Additive manufacturing has the potential to change medicine, but clinical applications are limited by a lack of resorbable, printable materials. Herein, we report the first synthesis of polylactone ...and poly(propylene fumarate) (PPF) block copolymers with well-defined molecular masses and molecular mass distributions using sequential, ring-opening polymerization and ring-opening copolymerization methods. These new copolymers represent a diverse platform of resorbable printable materials. Furthermore, these polymers open a previously unexplored range of accessible properties among stereolithographically printable materials, which we demonstrate by printing a polymer with a molecular mass nearly 4 times that of the largest PPF homopolymer previously printed. To further demonstrate the potential of these materials in regenerative medicine, we report the postprinting “click” functionalization of the material using a copper-mediated azide–alkyne cycloaddition.
We present a molecular dynamics study of the binding process of peptide A3 (AYSSGAPPMPPF) and other similar peptides onto gold surfaces, and identify the functions of many amino acids. Our results ...provide a clear picture of the separate regimes present in the binding process: diffusion, anchoring, crawling and binding. Moreover, we explored the roles of individual residues. We found that tyrosine, methionine, and phenylalanine are strong binding residues; serine serves as an effective anchoring residue; proline acts as a dynamic anchoring point, while glycine and alanine give flexibility to the peptide backbone. We then show that our findings apply to unrelated phage-derived sequences that have been reported recently to facilitate AuNP synthesis. This new knowledge may aid in the design of new peptides for the synthesis of gold nanostructures with novel morphologies.
New methods to introduce and control polymer network crosslinking and improve mechanical properties of the resulting materials have been investigated extensively. Common methods to enhance the ...mechanical properties of elastomers include “vulcanization” by which polymer chains are covalently crosslinked. In this work, we outline a new method to crosslink well-defined, synthetic elastomers using “click” reactions. Specifically, 2-butyne-1,4-diyl dipropiolate which possesses both external and internal alkynes, was synthesized as a functional monomer and copolymerized with dithiols to yield a series of elastomeric materials possessing variations in cis stereochemistry. Notably, the glass-transition temperature and mechanical properties of the resulting copolymers can be tuned by changing the stoichiometry between 2-butyne-1,4-diyl dipropiolate and 1,3-propane diyl dipropiolate. The alkyne functionalities within the backbone allow for post-polymerization interchain crosslinking to form polymer networks using a ruthenium-catalyzed azide–alkyne cycloaddition. Hysteresis tests have shown that tensile modulus and recovery can be controlled by the density of the crosslinking within the network.
Polymer thin films are often used in transdermal patches as a method of continuous drug administration for patients with chronic illness. Understanding the drug segregation and distribution within ...these films is important for monitoring proper drug release over time. Surface-layer matrix-assisted laser desorption/ionization mass spectrometry imaging (SL-MALDI-MSI) is a unique analytical technique that provides an optical representation of chemical compositions that exist at the surface of polymeric materials. Solvent-free sublimation is employed for application of matrix to the sample surface, so that only molecules in direct contact with the matrix layer are detected. Here, these methodologies are utilized to visualize variations in drug concentration at both the air and substrate interface in pharmaceutical-loaded polymer films.
Efficient, reproducible, and precise methodologies for fabricating tissue engineering (TE) scaffolds using three-dimensional (3D) printing techniques are evaluated. Fusion deposition modeling, laser ...sintering, and photo printing each have limitations, including the materials that can be used with each printing system. However, new and promising resorbable materials are surfacing as alternatives to previously studied resorbable TE materials for 3D printing. One such resorbable polymer is poly(propylene fumarate) (PPF), which can be printed using photocross-linking 3D printing. The ability to print new materials opens up TE to a wide range of possibilities not previously available. The ability to control precise geometries, porosity, degradation, and functionalities present on 3D printable polymers such as PPF shows a new layer of complexity available for the design and fabrication of TE scaffolds.
The adhesive nature of mussels arises from the catechol moiety in the 3,4-dihydroxyphenylalanine (DOPA) amino acid, one of the many proteins that contribute to the unique adhesion properties of ...mussels. Inspired by these properties, many biomimetic adhesives have been developed over the past few years in an attempt to replace adhesives such as fibrin, cyanoacrylate, and epoxy glues. In the present work, we synthesized ethanol soluble but water insoluble catechol functionalized poly(ester urea) random copolymers that help facilitate delivery and adhesion in wet environments. Poly(propylene glycol) units incorporated into the polymer backbone impart ethanol solubility to these polymers, making them clinically relevant. A catechol to cross-linker ratio of 10:1 with a curing time of 4 h exceeded the performance of commercial fibrin glue (4.8 ± 1.4 kPa) with adhesion strength of 10.6 ± 2.1 kPa. These adhesion strengths are significant with the consideration that the adhesion studies were performed under wet conditions.
Immobilizing zwitterionic molecules on material surfaces has been a promising strategy for creating antifouling surfaces. Herein, we show the ability to surface derivatize an ...allyl-ether-functionalized thermoplastic polyurethane (TPU) with a zwitterionic thiol in a radically induced thiol–ene reaction. The thermoplastic polyurethane was synthesized to have an allyl-ether side functionality using a modified chain extender molecule. The zwitterion surface functionalization was achieved via thiol–ene reaction in aqueous conditions. The presence of chemically tethered zwitterion moieties on the TPU surface was confirmed using X-ray photoelectron spectroscopy (XPS). Protein adsorption experiments via quartz crystal microbalance (QCM) show reduced fibrinogen attachment for the zwitterion-derivatized TPU when compared to its nonfunctionalized controls. The Zwitterion-TPU also showed a log scale reduction in bacterial adherence. For Pseudomonas aeruginosa and Staphylococcus epidermidis, the Zwitterion-TPU resulted in around a 40 and 50% lower bacterial biomass accumulation, respectively, over the time scale of the experiment. The fibroblast cell viability of TPU remained unaffected by functionalization with zwitterion thiol. The results from our model experiments suggest that a zwitterion-modified TPU is a promising candidate for antifouling catheters.
Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have ...been ongoing for decades. However, materials that possess the mechanical, chemical, and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.
Degradation of Gram-positive bacterial cell wall peptidoglycan in macrophage and dendritic cell phagosomes leads to activation of the NLRP3 inflammasome, a cytosolic complex that regulates processing ...and secretion of interleukin (IL)-1β and IL-18. While many inflammatory responses to peptidoglycan are mediated by detection of its muramyl dipeptide component in the cytosol by NOD2, we report here that NLRP3 inflammasome activation is caused by release of N-acetylglucosamine that is detected in the cytosol by the glycolytic enzyme hexokinase. Inhibition of hexokinase by N-acetylglucosamine causes its dissociation from mitochondria outer membranes, and we found that this is sufficient to activate the NLRP3 inflammasome. In addition, we observed that glycolytic inhibitors and metabolic conditions affecting hexokinase function and localization induce inflammasome activation. While previous studies have demonstrated that signaling by pattern recognition receptors can regulate metabolic processes, this study shows that a metabolic enzyme can act as a pattern recognition receptor.
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•Peptidoglycan-derived N-acetylglucosamine activates the NLRP3 inflammasome•N-acetylglucosamine in the cytosol is detected by hexokinase•Hexokinase release from mitochondrial outer membranes triggers NLRP3 activation•Metabolic conditions affecting hexokinase activity trigger inflammasome formation
The metabolic enzyme hexokinase unexpectedly acts as a pattern recognition receptor that recognizes bacterial peptidoglycan and triggers activation of inflammasomes.
A zinc/acetic acid-mediated Clemmensen reduction coupled with sonication affords a time-dependent regio-random reduction of degradable poly(propylene maleate) oligomers to poly(propylene ...fumarate-co-propylene succinate) co-polymers. Characterization by 1H and 13C NMR spectroscopy, size exclusion chromatography, UV–vis spectroscopy, differential scanning calorimetry, and rheology demonstrates that the solvent used for the reduction can be tuned to afford copolymers with random succinate content not previously accessible without chain scission. These copolymers show lower molar extinction coefficients and reduced viscosities compared to previous unsaturated analogues. Together these features afford faster and improved 3D-printability using stereolithographic conditions. The variation in network properties, succinate stoichiometry, and polymer mass fraction allow the mechanical properties of the photochemically printed structures to be tuned widely.
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