Branched polyethylene glycol (four arms, MW =
15 000) having a cinnamylidene acetyl moiety as a
pendant group was synthesized by an esterification reaction between
polyethylene glycol and cinnamylidene acetyl
chloride. The photosensitive polymer was irradiated with a 450 W
medium pressure Hg lamp (λ > 300 nm) from
5 min to 3 h to produce polyethylene glycol hydrogels. These gels
were swollen in water and showed characteristic
properties of a hydrogel. The degree of swelling was controlled by
the content of cinnamylidene acetyl moiety in
the polymer and the time of ultraviolet irradiation. A reduced
degree of substitution resulted in increased swellability
of the synthesized hydrogel. The photoscission of the gel, which
was monitored by its UV spectrum, was performed
by irradiating the hydrogel with a 150 W Xenon lamp at 254 nm using a
bandpass filter. The biocompatibility of
the synthesized gel was also determined. The antithrombogenic
behavior (99.6% reduction in platelet deposition) of
the synthesized b-PEG-CA hydrogel was demonstrated by measuring
platelet adhesion onto coverslips which had
been coated with PMMA with a second coating film of b-PEG-CA
hydrogel.
Research in low Earth orbit (LEO) has become more accessible. The 2020 Biomanufacturing in Space Symposium reviewed spacebased regenerative medicine research and discussed leveraging LEO to advance biomanufacturing for regenerative medicine applications. The symposium identified areas where financial investments could stimulate advancements overcoming technical barriers. Opportunities in disease modeling, stem-cell-derived products, and biofabrication were highlighted. The symposium will initiate a roadmap to a sustainable market for regenerative medicine biomanufacturing in space. This perspective summarizes the 2020 Biomanufacturing in Space Symposium, highlights key biomanufacturing opportunities in LEO, and lays the framework for a roadmap to regenerative medicine biomanufacturing in space.
Endothelial cells (EC) of angiogenic tumor vasculature are characterized by altered expression of molecular markers on their surface. Numerous peptides have been identified that specifically bind tumor angiogenic endothelium, including the tripeptide arginine-arginine-leucine (RRL). We hypothesized that ultrasound contrast microbubbles (MB) targeted via linkage with RRL would specifically adhere to tumor angiogenic endothelium versus normal myocardium, and that this selective adhesion could be detected ultrasonically. Microbubbles were conjugated to cyclic peptides containing either RRL (RRL-MB) or a glycine control sequence (control-MB). As measured in a parallel plate flow chamber, in vitro adhesion of RRL-MBs was three times greater to cultured tumor–derived ECs than to normal ECs (P < 0.01), demonstrating selective binding of RRL-MBs to tumor endothelium. Mice bearing s.c. Clone C or PC3 tumors were given i.v. injections of fluorescent RRL to show in vivo localization to tumor vasculature or were ultrasonically imaged following i.v. injections of targeted contrast MBs. Ultrasound images showed strong RRL-MB contrast enhancement within the tumors but not the control tissue myocardium. Control-MBs caused minimal enhancement in either tissue. Quantitative acoustic videointensity was significantly greater for the tumors than the hearts (5 ± 1 versus 0.5 ± 1 intensity units; P = 0.001). These data show that ultrasound contrast MBs targeted to tumor vasculature via RRL preferentially adhere to tumor versus normal vasculature and that this selective adherence can be detected with ultrasound. Targeted microbubbles may thus offer a noninvasive contrast-enhanced ultrasound imaging technique for the functional imaging of tumor neovascularization, and may have further implications for therapeutic tumor targeting.
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