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.
Current environmental challenges and the shrinking fossil‐fuel feedstock are important criteria for the next generation of polymer materials. In this context, we present a fully bio‐based material, which shows promise as thermoplastic elastomer (TPE). Due to the use of β‐farnesene and L‐lactide as monomers, bio‐based feedstocks, namely sugar cane and corn can be used. A bifunctional initiator for the carbanionic polymerization was employed, to permit an efficient synthesis of ABA‐type block structures. In addition, the “green” solvent MTBE (methyl tert‐butyl ether) was used. This afforded low dispersity (Đ = 1.07 to 1.10) and telechelic polyfarnesene macroinitiators. These were employed for lactide polymerization to obtain H‐shaped triblock copolymers. TEM and SAXS revealed clearly phase‐separated morphologies and tensile tests revealed elastic mechanical properties. The materials featured two glass transition temperatures, at ‐ 66 °C and 51 °C as well as gyroid or cylindrical morphologies, resulting in soft elastic materials at room temperature.
In the field of carbanionic polymerization bifunctional initiators permit the synthesis of complex triblock copolymer structures. Using 1,3 bis(1-phenylethenyl) benzene (PEB), isoprene was polymerized in cyclohexane, yielding high content of...
Current environmental challenges and the shrinking fossil‐fuel feedstock are important criteria for the next generation of polymer materials. In this context, we present a fully bio‐based material, which shows promise as thermoplastic elastomer (TPE). Due to the use of β‐farnesene and L‐lactide as monomers, bio‐based feedstocks, namely sugar cane and corn can be used. A bifunctional initiator for the carbanionic polymerization was employed, to permit an efficient synthesis of ABA‐type block structures. In addition, the “green” solvent MTBE (methyl tert‐butyl ether) was used. This afforded low dispersity (Đ = 1.07 to 1.10) and telechelic polyfarnesene macroinitiators. These were employed for lactide polymerization to obtain H‐shaped triblock copolymers. TEM and SAXS revealed clearly phase‐separated morphologies and tensile tests revealed elastic mechanical properties. The materials featured two glass transition temperatures, at ‐ 66 °C and 51 °C as well as gyroid or cylindrical morphologies, resulting in soft elastic materials at room temperature.
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