A Few Items of Tissue Engineering News

Tissue printing startup Organovo, of the Methuselah Foundation's portfolio of early stage investments, received a new round of funding recently:

Organovo closed a private placement consisting of approximately 6.5 million units of its securities to qualified accredited investors, for total gross proceeds of $6.5 million. "Organovo's advanced bioprinting platform can replicate essential biology for research, drug discovery and development and, eventually, for therapeutic applications," stated Keith Murphy, chief executive officer of Organovo. "We have found success in achieving early revenue through strategic collaborations, and this funding will allow us to extend the reach and uses of 3D bioprinting through growth and innovation in the coming years."

Given that at this stage in their life cycle they are essentially a research equipment manufacturer, that sort of money - while small in terms of medical development in the mainstream - should be enough to get them to the next level. You might recall an h+ Magazine article from a couple of years ago that gives a good overview of what the company aims to achieve:

Dr. Forgacs ultimately foresees fully implantable organs printed from a patient's own cells. "You give us your cells: we grow them, we print them, the structure forms and we are ready to go," he says. "I am pretty sure that full organs will be on the market [one day]." A printed biological heart might not appear exactly like an embryonic heart with a pericardium, two superior atria, and two inferior ventricles. But it will perform the same function: pumping blood throughout the blood vessels.

The second item relates to the preservation of organs for later transplant: this is a big logistical hurdle. A great deal of the processes of present day transplantation and early tissue engineering are completely shaped by our inability to reliably store large, complex tissues for the long term, without damage. The process of decellularization may be a practical way to work around the issue, though it remains to be seen if the economics work out yet: donated organs can be decellularlized, the scaffold stored at low temperature, and then warmed up and repopulated with a patient's cells in a matter of days. Here is a note from ScienceDaily, which leads to an open access research paper that is available in PDF format:

[Researchers] studied various strategies for freeze-drying porcine heart valves. After the cellular material was removed, they freeze-dried the heart valve scaffolds with or without sucrose and hydroxyl ethylene starch, and then compared the stability and elasticity of the freeze-dried scaffolds to assess the effectiveness of these lyoprotectants in preventing degradation of the scaffold. ... Tissue freeze-dried with sucrose alone displayed less porosity compared to tissue freeze-dried with the sucrose/HES mixture, whereas no significant differences in biomechanical properties were observed. Decellularization decreased the elastic modulus of artery tissue. The elastic modulus of freeze-dried tissue without protectants resembled that of decellularized tissue. The elastic modulus values of freeze-dried tissue stabilized by lyoprotectants were greater compared to those of decellularized tissue, but similar to those of native tissue.

Lastly for today, an article on one of the challenges of tissue engineering that people outside the field don't tend to think all that much about, which is that it is exceedingly difficult to convince tissues to form exactly the desired shape, with exactly the right mechanical properties, and with the right cells in the right place in that shape. A lot of researchers are spending a lot of time on determining how to cultivate tissue of the right size and shape; the strategies needed vary greatly by tissue type and other circumstances. In any case, here is an article on tubes:

In another advance for the field, researchers have now demonstrated a strategy to fabricate tubular structures with multiple types of cells as different layers of the tube walls. This method may be widely used in simulation of many tubular tissues and enriches the toolbox for 3D micro/nanofabrication by initially patterning in 2D and transforming it into 3D. ... To demonstrate the capability of their method, the scientists successfully simulated the structure of a human vessel-like structure - the tubular wall has three layers, and in each layer there is one representative type of cells: endothelial cells, smooth muscle cells and fibroblast cells (from inside out). This kind of tubular structure with multiple types of cells can be applied in tissue engineering such as arterial and venous grafts in vivo. And [the] preparation method of stress-induced rolling membrane can be applied to fabricate other self-assembled 3D structures.

You might compare the methodologies in the technology demonstration quoted above with the approach used in growing mouse teeth to get a sense of just how broad the range of necessary techniques is.

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