Fabrication of Hollow Structures in Photodegradable Hydrogels Using a Multi-Photon Excitation Process for Blood Vessel Tissue Engineering.

Kenji Torizuka,Yoichiroh Hosokawa,Taku Satoh,Uran Watanabe,Shinji Sugiura,Toshiyuki Takagi,Masayuki Kakehata,Fumiki Yanagawa,Kimio Sumaru,Masato Tamura,Toshiyuki Kanamori

doi:10.3390/mi11070679

Abstract

Engineered blood vessels generally recapitulate vascular function in vitro and can be utilized in drug discovery as a novel microphysiological system. Recently, various methods to fabricate vascular models in hydrogels have been reported to study the blood vessel functions in vitro; however, in general, it is difficult to fabricate hollow structures with a designed size and structure with a tens of micrometers scale for blood vessel tissue engineering. This study reports a method to fabricate the hollow structures in photodegradable hydrogels prepared in a microfluidic device. An infrared femtosecond pulsed laser, employed to induce photodegradation via multi-photon excitation, was scanned in the hydrogel in a program-controlled manner for fabricating the designed hollow structures. The photodegradable hydrogel was prepared by a crosslinking reaction between an azide-modified gelatin solution and a dibenzocyclooctyl-terminated photocleavable tetra-arm polyethylene glycol crosslinker solution. After assessing the composition of the photodegradable hydrogel in terms of swelling and cell adhesion, the hydrogel prepared in the microfluidic device was processed by laser scanning to fabricate linear and branched hollow structures present in it. We introduced a microsphere suspension into the fabricated structure in photodegradable hydrogels, and confirmed the fabrication of perfusable hollow structures of designed patterns via the multi-photon excitation process.

Highlights

In recent years, the cost of drug development has increased exponentially [1], and the success rate of clinical trials has been decreasing every year [2]
We explored the composition of the photodegradable hydrogels that were resistant to size change (Table 2, Figure 3)
We developed a novel method to fabricate the designed hollow structures in photodegradable hydrogels prepared in a microfluidic device in programmed manner

Summary

Introduction

The cost of drug development has increased exponentially [1], and the success rate of clinical trials has been decreasing every year [2]. One of the reasons for this is that the results of animal experiments cannot be directly extrapolated to clinical trials due to the difference in species between animals and humans Under these circumstances, expectations for in vitro assays using cultured cells of human origin are increasing, and in particular, microphysiological systems (MPS), which are biomimetic devices using microfabrication technology, are receiving immense attention. Blood vessels carry oxygen and nutrients in the body [3], but are greatly involved in angiogenesis and invasion of cancer [4] They are related to drug delivery and pharmacokinetics, and engineered blood vessels are assumed to be used in drug discovery as a novel MPS. It is necessary to evaluate multiple compounds at different concentrations for drug development, and a multithroughput format, ideally an array format, of the 3D vascular model is required for use in drug discovery

Methods

Results

Conclusion