidity constants. The aminated supports contained 4.0 mmol/g primary amines, and ligand densities for the functionalized resins were 0.33 mmol/g (PAA), 0.22 mmol/g (BPG), and 0.42 mmol/g (DTPADA). Kinetic studies revealed that the functionalized resins followed pseudo-second order binding kinetics with rates limited by intraparticle diffusion. Capacity estimates for total REE adsorption based on Langmuir qMax were 0.12 mg/g (amine; ≈ 0.77 µmol/g), 5.0 mg/g (PAA; ≈ 32.16 µmol/g), 3.0 mg/g (BPG; ≈ 19.30 µmol/g), and 2.9 mg/g (DTPADA; ≈ 18.65 µmol/g). Attaching ligands to the aminated resins greatly improved their REE binding strength and adsorption efficiency.

Transport patterns of anti-TNF-α in burn wounds: Therapeutic implications of hyaluronic acid conjugation.

A central complication in burn injuries is progression of the zone of necrosis, which is associated with intense inflammatory responses. Conjugation of monoclonal antibodies against tumor necrosis factor-α (TNF-α), a central mediator of inflammation, to high molecular weight hyaluronic acid (HA) has been shown to be an effective treatment in reducing secondary necrosis in rodent models of deep partial-thickness burns. Here the transport of conjugated and non-conjugated antibodies in burn injuries was investigated to explore the effects of antibody tethering on the spatiotemporal distribution of anti-TNF-α. Diffusion constants were measured in solution and in type I collagen gels in vitro using fluorescence correlation spectroscopy to provide quantitative comparisons of the effects of conjugation. It is shown that the HA significantly increased the antibody residence time in the superficial region at 24 h in burn injuries, which strongly correlated with the pattern of inflammatory cell infiltrate in the tissue. A transport model was used to fit the results of antibody distribution in the tissue based on fluorescence correlation spectroscopy measurements, resulting in estimates for effective diffusion constants that demonstrate the effects of HA conjugation on the biodistribution of therapeutic proteins. These results demonstrate that tuning residence time of therapeutic proteins can be an effective strategy in regulating the inflammatory response associated with acute injuries.

Tip-Loaded Dissolvable Microneedle Arrays Effectively Deliver Polymer-Conjugated Antibody Inhibitors of Tumor-Necrosis-Factor-Alpha Into Human Skin.

Autoinflammatory skin diseases are characterized by a disequilibrium of cytokines in the local skin microenvironment, suggesting that local delivery of therapeutics, including anticytokine antibodies, may provide benefit without the unwanted off-target effects of systemically delivered therapies. Rapid diffusion of therapeutics away from the target site has been a challenge to the development of local therapies. Conjugation of high molecular weight hydrophilic polymers to cytokine neutralizing mAbs has been shown to be an effective strategy for local control of inflammation in healing burn wounds. However, the burn application is unique because the skin barrier is already breached. For the treatment of autoinflammatory skin diseases, the major challenge for local delivery lies in penetrating the stratum corneum. Here, we investigate a new therapeutic approach combining the use of tip-loaded dissolvable microneedle arrays (TL-dMNAs) for local application of polymer-conjugated antibody inhibitors of tumor-necrosis-factor-alpha (TNF-α). Specifically, intradermal delivery and pharmacokinetics of (anti-TNF-α-Ab)-(high molecular weight hyaluronic acid [HA]) conjugates from tip-loaded, obelisk-shaped dissolvable microneedle arrays were investigated in living human skin. The results indicate (1) TL-dMNAs can be successfully fabricated to integrate (anti-TNF-α-Ab)-HA at the tip portion of the microneedles while preserving the biological activity necessary for antibody ligand binding; (2) (anti-TNF-α-Ab)-HA can be effectively delivered into human skin using obelisk-shaped TL-dMNAs; and (3) polymer conjugation effectively inhibits antibody diffusion from the delivery site. Taken together, these results support the evaluation of microneedle array-based delivery of varying polymer-antibody conjugates for the treatment of inflammatory skin diseases.

Tunable Pickering emulsions with polymer-grafted lignin nanoparticles (PGLNs).

Lignin is an abundant biopolymer that has native interfacial functions but aggregates strongly in aqueous media. Polyacrylamide was grafted onto kraft lignin nanoparticles using reversible addition-fragmentation chain transfer (RAFT) chemistry to form polymer-grafted lignin nanoparticles (PGLNs) that tune aggregation strength while retaining interfacial activities in forming Pickering emulsions. Polymer graft density on the particle surface, ionic strength, and initial water and cyclohexane volume fractions were varied and found to have profound effects on emulsion characteristics, including emulsion volume fraction, droplet size, and particle interfacial concentration that were attributed to changes in lignin aggregation and hydrophobic interactions. In particular, salt concentration was found to have a significant effect on aggregation, zeta potential, and interfacial tension, which was attributed to changes in solubility of both the kraft lignin and the polyacrylamide grafts. Dynamic light scattering, UV-vis spectroscopy, optical microscopy, and tensiometry were used to quantify emulsion properties and nanoparticle behavior. Under all conditions, the emulsions exhibited relatively fast creaming but were stable against coalescence and Ostwald ripening for a period of months. All emulsions were also oil-in-water (o/w) emulsions, as predicted by the Bancroft rule, and no catastrophic phase inversions were observed for any nanoparticle compositions. We conclude that lower grafting density of polyacrylamide on a lignin core resulted in high levels of interfacial activity, as characterized by higher concentration at the water-cyclohexane interface with a corresponding decrease in interfacial tension. These results indicate that the interfacial properties of polymer-grafted lignin nanoparticles are primarily due to the native hydrophobic interactions of the lignin core. These results suggest that the forces that drive aggregation are also correlated with interfacial activities, and polymer-nanoparticle interactions are critical for optimizing interfacial activities. Controlled radical polymerization is a powerful tool for polymer grafting that can leverage the intrinsic interfacial functions of lignin for the formation of Pickering emulsions.

Lignopolymers as viscosity-reducing additives in magnesium oxide suspensions.

Lignopolymers are a new class of polymer additives with the capability to be used as dispersants in cementitious pastes. Made with kraft lignin cores and grafted polymer side-chains, the custom-synthesized lignopolymers were examined in terms of the molecular architecture for viscosity reducing potential in inert model suspensions. Lignin-poly(acrylic acid) (LPAA) and lignin-polyacrylamide (LPAm) have been found to vary the rheology of magnesium oxide (MgO) suspensions based on differences in chain architecture and particle-polymer interactions. A commercial comb-polymer polycarboxylate ester was compared to LPAA and LPAm at 2.7 mg/mL, a typical dosage for cement admixtures, as well as 0.25mg/mL. It was found that LPAm was a more effective viscosity reducer than both LPAA and the commercial additive at low concentrations, which was attributed to greater adsorption on the MgO particle surface and increased steric dispersion from PAm side-chain extension. The influence of chain adsorption and grafted side-chain molecular weight on rheology was also tested.

Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays.

Tumor necrosis factor-alpha (TNF-α) specific antibodies (anti-TNF-α Ab) have been shown to be potent TNF inhibitors and effective therapeutics for a range of inflammatory diseases. Typically, these drugs are administered systemically, but systemic dosing sufficient to achieve locally effective concentrations in peripheral tissues has been associated with systemic immunosuppression and related adverse events. Here, we evaluated the use of tip-loaded dissolvable microneedle arrays (MNAs) for localized intradermal delivery of anti-TNF-α Ab. MNAs with obelisk shape microneedles that incorporate the antibody cargo in the needle tips were created from carboxymethylcellulose (CMC) using a micromilling/spin-casting fabrication method. We found that anti-TNF-α Ab integrated into MNAs using this room temperature fabrication process maintained conformationally dependent TNF-α binding activity. Further, these MNAs efficiently delivered anti-TNF-α antibodies to the dermis of human skin with clinically applicable release profiles. To evaluate MNA delivered anti-TNF-α Ab function, we applied anti-TNF-α Ab containing MNAs to established psoriasiform lesions on the skin of mice. MNA anti-TNF-α Ab treatment reduced key biomarkers of psoriasiform inflammation including epidermal thickness and IL-1ß expression. Taken together, these results demonstrate efficient and biologically effective MNA delivery of anti-TNF-α Ab to the intradermal microenvironment of the skin in mice and humans, and support the development of MNA mediated antibody delivery for clinical applications. STATEMENT OF SIGNIFICANCE: Tumor necrosis factor-alpha (TNF-α) specific antibodies (anti-TNF-α Ab) have been shown to be potent TNF inhibitors and effective therapeutics for a range of inflammatory diseases. Typically, these drugs are administered systemically, but systemic dosing sufficient to achieve locally effective concentrations in peripheral tissues has been associated with systemic immunosuppression and related adverse events. Here we demonstrate efficient and biologically effective MNA delivery of anti-TNF-α Ab to the intradermal microenvironment of the skin in mice and humans. These results support the development of MNA mediated antibody delivery of therapeutic antibodies for clinical applications.

Molecular architecture requirements for polymer-grafted lignin superplasticizers.

Superplasticizers are a class of anionic polymer dispersants used to inhibit aggregation in hydraulic cement, lowering the yield stress of cement pastes to improve workability and reduce water requirements. The plant-derived biopolymer lignin is commonly used as a low-cost/low-performance plasticizer, but attempts to improve its effects on cement rheology through copolymerization with synthetic monomers have not led to significant improvements. Here we demonstrate that kraft lignin can form the basis for high-performance superplasticizers in hydraulic cement, but the molecular architecture must be based on a lignin core with a synthetic-polymer corona that can be produced via controlled radical polymerization. Using slump tests of ordinary Portland cement pastes, we show that polyacrylamide-grafted lignin prepared via reversible addition-fragmentation chain transfer polymerization can reduce the yield stress of cement paste to similar levels as a leading commercial polycarboxylate ether superplasticizer at concentrations ten-fold lower, although the lignin material produced via controlled radical polymerization does not appear to reduce the dynamic viscosity of cement paste as effectively as the polycarboxylate superplasticizer, despite having a similar affinity for the individual mineral components of ordinary Portland cement. In contrast, polyacrylamide copolymerized with a methacrylated kraft lignin via conventional free radical polymerization having a similar overall composition did not reduce the yield stress or the viscosity of cement pastes. While further work is required to elucidate the mechanism of this effect, these results indicate that controlling the architecture of polymer-grafted lignin can significantly enhance its performance as a superplasticizer for cement.

Long-term agroecosystem research in the central Mississippi river basin: introduction, establishment, and overview.

Many challenges currently facing agriculture require long-term data on landscape-scale hydrologic responses to weather, such as from the Goodwater Creek Experimental Watershed (GCEW), located in northeastern Missouri, USA. This watershed is prone to surface runoff despite shallow slopes, as a result of a significant smectitic clay layer 30 to 50 cm deep that restricts downward flow of water and gives rise to a periodic perched water table. This paper is the first in a series that documents the database developed from GCEW. The objectives of this paper are to (i) establish the context of long-term data and the federal infrastructure that provides it, (ii) describe the GCEW/ Central Mississippi River Basin (CMRB) establishment and the geophysical and anthropogenic context, (iii) summarize in brief the collected research results published using data from within GCEW, (iv) describe the series of papers this work introduces, and (v) identify knowledge gaps and research needs. The rationale for the collection derives from converging trends in data from long-term research, integration of multiple disciplines, and increasing public awareness of increasingly larger problems. The outcome of those trends includes being selected as the CMRB site in the USDA-ARS Long-Term Agro-Ecosystem Research (LTAR) network. Research needs include quantifying watershed scale fluxes of N, P, K, sediment, and energy, accounting for fluxes involving forest, livestock, and anthropogenic sources, scaling from near-term point-scale results to increasingly long and broad scales, and considering whole-system interactions. This special section informs the scientific community about this database and provides support for its future use in research to solve natural resource problems important to US agricultural, environmental, and science policy.

Long-term agroecosystem research in the central Mississippi river basin: hydrogeologic controls and crop management influence on nitrates in loess and fractured glacial till.

Nitrogen from agriculture is known to be a primary source of groundwater NO-N. Research was conducted in a northeastern Missouri watershed to assess the impact of cropping systems on NO-N for a loess and fractured glacial till aquifer underlying claypan soils. Three cropped fields with 10 yr of similar management were each instrumented with 20 to 25 monitoring wells, 3 to 15 m in depth, in 1991 to 1992. Wells were sampled and analyzed for NO-N at least annually from 1991 to 2004. Initial NO-N concentrations were variable, ranging from undetectable to >24 mg L but averaged 7.0 mg L. Groundwater NO-N was significantly higher in Field 3, probably the result of concurrent applications of manure and N fertilizer before 1980. Overall changes in NO-N levels in Fields 1 and 2 were generally small; however, NO-N levels for Field 3 have decreased an average of 0.28 mg L yr. Excessive loading of N into the matrix of the glacial till may have had a long-term impact on NO-N for this field. Despite the presence of dissolved O in the aquifer, evidence of denitrification in some upper-landscape groundwater wells was found. The greatest decreases in NO-N concentration occurred as groundwater moved through an in-field tree line or through a riparian zone. While overall conclusions were complicated by the long-term impact of past management, the capacity of the till to buffer changes, hydrogeologic variability found among wells, and the activity of biological processes, we conclude that cropping practices during this study did not increase glacial till NO-N.

Local delivery of antitumor necrosis factor-α through conjugation to hyaluronic acid: dosing strategies and early healing effects in a rat burn model.

The objective of this study was to measure dose-response effects of topical delivery of inhibitors of tumor necrosis factor-α (TNF-α) through conjugation to hyaluronic acid in a rat burn model to determine effects on inflammatory responses, burn progression, and early stages of healing. Monoclonal antibodies against TNF-α were conjugated to hyaluronic acid and applied topically in a rat partial-thickness burn model. Metrics of inflammatory responses and tissue necrosis were measured as well as the quantitative analysis of collagen composition and organization. The minimum effective conjugated antibody dose was found to be 100 µg with three applications 48 hours apart. Nonviable tissue thicknesses decreased with increasing dose and dose frequency. Free antibody retarded macrophage infiltration in the periphery but not at the surface, while the conjugated antibody was able to hinder macrophage infiltration at both the periphery and the surface. Quantification of collagen I and III staining ratios at days 4, 7, and 14 and quantitative image analysis of collagen organization at day 14 demonstrated differences between saline and conjugate treatment. This correlated with increases in re-epithelialization observed in conjugate-treated sites. Reductions in inflammatory markers and secondary tissue necrosis under treatment with the conjugates were understood in terms of differences in antibody transport compared to nonconjugated antibody. Differences in collagen composition and organization at Day 14 suggested that the reductions in inflammatory responses altered early healing responses. These results indicate anti-TNF-α conjugated to hyaluronic acid can be an effective treatment for reducing secondary necrosis and improving healing outcomes in burns.

Polymer-grafted lignin surfactants prepared via reversible addition-fragmentation chain-transfer polymerization.

Kraft lignin grafted with hydrophilic polymers has been prepared using reversible addition-fragmentation chain-transfer (RAFT) polymerization and investigated for use as a surfactant. In this preliminary study, polyacrylamide and poly(acrylic acid) were grafted from a lignin RAFT macroinitiator at average initiator site densities estimated to be 2 per particle and 17 per particle. The target degrees of polymerization were 50 and 100, but analysis of cleaved polyacrylamide was consistent with a higher average molecular weight, suggesting not all sites were able to participate in the polymerization. All materials were readily soluble in water, and dynamic light scattering data indicate polymer-grafted lignin coexisted in isolated and aggregated forms in aqueous media. The characteristic size was 15-20 nm at low concentrations, and aggregation appeared to be a stronger function of degree of polymerization than graft density. These species were surface active, reducing the surface tension to as low as 60 dyn/cm at 1 mg/mL, and a greater decrease was observed than for polymer-grafted silica nanoparticles, suggesting that the lignin core was also surface active. While these lignin surfactants were soluble in water, they were not soluble in hexanes. Thus, it was unexpected that water-in-oil emulsions formed in all surfactant compositions and solvent ratios tested, with average droplet sizes of 10-20 µm. However, although polymer-grafted lignin has structural features similar to nanoparticles used in Pickering emulsions, its interfacial behavior was qualitatively different. While at air-water interfaces, the hydrophilic grafts promote effective reductions in surface tension, we hypothesize that the low grafting density in these lignin surfactants favors partitioning into the hexanes side of the oil-water interface because collapsed conformations of the polymer grafts improve interfacial coverage and reduce water-hexanes interactions. We propose that polymer-grafted lignin surfactants can be considered as random patchy nanoparticles with mixed hydrophilic and hydrophobic domains that result in unexpected interfacial behaviors. Further studies are necessary to clarify the molecular basis of these phenomena, but grafting of hydrophilic polymers from kraft lignin via radical polymerization could expand the use of this important biopolymer in a broad range of surfactant applications.

Reducing protein adsorption with polymer-grafted hyaluronic acid coatings.

We report a thermoresponsive chemical modification strategy of hyaluronic acid (HA) for coating onto a broad range of biomaterials without relying on chemical functionalization of the surface. Poly(di(ethylene glycol) methyl ether methacrylate) (PMEO2MA), a polymer with a lower critical solution temperature of 26 °C in water, was grafted onto HA to allow facile formation of biopolymer coatings. While the mechanism for film formation appears to involve a complex combination of homogeneous nucleation followed by heterogeneous film growth, we demonstrate that it resulted in hydrophilic coatings that significantly reduce protein adsorption despite the high fraction of hydrophobic (PMEO2MA). Structural characterization was performed using atomic force microscopy (AFM), which showed the formation of a dense, continuous coating based on 200 nm domains that were stable in protein solutions for at least 15 days. The coatings had a water contact angle of 16°, suggesting the formation of hydrophilic but not fully wetting films. Quartz crystal microbalance with dissipation monitoring (QCM-D) as well as biolayer interferometry (BLI) techniques were used to measure adsorption of bovine serum albumin (BSA), fibrinogen (Fbg), and human immunoglobulin (IgG), with results indicating that HA-PMEO2MA-coated surfaces effectively inhibited adsorption of all three serum proteins. These results are consistent with previous studies demonstrating that this degree of hydrophilicity is sufficient to generate an effectively nonfouling surface and suggest that segregation during the solubility transition resulted in a surface that presented the hydrophilic HA component of the hybrid biopolymer. We conclude that PMEO2MA-grafted HA is a versatile platform for the passivation of hydrophobic biomaterial surfaces without need for substrate functionalization.

Electrocatalytic oxygen evolution with an immobilized TAML activator.

Iron complexes of tetra-amido macrocyclic ligands are important members of the suite of oxidation catalysts known as TAML activators. TAML activators are known to be fast homogeneous water oxidation (WO) catalysts, producing oxygen in the presence of chemical oxidants, e.g., ceric ammonium nitrate. These homogeneous systems exhibited low turnover numbers (TONs). Here we demonstrate immobilization on glassy carbon and carbon paper in an ink composed of the prototype TAML activator, carbon black, and Nafion and the subsequent use of this composition in heterogeneous electrocatalytic WO. The immobilized TAML system is shown to readily produce O2 with much higher TONs than the homogeneous predecessors.

Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns.

Biomaterials capable of neutralizing specific cytokines could form the basis for treating a broad range of conditions characterized by intense, local inflammation. Severe burns, spanning partial- to full-thickness of the dermis, can result in complications due to acute inflammation that contributes to burn progression, and early mediation may be a key factor in rescuing thermally injured tissue from secondary necrosis to improve healing outcomes. In this work, we examined the effects on burn progression and influence on the inflammatory microenvironment of topical application of anti-tumor necrosis factor-α (anti-TNF-α) alone, mixed with hyaluronic acid (HA) or conjugated to HA. We found that non-conjugated anti-TNF-α decreased macrophage infiltration to a greater extent than that conjugated to HA; however, there was little effect on the degree of progression or IL-1ß levels. A simple transport model is proposed to analyze the results, which predicts qualitative and quantitative differences between untreated burn sites and those treated with the conjugates. Our results indicate that conjugation of anti-TNF-α to high molecular weight HA provides sustained, local modulation of the post-injury inflammatory responses compared to direct administration of non-conjugated antibodies.

Polymer-conjugated inhibitors of tumor necrosis factor-α for local control of inflammation.

Burns, chronic wounds, osteoarthritis, and uveitis are examples of conditions characterized by local, intense inflammatory responses that can impede healing or even further tissue degradation. The most powerful anti-inflammatory drugs available are often administered systemically, but these carry significant side effects and are not compatible for patients that have underlying complications associated with their condition. Conjugation of monoclonal antibodies that neutralize pro-inflammatory cytokines to high molecular weight hydrophilic polymers has been shown to be an effective strategy for local control of inflammation. Lead formulations are based on antibody inhibitors of tumor necrosis factor-α conjugated to hyaluronic acid having molecular weight greater than 1 MDa. This review will discuss fundamental aspects of medical conditions that could be treated with these conjugates and design principles for preparing these cytokine-neutralizing polymer conjugates. Results demonstrating that infliximab, an approved inhibitor of tumor necrosis factor-α, can be incorporated into the conjugates using a broad range of water-soluble polymers are also presented, along with a prospectus for clinical translation.