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We report the fabrication of a tubular polydimethylsiloxane (PDMS) platform containing arrays of small pores on the wall for modeling blood vessels in vitro. The thin PDMS tubes are produced following our previously reported templating approach, while the pores are subsequently generated using focused laser ablation. As such, when these perforated PDMS tube are populated with a monolayer of endothelial cells on the interior surfaces and embedded within an extracellular matrix (ECM)-like environment, the endothelial cells can sprout out from the tubes into the surrounding matrix through the open pores. When a pair of perforated PDMS tubes are placed in parallel in the matrix, formation of an interconnected network of microvasculature or larger vessels occurs, which is dependent on the flow dynamics within the PDMS tubes. Moreover, when co-cultured with tumor spheroids, the onset of tumor angiogenesis is observed. Our perforated and endothelialized PDMS tubes are believed to enable convenient vascular modeling in vitro and will likely contribute to improved biological studies as well as therapeutic screening.

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The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.

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Two new series of pyrazolobenzothiazine-based carbothioamides (3a-o and 4a-o) were synthesized using saccharin as the starting material. The synthesized derivatives were investigated for their ability to inhibit monoamine oxidases (MAO). Compound 3b was found to be a very potent MAO-A inhibitor with an IC50 value of 0.003 ± 0.0007 µM, while compound 4d was the most effective inhibitor of MAO-B having an IC50 value of 0.02 ± 0.001 µM. Molecular docking studies were performed to identify the probable binding modes in the active site of the monoamine oxidase enzymes. The synthetic and computational investigations in the current work suggested that these newly identified inhibitors may serve as a powerful starting point for the exploration and optimization of potential therapeutic agents targeting Parkinson's disease.

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The multifactorial nature of Parkinson's disease necessitates the development of new chemical entities with inherent ability to address key pathogenic processes. To this end, two series of new symmetrical 1,2- and 1,4-bis(2-aroyl/alkoylimino-5-(2-methoxy-2-oxoethylidene)-4-oxo-thiazolidin-3-yl)benzene derivatives (3a-g and 5a-e) were synthesized in good yields by the cyclization of 1,2- and 1,4-bis(N'-substituted thioureido)benzene intermediates with dimethyl acetylenedicarboxylate (DMAD) in methanol at ambient temperature. The bis-iminothiazolidinone compounds were investigated in vitro for their inhibition of monoamine oxidase (MAO-A & MAO-B) enzymes with the aim to identify new and distinct pharmacophores for the treatment of neurodegenerative disorders like Parkinson's disease. Most of the designed compounds exhibited good inhibitory efficacy against monoamine oxidases. Compound 5a was identified as the most potent inhibitor of MAO-A depicting an IC50 value of 0.001µM, a 4-fold stronger inhibitory strength compared to standard inhibitor (clorgyline: IC50=0.0045µM). Molecular docking studies provided insights into enzyme-inhibitor interactions and a rationale for the observed inhibition towards monoamine oxidases.

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The development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled extrusion of bioinks from a single printhead consisting of bundled capillaries synergized with programmed movement of the motorized stage.

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Conventional blood vessel-on-a-chip models are typically based on microchannel-like structures enclosed within bulk elastomers such as polydimethylsiloxane (PDMS). However, these bulk vascular models largely function as individual platforms and exhibit limited flexibility particularly when used in conjunction with other organ modules. Oftentimes, lengthy connectors and/or tubes are still needed to interface multiple chips, resulting in a large waste volume counterintuitive to the miniaturized nature of organs-on-chips. In this work, we report the development of a novel form of a vascular module based on PDMS hollow tubes, which closely emulates the morphology and properties of human blood vessels to integrate multiple organs-on-chips. Specifically, we present two templating strategies to fabricate hollow PDMS tubes with adjustable diameters and wall thicknesses, where metal rods or airflow were employed as the inner templates, while plastic tubes were used as the outer template. The PDMS tubes could then be functionalized by human umbilical vein endothelial cells (HUVECs) in their interior surfaces to further construct elastomeric biomimetic blood vessels. The endothelium developed biofunctionality as demonstrated by the expression of an endothelial biomarker (CD31) as well as dose-dependent responses in the secretion of von Willebrand factor and nitric oxide upon treatment with pharmaceutical compounds. We believe that with their clear advantages including high optical transparency, gas permeability, and tunable elasticity matching those of native blood vessels, these free-form PDMS vascular modules can supplement bulk vascular organoids and likely replace inert plastic tubes in integrating multiple organoids into a single microfluidic circuitry.

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Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a-3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 µM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 µM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones.

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