3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation-based microtomography

Cirrhosis describes the development of excess fibrous tissue around regenerative nodules in response to chronic liver injury and usually leads to irreversible organ damage and end-stage liver disease. During the development of cirrhosis, the formation of collagenous scar tissue is paralleled by a reorganization and remodeling of the hepatic vascular system. To date, macrovascular remodeling in various cirrhosis models has been examined using three-dimensional (3D) imaging modalities, while microvascular changes have been studied mainly by two-dimensional (2D) light microscopic and electron microscopic imaging. Here, we report on the application of high-resolution 3D synchrotron radiation-based microtomography (SRμCT) for the study of the sinusoidal and capillary blood vessel system in three murine models of advanced parenchymal and biliary hepatic fibrosis. SRμCT facilitates the characterization of microvascular architecture and identifies features of intussusceptive angiogenesis in progressive liver fibrosis in a non-destructive 3D manner.

Fabrication of Microneedle Mimicking Mosquito Proboscis Using Nanoscale 3D Laser Lithography System

A mosquito’s proboscis, which is used for sucking blood, consists of seven complicated parts. For example, the labrum has a hollow structure, and the maxillae have micrometer-sized tooth like projections on its tip. In this study, microneedles imitating one labium and two maxillae were fabricated using a precision three-dimensional laser lithography system “Nanoscribe.” The maximum length of the fabricated microneedle was 2.0 mm, the minimum length required to reach human capillary blood vessel underneath the epidermis.

Fabrication of 3D Photoresist Structure for Artificial Capillary Blood Vessel

We propose a new method for fabricating artificial capillaries using direct laser writing. IP-L and Ormocomp are tested as photoresist materials. Three different microstructures were fabricated from IP-L: a porous hollow pipe microstructure, a 3 × 3 array of twig microstructures, and an array of hollow twig microstructures. Porous hollow pipe microstructures of different diameters were fabricated from Ormocomp, a biocompatible photoresist. These designs resemble capillaries. IP-L and Ormocomp fabrication parameters, such as laser power, numerical aperture, fabrication time, and fabrication model, are compared. Fabrication time is related to the fabrication model chosen during the direct laser writing process. Combined model fabrication is recommended over solid model fabrication because it results in shorter fabrication time and a more robust microstructure that is more likely to maintain its shape on the substrate after development. Laser power is another important parameter controlling fabrication. IP-L fabrication withstands up to 20 mW of laser power, unlike Ormocomp microstructures, which require laser power of less than 18 mW. IP-L and Ormocomp photoresist stiffness is also evaluated. The fabrication of artificial capillaries is important in developing vascular simulators that enable researchers to understand, for example, blood pressure in the kidney glomerulus.