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Dean, colleagues working to make tissue engineering cheaper, more scalable

Live/Dead staining of human adipose derived stem cells at the end of the 21 day experiment in complete growth medium, osteogenic differentiation medium, and adipogenic differentiation medium at 10x magnification. All scaffolds supported viable cell growth in all tested media for the duration of the 21-day experiment.

Live/Dead staining of human adipose derived stem cells at the end of the 21 day experiment in complete growth medium, osteogenic differentiation medium, and adipogenic differentiation medium at 10x magnification. All scaffolds supported viable cell growth in all tested media for the duration of the 21-day experiment. Photo courtesy of Stephen Tuin.

Tissue engineering is one of the fundamentals of the field of biomedical research, and College of Engineering Dean Elizabeth Loboa and her colleagues at the University of North Carolina and North Carolina State University recently illustrated a way to make the process cheaper and more scalable.

The process uses artificial fibers to create engineered scaffolds, which are seeded with stem cells that grow to replace the missing tissue. The scaffold eventually degrades away, leaving natural tissue in its place. Typically, nonwoven materials are used in the scaffolding process, and they’re usually bonded through a process called electrospinning, whereby an electrostatic field draws nanofibers from a solution and bonds them together. This process is effective, but large-scale production isn’t currently efficient or cost-effective.

Alizarin Red S calcium staining for all nonwoven fabrics types evaluated as tissue engineering scaffolds for hASC at 10x magnification.  Calcium deposits appear dark red after staining.  All fabric types exhibited the presence of intense calcium staining when treated with ODM, indicating the presence of an osteogenic phenotype.

Alizarin Red S calcium staining for all nonwoven fabrics types evaluated as tissue engineering scaffolds for hASC at 10x magnification. Calcium deposits appear dark red after staining. All fabric types exhibited the presence of intense calcium staining when treated with ODM, indicating the presence of an osteogenic phenotype. Photo courtesy of Stephen Tuin.

“The challenge with that is you have something that’s very difficult to scale up,” Loboa said. “We can run our system for hours and create about a six-inch diameter of scaffold material. In the context of scale-up, you need to be able to create hundreds of meters of material that you can replicate, duplicate, that constantly looks the same so you can use it clinically and not ever have it vary.”

Loboa worked with Stephen A. Tuin, a recent doctoral graduate from her research group at the Joint Department of Biomedical Engineering at UNC and NC State, and Behnam Pourdeyhimi of the NCSU College of Textiles to publish a pair of papers — “Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds in Biomedical Materials and “Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications” in Acta Biomaterialia.

The papers collectively show that three common textile creation methods — meltblowing, spunbonding and carding — can produce effective scaffolds that retain biomimetic behavior, allowing for mechanical properties that better mimic native tissue.

“The problem with electrospinning is you’ve got weak fibers, heterogenous scaffolds, very small pore sizes — leading us to ask is there a way to use standard manufacturing approaches that we use in other industries?” Loboa said. “So we looked at textiles and compared very common methods in textiles to create a variety of products.”

Portrait of Elizabeth Loboa

Elizabeth Loboa partnered with Stephen A. Tuin, a recent doctoral graduate of the Joint Department of Biomedical Engineering at UNC and NC State, and Behnam Pourdeyhimi of the NCSU College of Textiles to publish a pair of papers. What the papers collectively show is that three common textile creation methods can produce effective scaffolds that retain biomimetic behavior, allowing for mechanical properties that closely mirror native tissue.

Meltblowing is a technique by which the nonwoven materials are created using a molten polymer drawn through tiny gaps in order to create continuous fibers. Spunbond materials are made much the same way, though as opposed to meltblowing, the fibers are drawn into a web while in a solid state instead of a molten one. Carding involves the separation of fibers through the use of rollers, forming a web of sorts.

Loboa and her colleagues used these techniques to create polylactic acid (PLA) scaffolds — a Food and Drug Administration-approved material — seeded with human adipose derived stem cells (hASCs) and cultured in complete growth medium (CGM) for a week. They then spent three weeks studying viable cell proliferation within the scaffold and cell differentiation along both a fat and bone pathway. The results illustrated that the three scaffold manufacturing methods proved as viable if not more so than electrospinning for promoting desired cell viability, proliferation and differentiation.

The research showed that a small sample of electrospun material could cost between $2-5, whereas the cost would be $1-2, $.30-3 and $.10-3 for meltblown, spunbond and carded scaffolds, respectively.

The next step is testing how the different scaffolds perform their duties once implanted in animals. The goal eventually is to bring such nonwoven products to clinical practice by making them increasingly efficient and cost-effective.