Recent advent of additive manufacturing potentiates the fabrication of microchannels, albeit with limitations in resolution of printed structures, freedom of geometry, and choice of printable materials. Herein, a method is developed by sacrificial molding to fabricate microchannels in various polymer matrices and geometries. This method allows for rapid fabrication of 3D microchannels and channels harboring intricate in‐channel features. The method uses commercially available fused deposition modeling 3D printer and filament made of polyvinyl alcohol (PVA). Mechanically stable molds are fabricated for 3D microchannels that can be completely removed in water. Importantly, the PVA mold is stable and resilient in hydrogels despite being hygroscopic. Perfusion channels are fabricated in biocompatible substrates such as gelatin and poly(ethylene glycol) diacrylate. Fabrication of the network of 3D multilayer microchannels is demonstrated by preassembling sacrificial molds from modular pieces of molds. Intricate staggered‐herringbones grooves (SHGs) are also fabricated within microchannels to produce micromixers. The versatility and resilience of the method developed here is advantageous for biological and chemical applications that require 3D configurations of microchannels in various matrices, which would not be compatible with fabrication by direct 3D printing and softlithography.
Class I histone deacetylases (HDACs) are highly expressed and/or upregulated in hepatocellular carcinoma (HCC) and are associated with aggressiveness, spread, and increased mortality of HCC. Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. A series of purine or 5H-pyrrolo[3,2-d]pyrimidine based hydroxamates were designed and developed as multitarget drugs to modulate both HDACs and the PI3K/Akt/mTOR pathway. Among 39 cell lines screened, the molecules (e.g., 20e, 20f, and 20q) were the most selective against leukemia, lymphoma, and HCC cells; they also demonstrated target modulation in cancer cell lines and in mice bearing MV4-11 and HepG2 tumors. Compound 20f in particular showed significant single agent oral efficacy in hypervascular liver cancer models (e.g., HepG2, HuH-7, and Hep3B) and was well-tolerated. These encouraging results, along with its favorable target profile and tissue distribution, warrant further development of 20f.
A perfusable and stretchable gelatin-based microfluidic system that can apply both simultaneous fluidic shear stress and stretch stress to in vitro endothelial 3D tissues is presented.
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