Sep 7, 2017 | By David

The progression of 3D bio-printing techniques seems to be accelerating at a remarkable rate these days, and yet another significant breakthrough in the field was recently achieved by a group of Korean researchers. The team was led by Young Joon Hong, Sang-Mo Kwon, and Dong-Woo Cho, from Pohang University of Science and Technology and Pusan National University. They succeeded in creating a novel hybrid bio-ink which can be used to 3D print structures crucial to the treatment of various blood circulation-based conditions.

When circulation is restricted due to blockages or damage to blood vessels, this limited blood supply can lead to further damage of affected organs and tissues. The situation, known as ischemia, causes many diseases and affects people in a number of different ways, but treatments are still relatively limited. Cell-based therapies have often been applied, with varying degrees of success.

Many of the cell treatments for ischemic problems have made use of Endothelial progenitor cells (EPCs), in order to stimulate neo-vascularization. The problem with this is that the ischemic sites are often hostile to the EPCs, limiting their ability to survive and differentiate themselves due to low nutrition, oxidative stress, inflammation, and reactive oxygen species.

A solution to this problem is suggested by the use of what are known as de-cellularized extracellular matrices (dECMs). These are essentially the frameworks or skeletons of different organic tissues, with the cells removed. Because of their composition, structure, and biomechanical properties, they are ideally suited to encourage the survival and proliferation of cells in new environments.

Previous studies have used dECMs derived from a variety of different tissues to develop 3D printable bio-inks. These bio-inks were then successfully used to promote tissue function and cellular activities. The researchers from South Korea wanted to see if an ink based on a vascular dECM could similarly be used to treat vascular problems caused by ischemia. They created a hybrid bio-ink by mixing vascular dECM from a pig’s aortic tissue with sodium alginate hydrogel, which is a key element of 3D printable bio-inks.

The team then used this hybrid bio-ink and a 3D co-axial cell printing method to produce bio-blood vessels (BBVs). The easy scalability of 3D printing technology meant that they were able to create these BBVs in a range of different sizes for testing. The 3D printing system was designed specifically for the task by the researchers, and they made use of commercially available co-axial extrusion nozzles. After printing was complete, the vessels were incubated at 37 degrees Celsius for 30 minutes, which led to the dissolution of the hydrogel and left a hollow structure behind.

These hollow BBV tubes were tested in vitro, with cellular activity being measured on a regular basis. They were found to successfully promote viability, proliferation, and differentiation of EPCs. When compared to type-I Collagen, a more basic material used for similar purposes that was the control element in this experiment, the results were vastly superior.

The 3D printed BBVs were also tested out on laboratory mice whose hind limbs had undergone the effects of ischemia. The BBVs, implanted close to affected blood vessels, were found to promote a rapid recovery. As predicted before testing, they acted as a form of blood vessel graft, as well as a drug delivery system that provided an environment capable of stimulating the development of EPCs into functional vascular tissue.

The researchers foresee a number of applications for this promising research, the results of which were published in the Advanced Functional Materials journal. Potential new avenues now open to be explored with the help of their hybrid bio-ink include regeneration from ischemic diseases, replacement of injured blood vessels, direct building of pre-vascularized tissue/organs, and construction of vascular models and biochips.



Posted in 3D Printing Application



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