Creating Vascular Structures Using Low Cost Desktop 3D Printers

In a thesis entitled “Engineering of vascular networks within biocompatible hydrogels using 3D printing technology,” a PhD student named Juan Liu discusses the need for new technologies in wound healing. While skin flaps and grafts are the “gold standard” in clinical treatment of large skin and subcutaneous tissue defects, there are many complications that can arise from these treatments, and there is also the issue of not having enough skin to be able to harvest to cover particularly large wounds.

3D printing, however, using stem cells, allows for an unlimited amount of tissue to be created to heal large wounds. Using cells from the patient reduces the risk of rejection, as well. In order to create and maintain live tissue, however, vascularization is required, meaning that blood vessels need to be established, which is the tricky part of tissue engineering. Liu hypothesizes that open source desktop 3D printing technology can be used to design and fabricate “customized bio-artificial multicellular tissues with embedded vessel-like supply channels and corresponding bio-reactors for long-term 3D tissue culture.”

Liu outlines the following objectives:

• Use open source software to design 3D tissues with vascular patterns and fabricate them with desktop 3D printers
• Analyze cell survival and function over time in 3D tissues in respect to vascular patterns
• Generate 3D printable bioreactors that allow online monitoring of the process
• Prevent shrinking of 3D tissues
• Generate multilayer 3D tissues with different cell types

Liu goes on to demonstrate how 3D printing technology can be used to precisely form vascular structures within cell-laden hydrogels. He also creates “customized PLA and PDMS bioreactors for continuous perfusion and real-time operation.” The vascular structures formed within the cell-laded hydrogels, which were created by 3D printing, were able to increase the viability of the cells surrounding the vascular structures.

“In addition, the final system based on PDMS has been proven to sustain long-term 3D cell culture, which is the basic for 3D cell proliferation and tissue formation in vitro,” says Liu. “Among others this approach exhibits unique advantages to fabricate a hydrogel-based multilayer vascular device in a cost-effective and fast manner, which has a huge potential for viable 3D cell culture, complex tissue engineering, disease modeling as well as drug screening.”

This model, he continues, could also be used to mimic natural tissue architecture and create bigger multilayer hydrogel constructs with corresponding layers of functional cells to study cell morphology, differentiation, and potential function of engineered tissue constructs.

“Further optimization of the hydrogel concentration in each layer, cell density and perfusion parameters may enable the preparation of 3D vascular tissues under the conditions mimicking the natural environment with better functions and matrix compositions,” he adds. “In order to overcome the tendency of shrinking in soft hydrogels, combination with eletrospun fibers are promising. The system presented in this thesis allows fabrication of vascular networks in both soft and stiff cell laden hydrogels. It may serve as a novel platform for vascularized tissue engineering, that facilitates the generation of more functional, engineered vascular tissue. It may be useful for studies of wound coverage and tissue regeneration and eventually aid the treatment of wounds.”

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