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Exclusive interview with growers of 3D tissue

Article Date: 22 Jul 2013 – 4:00 PDT

Researchers have taken technology from makers of mobile phones and other consumer electronics and used it to grow 3D tissue.

Scientists at the Draper Laboratory and the Massachusetts Institute of Technology (MIT) have created a prototype using an automated “layer-by-layer” assembly method – usually found within the electronics packing industry to build integrated circuits. Their work is published in the journal Advanced Materials.

Instead of building mobile phones, this technology has been used to stack “porous, flexible, biodegradable elastomer sheets,” which the researchers have used to create 3D scaffolds on which tissues can be grown.

Exclusive interview

Medical News Today spoke exclusively with the researchers. The interview follows here. Skip to the rest of the original news story.

How did you come up with the idea of the tissue scaffolding?

Lisa Freed, of Draper Laboratory and principal investigator of the study, says:

“Cardiac muscle requires robust structural and mechanical properties to contract continuously and efficiently while resisting fatigue. Natural muscle fibers meet these demands via a unique ensemble of cellular and extracellular matrix structures.”

“While many types of scaffolds have been developed and combined with cells in an effort to recapitulate natural muscle fibers, few scaffolds have been explicitly designed with natural muscle architecture in mind.”

“As attention turns towards clinical applicability, limitations intrinsic to previous scaffolds are becoming more apparent, such as the random structures of gelatinous and foam-like materials, and mechanical weakness and/or excessive stiffness of other materials.”

“Microfabrication techniques, such as micromolding and layer-by layer assembly, provide new opportunities to fabricate tissue-engineering scaffolds with controlled architecture in 3D.”

“As such, we thought of designing scaffolds with a more muscle fiber-like architecture by combining these technologies.”

What is your next step?

Lisa Freed:

“Our next goal is to extend in vivo studies to implanting scaled-up engineered tissues on the surface of rat hearts after heart attack.”

“A related next goal is to demonstrate that we not only have created tissue with a similar architecture to heart tissue, but that it also has similar function, and better function than other, previously developed engineered heart tissue.”

“The long term goal is to create viable, thick cardiac tissue implants, for example by combining elastomeric building block scaffolds with cultured heart cells and slowly biodegradable perfusable channel network.”

How will this research help future developments?

Martin Kolewe, a postdoctoral research associate at MIT, says:

“A common thread across many organs which are targets for regenerative medicine applications is that their tissues have an extremely complex 3D architecture.”

“The technology we have developed allows us to access an entirely new 3D design space to try and replicate this architecture in tissues including all three types of muscle (cardiac, skeletal, smooth) as well as tendon, nerve, and even potentially liver and bone.”

“So this research brings us one big step closer to creating engineered tissue that has the same structure of native tissue, and which may eventually be more useful in the clinic.”

“Another key impact of this research moving forward is that it is a practical way to assemble polymer scaffolds to produce large, complex tissue constructs.”

“One major challenge to achieving clinical relevance of engineered tissue is the size of functional tissue we can currently produce.”

“While there are several challenges to producing thicker tissue, including the need to keep the tissue alive (accomplished via a microvasculature in native tissue), the approach developed here will allow us to build scaffolds and devices with complex designs in scalable manner.”

How could this technology help in rebuilding or growing human organs?

Martin Kolewe:

“To help repair human organs, cell-free polymer scaffolds built with this technology could be used to guide native tissue regrowth in certain types of tissue or provide precisely designed structural and/or mechanical support in other cases.”

“For these applications, bringing the technology to humans is a matter of choosing appropriate targets, tuning biomaterial properties, and working through animal models. We have the major pieces of technology at our disposal.”

“However, in order to rebuild human organs in vitro, an appropriate human-derived cell source must be developed that can provide both long-term survival and specific functionality.”

“While various stem cell and progenitor cell types are the subjects of extensive research, demonstration of an appropriate cell source remains a major challenge in the regenerative medicine field.”

Original news story continued

Lisa Freed, of Draper Laboratory and MIT, says that this new technology could be implemented to encourage growth or regrowth of certain tissues in people suffering from congenital defects or serious damage to tissues and organs.

The scientists say the 3D device will allow them to build controlled “3D pore networks” that guide cells to grow in precise patterns, in the way that highly specialized tissues such as heart and skeletal muscle grow.

3D Tissue The 3D scaffolds will enable scientists to grow fully functional tissue by allowing cells to grow in precise patterns. Photo credit: MIT. “Cells in a human heart rely on a variety of spatial and chemical cues to form the hierarchical organization that results in a complete and functional organ,” the researchers say. To ensure the cells grew in these precise patterns, the scientists had to identify “key structural cues” that they could replicate in the lab.

Having developed their 3D scaffolding technique, the research team was able to grow contractile heart tissue from rat heart cells.

The scaffolds are flexible enough, the researchers say, to be implanted directly into an injured part of the body in order to guide cellular growth at that site.

Lisa Freed says:

“Scaffolds that guide 3D cellular arrangements can enable the fabrication of tissues large enough to be of clinical relevance, and now we have developed a new tool to help do this.”

Biomedical researchers could also use these scaffolds to their advantage in order to study tissue development, the study authors say.

It is thought that this new technology will mark a big improvement on current methods of repairing and growing human organs. Prior to this innovation, researchers relied on 2D templates, amorphous gelatin, or 3D pore structures that were unable to focus on a particular area of growth.

The researchers hope this technology will assist researchers in exploring new treatments and research possibilities.

Martha Lundberg, a program director at the National Heart, Lung and Blood Institute (NHLBI), says of the research:

“This work could be a potentially significant advance in tissue engineering that will lead to new tissue-based therapies aimed at restoring organ function.”

Written by Honor Whiteman

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