Viscoelastic Supramolecular Hyaluronan-Peptide Cross-Linked Hydrogels.

Viscoelasticity plays a key role in hydrogel design. We designed a physically cross-linked hydrogel with tunable viscoelasticity, comprising supramolecular-assembled peptides coupled to hyaluronan (HA), a native extracellular matrix component. We then explored the structural and molecular mechanisms underlying the mechanical properties of a series of these HA-peptide hydrogels. By modifying the peptide sequence, we modulated both long- and short-time stress relaxation rates as a way to target viscoelasticity with limited impact on stiffness, leading to gels that relax up to 60% of stress in 10 min. Gels with the highest viscoelasticity exhibited large mesh sizes and ß-sheet secondary structures. The stiffness of the gel correlated with hydrogen bonding between the peptide chains. These gels are cytocompatible: highly viscoelastic gels that mimic the native skin microenvironment promote dermal fibroblast cell spreading. Moreover, HA-peptide gels enabled cell encapsulation, as shown with primary human T cells. Overall, these physically-cross-linked hydrogels enable tunable viscoelasticity that can be used to modulate cell morphology.

Inverse Electron-Demand Diels-Alder Methylcellulose Hydrogels Enable the Co-delivery of Chondroitinase ABC and Neural Progenitor Cells.

A hydrogel that can deliver both proteins and cells enables the local microenvironment of transplanted cells to be manipulated with a single injection. Toward this goal, we designed a hydrogel suitable for the co-delivery of neural stem cells and chondroitinase ABC (ChABC), a potent enzyme that degrades the glial scar that forms after central nervous system (CNS) injury. We leveraged the inverse electron-demand Diels-Alder reaction between norbornene and methylphenyltetrazine to form rapidly gelling (<15 min) crosslinked methylcellulose (MC) hydrogels at physiological temperature and pH, with Young's modulus similar to that of brain tissue (1-3 kPa), and degradable, disulfide-containing crosslinkers. To achieve tunable, affinity-controlled release of a ChABC-Src homology 3 (SH3) fusion protein, we immobilized norbornene-functionalized SH3-binding peptides onto MC-methylphenyltetrazine and observed release of bioactive ChABC-SH3 over 4 days. We confirmed cytocompatibility by evaluating neural progenitor cell survival and proliferation. The combined encapsulation of neural stem cells and chondroitinase ABC from one hydrogel lays the framework for future in vivo studies to treat CNS injuries.

Role of bioaerosol in virus transmission and material-based countermeasures.

Respiratory pathogens transmit primarily through particles such as droplets and aerosols. Although often overlooked, the resuspension of settled droplets is also a key facilitator of disease transmission. In this review, we discuss the three main mechanisms of aerosol generation: direct generation such as coughing and sneezing, indirect generation such as medical procedures, and resuspension of settled droplets and aerosols. The size of particles and environmental factors influence their airborne lifetime and ability to cause infection. Specifically, humidity and temperature are key factors controlling the evaporation of suspended droplets, consequently affecting the duration in which particles remain airborne. We also suggest material-based approaches for effective prevention of disease transmission. These approaches include electrostatically charged virucidal agents and surface coatings, which have been shown to be highly effective in deactivating and reducing resuspension of pathogen-laden aerosols.

Sequence-Controlled Polyurethane Block Copolymer Displays Differentiated Immunoglobulin-G Adsorption That Influences Human Monocyte Adhesion and Activity.

The ability to specify an adsorbed protein layer through the polymer chemistry design of immunomodulatory biomaterials is important when considering a desired immune response, such as reducing pro-inflammatory activity. Limited work has been undertaken to elucidate the role of monomer sequence in this process, when copolymeric systems are involved. In this study, we demonstrate the advantage of an alternating radical copolymerization strategy as opposed to a random statistical copolymerization to order monomers in the synthesis of degradable polar-hydrophobic-ionic polyurethanes (D-PHI), biomaterials originally designed to reduce inflammatory monocyte activation. A monomer system consisting of a vinyl-terminated polyurethane cross-linker, maleic acid (MA), and ethyl vinyl ether (EVE), not only generated a diverse chemical environment of polar, hydrophobic, and ionic functional groups, but also formed a charge transfer complex (CTC) reactive to alternating polymerizations. Conversion of MA and EVE occurred in a constant proportion regardless of monomer availability, a phenomenon not observed in conventional D-PHI formulations. For feeds with unequal molar quantities of MA and EVE, the final conversion was limited and proportional to the limiting reagent, leading to an overall higher polyurethane cross-linker content. The presence of a reactive CTC was also found to limit the monomer conversion. Compared to a D-PHI with random monomer arrangement using methacrylic acid (MAA) and methyl methacrylate (MMA), a reduction in Fab region exposure from adsorbed immunoglobulin G and a reduction in average adherent monocyte activity were found in the sequence-controlled version. These results represent the first example of using an alternating copolymerization approach to generate regularly defined polymer chemistries in radical chain-growth biomaterials for achieving immunomodulation, and highlight the importance of considering sequence control as a design strategy for future immunomodulatory biomaterial development.

Toxin-Mediated siRNA Delivery.

AB toxins with built-in cell targeting and endosomal escape mechanisms are attractive intracellular delivery vehicles. However, their compatibility with nucleic-acid-based therapeutics is not fully explored. Arnold et al. demonstrated the first functional siRNA delivery by diphtheria toxin (DT) in vitro, marking an important step in expanding the utility of AB toxins for nucleic acid delivery.