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.

Hydrogel models of metastasis traditionally focus on the invasion of cancer cells; however, other cells in the tumor microenvironment that are associated with metastasis also have the ability to migrate. Macrophage phenotype plays a key role in the tumor microenvironment, yet understanding their migration within tunable 3D in vitro models has been limited. To gain a greater understanding of macrophage invasive behavior, stable and transparent oxime‐crosslinked cryogels comprised of click‐crosslinked gelatin‐oxyamine and hyaluronan‐aldehyde (GELox‐HAa) are synthesized. Fibronectin‐derived, oxyamine‐modified PHSRN‐RGDSP peptides are incorporated to further mimic the tumor extracellular matrix without impacting cryogel mechanics. It is found that primary human macrophages migrate to a greater depth in cryogels with greater porosity and pore size. To better understand the mechanism of migration, cells are treated with either inhibitors of matrix metalloproteinases (MMPs) or rho‐associated protein kinase (ROCK) and a predominantly MMP‐mediated mechanism of invasion is found. Macrophage polarization studies reveal that anti‐inflammatory, interleukin‐4/13 (IL4/IL13)‐treated macrophages migrate through cryogels to a greater extent than pro‐inflammatory, interferon‐gamma/lipopolysaccharide (IFNγ/LPS)‐treated cells. Interestingly, polarized macrophages move through cryogels using a combination of amoeboid and mesenchymal migration. These findings of macrophage invasion in this cryogel platform set the stage for their further study in a biomimetic tumor microenvironment.

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.

No abstract

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.

No abstract