Co-reporter:Chetali Gupta and Newell R. Washburn
Langmuir August 12, 2014 Volume 30(Issue 31) pp:9303-9312
Publication Date(Web):August 12, 2014
DOI:10.1021/la501696y
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.
Co-reporter:Kedar M. Perkins, Chetali Gupta, Emily N. Charleson, Newell R. Washburn
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2017 Volume 530(Volume 530) pp:
Publication Date(Web):5 October 2017
DOI:10.1016/j.colsurfa.2017.07.061
Lignin is a biopolymer in plant cell walls that has intrinsic interfacial functions and is produced in vast quantities but has found limited application as a surfactant. Here we demonstrate that low-density functionalization of anionic lignin derivatives with a corona of poly(ethylene glycol) (PEG) significantly augments their native interfacial activities, in contrast to previous studies of PEGylated lignins in which extensive functionalization was performed based on hydrophilic-lipophilic balance (HLB) predictions of solubility. Commercially available kraft lignin and lignosulfonate having high concentrations of carboxylate and sulfonate groups, respectively, were PEGylated with monoreactive grafts having molecular weight 750, 2000, and 5000 g/mol at constant grafting density and PEG fractions as low as 20% for the 750 g/mol species whereas previous studies focused on 50% PEGylation of greater. Both classes of PEGylated lignin demonstrated modest reductions in air-water surface tension, which decreased monotonically with PEGylated lignin concentration to values as low as 50 dyn/cm but did not demonstrate a sharp critical micelle concentration (CMC). However, the air-water surface tension was found to be relatively insensitive to both the chemistry of the lignin core and the graft length. In contrast, the cyclohexane-water interfacial tension was strongly dependent on lignin core, graft length, and concentration, with PEGylated kraft lignin driving the interfacial tension value to 3 dyn/cm at a concentration of 0.1 mg/mL that corresponded with an apparent critical micelle concentration while the PEGylated lignosulfonates had a weaker effect, with uniformly higher values of interfacial tension measured and no CMC observed. Finally, cyclohexane-water emulsions were prepared, and the volume fraction of the emulsion phase was much greater for PEGylated kraft lignin than for PEGylated lignosulfonate, suggesting formulations based on kraft lignin are significantly more effective at stabilizing oil-water interfaces. This disparity suggests that specific interactions between the lignin core and the non-aqueous phase may augment interfacial activities.Download high-res image (159KB)Download full-size image
Co-reporter:Aditya Menon;Chetali Gupta;Kedar M. Perkins;Brian L. DeCost;Nikita Budwal;Renee T. Rios;Kun Zhang;Barnabás Póczos
Molecular Systems Design & Engineering (2016-Present) 2017 vol. 2(Issue 3) pp:263-273
Publication Date(Web):2017/08/07
DOI:10.1039/C7ME00027H
A computational method for understanding and optimizing the properties of complex physical systems is presented using polymeric dispersants as an example. Concentrated suspensions are formulated with dispersants to tune rheological parameters, such as yield stress or viscosity, but their competing effects on solution and particle variables have made it impossible to design them based on our knowledge of the interplay of chemistry and function. Here, physical and statistical modeling are integrated into a hierarchical framework of machine learning that provides insight into sparse experimental datasets. A library of 10 polymers having similar molecular weight but incorporating different functional groups commonly found in aqueous dispersants was used as a training set in magnesium oxide slurries. The compositions of these polymers were the experimental variables that determined the complex system responses, but the method leverages knowledge of the constituent “single-physics” interactions that underlie the suspension properties. Integration of domain knowledge is shown to allow robust predictions based on orders of magnitude fewer samples in the training set compared with purely statistical methods that directly correlate dispersant chemistry with changes in rheological properties. Minimization of the resulting function for slurry yield stress resulted in the prediction of a novel dispersant that was synthesized and shown to impart similar reductions as a leading commercial dispersant but with a significantly different composition and molecular architecture.
Co-reporter:Kevin S. Silmore, Chetali Gupta, Newell R. Washburn
Journal of Colloid and Interface Science 2016 Volume 466() pp:91-100
Publication Date(Web):15 March 2016
DOI:10.1016/j.jcis.2015.11.042
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.
Co-reporter:Mohamed H. Ramadan, Nicole J. Sansone, Louisa M. Pendergast, Emily E. Friedrich and Newell R. Washburn
Analytical Methods 2016 vol. 8(Issue 6) pp:1222-1228
Publication Date(Web):26 Jan 2016
DOI:10.1039/C5AY03092G
Nonspecific protein adsorption can interfere with blood diagnostics, especially in point-of-care tests for which minimal sample processing is required. Here we report a non-fouling coating material for presenting capture antibodies in ELISA that significantly increased precision and accuracy compared to a commercial ELISA microplates in human plasma and model solutions containing plasma proteins. The coating was prepared by functionalizing the hydrophilic polysaccharide hyaluronic acid (HA) with a thermoresponsive polymer, poly(di(ethylene glycol)) methyl ether methacrylate (PMEO2MA). Previous studies demonstrated that these coatings were resistant to adsorption of major blood proteins, and we demonstrate that functionalization of the coatings with a monoclonal antibody against tumor necrosis factor-α (TNF-α) provided enhanced detection accuracy for this pro-inflammatory cytokine in ELISA. Three plasma-type solutions were explored in this work based either on buffer containing known concentrations of albumin, fibrinogen and immunoglobulin at sub-physiological and physiological concentrations, and non-diluted human plasma. In model solutions of plasma, even sub-physiological concentrations of plasma proteins resulted in a 20% overestimate of TNF-α concentration in the commercial ELISA kit but a 4% overestimate in HA-coated microwells. However, in human plasma, the commercial ELISA kit underestimated the analyte concentration by up to 95% while the HA-coated microwells did so by only 15% at an analyte concentration of 12.5 pg mL−1. The improvements in precision and accuracy provided by HA coatings suggests they could be used to enhance ELISA measurements in a broad range of complex biological media.
Co-reporter:Lisa R. Murray, Chetali Gupta, Newell R. Washburn, Kendra A. Erk
Journal of Colloid and Interface Science 2015 Volume 459() pp:107-114
Publication Date(Web):1 December 2015
DOI:10.1016/j.jcis.2015.07.037
•Lignopolymers have been synthesized as new superplasticizers for cement.•Lignopolymers were tested in model cementitious suspensions of magnesium oxide.•Comparisons with leading polycarboxylate ether (PCE) dispersant were performed.•At low concentrations, lignin-polyacrylamide was more effective than PCE.•Lignin-polyacrylamide was more effective at higher grafting densities than low.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 0.25 mg/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.
Co-reporter:Chetali Gupta, Madeline J. Sverdlove and Newell R. Washburn
Soft Matter 2015 vol. 11(Issue 13) pp:2691-2699
Publication Date(Web):11 Feb 2015
DOI:10.1039/C4SM02675F
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.
Co-reporter:Tejank Shah, Chetali Gupta, Rachel L. Ferebee, Michael R. Bockstaller, Newell R. Washburn
Polymer 2015 Volume 72() pp:406-412
Publication Date(Web):18 August 2015
DOI:10.1016/j.polymer.2015.04.073
Understanding of the governing parameters that control the interaction of bio-sourced fillers with synthetic polymer materials is a long-standing challenge for their exploitation as a platform for material engineering. For the case of graft-lignin embedded in poly (methyl methacrylate) (PMMA) it is demonstrated that tethering of polymeric chains with appropriate chain length to the surface of lignin-fillers dramatically increases the mechanical properties of PMMA/lignin composites, suggesting the PMMA grafts significantly enhanced filler–matrix interactions. Most metrics were maximized at 1% loading, with a 3-fold increase in yield stress, a 4-fold increase in tensile strength, and a 7-fold increase in toughness, with a combination of properties that compare favorably to high-performance engineering polymers and polymer nanocomposites based on inorganic nanoparticles. The versatility of the surface-initiated controlled radical polymerization used for polymer graft modification suggests that the approach should be broadly applicable to a wide range of commodity and engineering polymers.
Co-reporter:Emily E. Friedrich;Liang Tso Sun;Shanmugasundaram Natesan;David O. Zamora;Robert J. Christy
Journal of Biomedical Materials Research Part A 2014 Volume 102( Issue 5) pp:1527-1536
Publication Date(Web):
DOI:10.1002/jbm.a.34829
Abstract
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-1β 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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1527–1536, 2014.
Co-reporter:Mohamed H. Ramadan, Joseph E. Prata, Orsolya Karácsony, Gunnar Dunér, and Newell R. Washburn
Langmuir 2014 Volume 30(Issue 25) pp:7485-7495
Publication Date(Web):2017-2-22
DOI:10.1021/la500918p
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.
Co-reporter:Shayna L. Hilburg, Allison N. Elder, Hoyong Chung, Rachel L. Ferebee, Michael R. Bockstaller, Newell R. Washburn
Polymer 2014 Volume 55(Issue 4) pp:995-1003
Publication Date(Web):25 February 2014
DOI:10.1016/j.polymer.2013.12.070
Nanocomposites based on synthetic polymers grafted from kraft lignin with average particle size of 5 nm were synthesized using atom transfer radical polymerization (ATRP). Lignin macroinitiators were prepared, and polystyrene and poly(methyl methacrylate) were polymerized with target degree of polymerization of 450 resulting in materials having lignin mass fractions of 4.5%, 8.3%, and 22.1% for the poly(methyl methacrylate) samples and 3.2%, 7.1%, and 19.6% for the polystyrene samples. Tensile testing showed a decreased modulus but enhanced toughness of all nanocomposites compared to homopolymers, and the poly(methyl methacrylate)-grafted samples had nearly twice the ultimate elongation as the polystyrene grafts at high graft density. Both types of grafted nanocomposites had toughness values that were greater than 10-times that of the corresponding kraft-lignin/polymer blend system, indicating the potential of ATRP as the basis for the ‘one component’ composite approach towards more sustainable polymeric materials. Dynamical mechanical analysis was used to measure softening temperatures, and both the polystyrene-grafted and poly(methyl methacrylate)-grafted nanocomposites had a peak in the loss modulus that was higher than the corresponding homopolymer, consistent with strong polymer–lignin interactions. Lignin grafted with thermoplastic polymers could be an important material based on an inexpensive, renewable feedstock that offers unique mechanical properties compared with many other nanocomposites based on inorganic nanoparticles. Our results indicate that ATRP is well suited for preparing lignin-based thermoplastics and could be the basis for hybrid materials that make effective use of this important renewable resource.
Co-reporter:Chetali Gupta and Newell R. Washburn
Langmuir 2014 Volume 30(Issue 31) pp:9303-9312
Publication Date(Web):2017-2-22
DOI:10.1021/la501696y
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.
Co-reporter:Allison N. Elder, Susan K. Hannes, Sade F. Atoyebi, Newell R. Washburn
European Polymer Journal 2013 Volume 49(Issue 10) pp:2968-2975
Publication Date(Web):October 2013
DOI:10.1016/j.eurpolymj.2013.06.037
•Alternatives to PEGylation explored for conjugation to peptide against TNFα.•Higher molecular weight PEG conjugates had reduced binding kinetics.•Hyaluronic acid conjugates showed improved binding.•Strongest binding measured using 2 kDa PEG linker to hyaluronic acid.Conjugation of cytokine-neutralizing monoclonal antibodies (mAb) to hyaluronic acid (HA) having Mw of 1.6 MDa was previously shown to be an effective strategy for localized delivery to sites of inflammation. Despite the disparity in size of the mAb and HA, the mAb–HA conjugate was found bind tumor necrosis factor-α (TNFα) as strongly as the non-conjugated antibody, suggesting conjugation to this charged polysaccharide can provide an alternative to poly(ethylene glycol) (PEG) conjugation, which has been shown to reduce binding interactions for many proteins. To explore conjugation chemistries more systematically, we report a study on a model peptide inhibitor of tumor necrosis factor-α to investigate the effects of site-specific conjugation to HA and PEG. We compared the binding affinities of a variety of WP9QY peptide–polymer conjugates for TNFα in order to examine the effects of PEG molecular weight as well as the effects of PEG versus functionalized hyaluronic acid (HA) conjugation. The results indicate that the binding affinity of the PEG conjugates decreases in comparing PEG with mass 2 k, 10 k, and 30 k, which was attributed to PEG shrouding of the peptide, while conjugation to a 66 kDa HA chain preserved peptide binding affinity. We attribute this difference to the increased solubility of HA compared to PEG, potentially due to the carboxylic acid functional groups. In addition, the results demonstrate that conjugation to HA via a short PEG linker significantly enhances the association rate kon, which may reflect an increased peptide accessibility. By balancing both the advantages associated with the PEG conjugates and with the HA conjugates, the HA–PEG2k–WP9QY conjugate was able to improve the binding affinity of the peptide for TNFα by a factor of two. Optimization of polymer chemistry could be used to improve delivery of protein therapeutics for localized and systemic administration.Graphical abstract
Co-reporter:Hoyong Chung and Newell R. Washburn
ACS Applied Materials & Interfaces 2012 Volume 4(Issue 6) pp:2840
Publication Date(Web):May 10, 2012
DOI:10.1021/am300425x
Chemical modification strategies to improve the mechanical properties of lignin-based polyurethanes are presented. We hypothesized that treatment of lignin with Lewis acids would increase the concentration of hydroxyl groups available to react with diisocyanate monomers. Under the conditions used, hydrogen bromide-catalyzed modification resulted in a 28% increase in hydroxyl group content. Associated increases in hydrophilicity of solvent-cast thin films were also recorded as evidenced by decreases in water contact angle. Polyurethanes were then prepared by first preparing a prepolymer based on mixtures of toluene-2,4-diisocyanate (TDI) and unmodified or modified lignin, then polymerization was completed through addition of polyethylene glycol (PEG), resulting in mass ratios of TDI:lignin:PEG of 43:17:40 in the compositions investigated here. The mixture of TDI and unmodified lignin resulted in a lignin powder at the bottom of the liquid, suggesting it did not react directly with TDI. However, a homogeneous solution resulted when TDI and the hydrogen bromide-treated lignin were mixed, suggesting demethylation indeed increased reactivity and resulted in better integration of lignin into the urethane network. Significant improvements in mechanical properties of modified lignin polyurethanes were observed, with a 6.5-fold increase in modulus, which were attributed to better integration of the modified lignin into the covalent polymer network due to the higher concentration of hydroxyl groups. This research indicates that chemical modification strategies can lead to significant improvements in the properties of lignin-based polymeric materials using a higher fraction of an inexpensive lignin monomer from renewable resources and a lower fraction an expensive, petroleum-derived isocyanate monomer to achieve the required material properties.Keywords: Lewis acid; lignin; polyurethane; renewable resources;
Co-reporter:Newell R. Washburn
Journal of Biomedical Materials Research Part A 2011 Volume 96A( Issue 1) pp:58-65
Publication Date(Web):
DOI:10.1002/jbm.a.32943
Abstract
A model for incorporating an entrepreneurship module has been developed in an upper-division and graduate-level engineering elective on Polymeric Biomaterials (27-311/42-311/27-711/42-711) at Carnegie Mellon University. A combination of lectures, assignments, and a team-based project were used to provide students with a framework for applying their technical skills in the development of new technologies and a basic understanding of the issues related to translational research and technology commercialization. The specific approach to the project established in the course, which represented 20% of the students' grades, and the grading rubric for each of the milestones are described along with suggestions for generalizing this approach to different applications of biomaterials or other engineering electives. Incorporating this model of entrepreneurship into electives teaches students course content within the framework of technological innovation and many of the concepts and tools need to practice it. For students with situational or individual interest in the project, it would also serve to deepen their understanding of the traditional course components as well as provide a foundation for integrating technological innovation and lifelong learning. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010.
Co-reporter:Hoyong Chung, Paul Glass, Jewel M. Pothen, Metin Sitti, and Newell R. Washburn
Biomacromolecules 2011 Volume 12(Issue 2) pp:
Publication Date(Web):December 23, 2010
DOI:10.1021/bm101076e
We present a study on the effects of cross-linking on the adhesive properties of bio-inspired 3,4-dihydroxyphenylalanine (DOPA). DOPA has a unique catechol moiety found in adhesive proteins in marine organisms, such as mussels and polychaete, which results in strong adhesion in aquatic conditions. Incorporation of this functional group in synthetic polymers provides the basis for pressure-sensitive adhesives for use in a broad range of environments. A series of cross-linked DOPA-containing polymers were prepared by adding divinyl cross-linking agent ethylene glycol dimethacrylate (EGDMA) to monomer mixtures of dopamine methacrylamide (DMA) and 2-methoxyethyl acrylate (MEA). Samples were prepared using a solvent-free microwave-assisted polymerization reaction and compared to a similar series of cross-linked MEA materials. Cross-linking with EGDMA tunes the viscoelastic properties of the adhesive material and has the advantage of not reacting with the catechol group that is responsible for the excellent adhesive performance of this material. Adhesion strength was measured by uniaxial indentation tests, which indicated that 0.001 mol % of EGDMA-cross-linked copolymer showed the highest work of adhesion in dry conditions, but non-cross-linked DMA was the highest in wet conditions. The results suggest that there is an optimal cross-linking degree that displays the highest adhesion by balancing viscous and elastic behaviors of the polymer but this appears to depend on the conditions. This concentration of cross-linker is well below the theoretical percolation threshold, and we propose that subtle changes in polymer viscoelastic properties can result in significant improvements in adhesion of DOPA-based materials. The properties of lightly cross-linked poly(DMA-co-MEA) were investigated by measurement of the frequency dependence of the storage modulus (G′) and loss modulus (G′′). The frequency-dependence of G′ and magnitude of G′′ showed gradual decreases with the fraction of EGDMA. Loosely cross-linked DMA copolymers, containing 0% and 0.001 mol % of EGDMA-cross-linked copolymers, displayed rheological behavior appropriate for pressure-sensitive adhesives characterized by a higher G′ at high frequencies and lower G′ at low frequencies. Our results indicate that dimethacrylate cross-linking of DMA copolymers can be used to enhance the adhesive properties of this unique material.
Co-reporter:Liang Tso Sun, Sidi A. Bencherif, Thomas W. Gilbert, Michael T. Lotze, Newell R. Washburn
Acta Biomaterialia 2010 Volume 6(Issue 12) pp:4708-4715
Publication Date(Web):December 2010
DOI:10.1016/j.actbio.2010.06.029
Abstract
Constructs composed of cytokine-neutralizing antibodies conjugated to high-molecular-weight hyaluronic acid have been shown to be effective at controlling inflammatory responses in vivo. A critical question in the development of this new class of biomaterial is whether crosslinked conjugates have similar anti-inflammatory effects, which would open up a broad range of tissue engineering applications in which the material would have intrinsic inflammation-controlling function. To test this, high-molecular-weight hyaluronic acid was conjugated with monoclonal antibodies to the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in two forms of the material: viscous, non-crosslinked polymer–antibody conjugates and crosslinked, elastomeric polymer–antibody conjugates. The cytokine affinities of both constructs were validated using molecular characterization methods, and the biological activities were tested through subcutaneous implantation in Sprague–Dawley rats. In vitro, both forms of these constructs are capable of binding cytokines, but in vivo only the non-crosslinked polymer significantly reduces markers of acute inflammation compared to controls that lack the antibodies. We propose that these materials function by retarding cytokine diffusion, with the non-crosslinked polymers being capable of retarding the diffusion of cytokines in the extracellular matrix and preventing engagement with receptors. In contrast, crosslinked materials have long diffusion lengths into the gel compared with those between cells on the surface of the material, which may make them ineffective at sequestering pro-inflammatory cytokines on biologically relevant timescales. These results suggest an important design principle for preparing cytokine-regulating materials based on consideration of transport phenomena.
Co-reporter:Liang Tso Sun, Kyle S. Buchholz, Michael T. Lotze, and Newell R. Washburn
Molecular Pharmaceutics 2010 Volume 7(Issue 5) pp:1769-1777
Publication Date(Web):August 20, 2010
DOI:10.1021/mp100150z
Cytokine-neutralizing antibodies are used in treating a broad range of inflammatory conditions. We demonstrate that monoclonal antibodies against interleukin-1β and tumor necrosis factor-α were still active when conjugated to high molecular weight polysaccharides. These polysaccharides are hydrophilic, but their size makes them unable to circulate in the bloodstream when delivered to tissues, opening up the possibility of localized treatment of inflammatory conditions. To explore this new class of protein−polysaccharide conjugates, we covalently modified interleukin-1β and tumor necrosis factor-α monoclonal antibodies with high molecular weight hyaluronic acid and carboxymethylcellulose. Rigorous purification using dialysis with a 300 kDa-cutoff membrane removed unconjugated monoclonal antibodies. We characterized the composition of the constructs and demonstrated using molecular binding affinity measurements and cell assays that the conjugates were capable of binding proinflammatory cytokines. The binding affinities of both the unconjugated antibodies for their cytokines were measured to be approximately 120 pM. While all conjugates had pM-level binding constants, they ranged from 40 pM for the hyaluronic acid−(anti-interleukin-1β) conjugate to 412 pM for the carboxymethylcellulose−(anti-interleukin-1β) conjugate. Interestingly, the dissociation time constants varied more than the association time constants, suggesting that conjugation to a high molecular weight polysaccharide did not interfere with the formation of the antibody−cytokine complex but could stabilize or destabilize it once formed. Conjugation of cytokine-neutralizing antibodies to high molecular weight polymers represents a novel method of delivering anticytokine therapeutics that may avoid many of the complications associated with systemic delivery.Keywords: Antibody; cytokine; inflammation; polysaccharide;
Co-reporter:Joseph E. Prata, Tiffany A. Barth, Sidi A. Bencherif and Newell R. Washburn
Biomacromolecules 2010 Volume 11(Issue 3) pp:
Publication Date(Web):February 11, 2010
DOI:10.1021/bm901373x
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Co-reporter:Sidi A. Bencherif, Abiraman Srinivasan, Jeffrey A. Sheehan, Lynn M. Walker, Chakicherla Gayathri, Roberto Gil, Jeffrey O. Hollinger, Krzysztof Matyjaszewski, Newell R. Washburn
Acta Biomaterialia 2009 Volume 5(Issue 6) pp:1872-1883
Publication Date(Web):July 2009
DOI:10.1016/j.actbio.2009.02.030
Abstract
A series of resorbable poly(ethylene glycol)-co-poly(glycolic acid) (PEG-co-PGA, 4KG5) macromonomers have been synthesized with the chemistries from three different photopolymerizable end-groups (acrylates, methacrylates and urethane methacrylates). The aim of the study is to examine the effects of the chemistry of the cross-linker group on the properties of photocross-linked hydrogels. 4KG5 hydrogels were prepared by photopolymerization with high vinyl group conversion as confirmed by 1H nuclear magnetic resonance spectrometry using a 1D diffusion-ordered spectrometry pulse sequence. Our study reveals that the nature of end-groups in a moderately amphiphilic polymer can adjust the distribution and size of the micellar configuration in water, leading to changes in the macroscopic structure of hydrogels. By varying the chemistry of the cross-linker group (diacrylates (DA), dimethacrylates (DM) and urethane dimethacrylates (UDM)), we determined that the hydrophobicity of a single core polymer consisting of poly(glycolic acid) could be fine-tuned, leading to significant variations in the mechanical, swelling and degradation properties of the gels. In addition, the effects of cross-linker chemistry on cytotoxicity and proliferation were examined. Cytotoxicity assays showed that the three types of hydrogels (4KG5 DA, DM and UDM) were biocompatible and the introduction of RGD ligand enhanced cell adhesion. However, differences in gel properties and stability differentially affected the spreading and proliferation of myoblast C2C12 cells.
Co-reporter:Sidi A. Bencherif;Jeffrey A. Sheehan;Jeffrey O. Hollinger;Lynn M. Walker;Krzysztof Matyjaszewski
Journal of Biomedical Materials Research Part A 2009 Volume 90A( Issue 1) pp:142-153
Publication Date(Web):
DOI:10.1002/jbm.a.32069
Abstract
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(glycolic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydrogels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoencapsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Co-reporter:Sidi A. Bencherif, Haifeng Gao, Abiraman Srinivasan, Daniel J. Siegwart, Jeffrey O. Hollinger, Newell R. Washburn and Krzysztof Matyjaszewski
Biomacromolecules 2009 Volume 10(Issue 7) pp:
Publication Date(Web):June 11, 2009
DOI:10.1021/bm900213u
This study presents the synthesis and evaluation of cell adhesive poly(ethylene oxide) (PEO) star polymers for potential biomedical applications. Star polymers with a size of approximately 20 nm and with relatively low polydispersities (Mw/Mn ≤ 1.6), containing GRGDS (Gly-Arg-Gly-Asp-Ser) segments, were prepared by atom transfer radical copolymerization of PEO methyl ether methacrylate macromonomer (MM), telechelic GRGDS-PEO-acrylate MM, and ethylene glycol dimethacrylate (EGDMA). Results from 1H NMR spectroscopy confirmed the covalent incorporation of the peptide into the star periphery. In vitro cytotoxicity experiments showed star polymers to be cytocompatible (≥95% cell viability) and GRGDS-star hybrid hydrogels supported the attachment of MC3T3.E1 (subclone 4) cells. Hybrid hydrogels were prepared by free radical photopolymerization based on 10% (wt/v) PEO dimethacrylates Mn = 4000 g/mol with 1% (wt/v) GRGDS-star polymers having different peptide content. Cell adhesiveness was also determined from thin film coatings prepared with GRGDS-containing star polymers on nonadherent plastic plates. After 24 h incubation, phase contrast microscopy and scanning electron microscopy (SEM) images showed uniform cell adhesion and distribution over the film containing cell-adhesive star polymers. These results confirm that incorporation of RGD ligand-binding motifs into PEO-based star polymers is required to influence substrate−cell interactions.
Co-reporter:James A. Cooper Jr., Wan-Ju Li, LeeAnn O. Bailey, Steve D. Hudson, Sheng Lin-Gibson, Kristi S. Anseth, Rocky S. Tuan, Newell R. Washburn
Acta Biomaterialia 2007 Volume 3(Issue 1) pp:13-21
Publication Date(Web):January 2007
DOI:10.1016/j.actbio.2006.08.010
Abstract
We have developed a bioreactor-based millifluidic technique that allows for dynamic culture conditions and measurement of the fluid flow impinging upon a three-dimensional tissue engineering scaffold. Chondrocytes in scaffolds have been shown to require mechanical stimulation to produce an extracellular matrix that resembles native cartilage. This study investigates the effect of pulsatile flow on chondrocyte response in a model poly(ethylene glycol) dimethacrylate hydrogel. Bovine chondrocytes were encapsulated in the hydrogel and cultured for 7, 14 and 21 days at pulsatile flow frequencies of 0.5 Hz (15 ml/min) and 1.5 Hz (17 ml/min). The scaffolds cultured under dynamic conditions were compared to those cultured under static (non-flow) conditions. Quantitative real-time reverse transcription polymerase chain reaction was used to quantify collagen type I, collagen type II and aggrecan gene copy numbers as markers for chondrocyte phenotypic expression. Histological sections stained with hematoxylin & eosin, and Alcian blue confirmed chondrocyte morphology and matrix formation. Interestingly, regulation of the collagen type II gene was particularly sensitive to the flow conditions. The understanding of the cell response to encapsulation and flow could be used to identify the appropriate culture conditions necessary to design and develop hydrogel carriers to promote the formation of extracellular matrix as well as to further our knowledge of chondrocyte mechanobiology.
Co-reporter:Emily E. Friedrich, Newell R. Washburn
Biomaterials (January 2017) Volume 114() pp:10-22
Publication Date(Web):January 2017
DOI:10.1016/j.biomaterials.2016.11.003
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.
Co-reporter:Emily E. Friedrich, Newell R. Washburn
Biomaterials (January 2017) Volume 114() pp:10-22
Publication Date(Web):January 2017
DOI:10.1016/j.biomaterials.2016.11.003
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