Medical Device Daily National Editor

The anterior crucial ligament known to us more often these days as the ACL.

We hear about ACLs torn and gone terribly bad all the time, and we will be getting many more of such reports over the next few weeks as football (the American version, specifically) heats up.

The problem: shear forces on the knees, from the torsion after running into people or being run into tearing soft tissues from bone, and having to attach them back together again.

Now mechanical engineering researchers at the Georgia Institute of Technology (Georgia Tech; Atlanta) say they have developed a technique for better integrating soft and hard tissues such as these.

Science has long been able to produce artificial bone or artificial bone-like materials. But the hard part is integrating these hard materials with the soft materials of the human body. Focused on doing this, the researchers report that they have used skin cells to create artificial bones that mimic the ability of natural bone to blend into other tissues, such as tendons or ligaments or as an abstract of this research says, creating "interfacial zones that mimic the cellular and microstructural characteristics of native tissue."

Andres Garcia, PhD, a professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech, heads this research, with the goal to create "a graded continuous interface, because anatomically that's how the majority of tissues appear, and there are studies that strongly suggest that the graded interface provides better integration and load transfer."

He termed this a major challenge of regenerative medicine.

The artificial bones created by his group are described as displaying a gradual change from bone to softer tissue rather than the sudden shift of previously developed artificial tissue. This therefore provides better integration into the body for improved handling of weight and the shear forces the body must withstand, especially in athletic activity.

Garcia, who is focused primarily on mechanical engineering's applications in biomedical uses, told Medical Device Daily that the researchers used skin cells from rats in this research, with the bone material then implanted into rats.

"However," he added, "we have shown that we can modify human skin cells into osteoblasts."

He said that his team was able to implant the technology in vivo in periods up to two weeks. The first implantation was subcutaneous, with the next step to be, he said, "tendon-bone graft in a functional model."

The tissue was created by coating a 3-D polymer scaffold with a gene delivery vehicle that encodes a transcription factor known as Runx2. The researchers applied this in a way to generate a high concentration of Runx2 at one end of the scaffold and then decreased that amount until they ended up with no transcription factor on the other end. This created a spatial gradient of Runx2.

Garcia further described Runx2 as a transcription factor "that controls the expression of several osteoblast-specific genes and regulates mineralization. The Runx2 knock-out model has no mineral in the bones."

In the next step, the researchers seeded the skin fibroblasts uniformly onto the scaffold. The skin cells on the parts of the scaffold containing a high concentration of Runx2 turned into bone, while the skin cells on the scaffold end with no Runx2 turned into soft tissue.

Assuming further success with the technology, the researchers specifically pointed to ACL repair as one prime application of this technique.

"Oftentimes, ACL surgery fails at the point where the ligament meets the bone," they said in a statement. "But if an artificial bone/ligament construct with these types of graded transitions were implanted, it might lead to more successful outcomes for patients."

Former graduate student Jennifer Phillips, Garcia's co-lead researcher on the project and now working as a post-doctoral research fellow in developmental biology at Emory University, another prestigious Atlanta institution said, "Every organ in our body is made up of complex, heterogeneous structures, so the ability to engineer tissues that more closely mimic these natural architectures is a critical challenge for the next wave of tissue engineering."
Now that the research team has been able to demonstrate that they can implant the tissue in vivo for up to two weeks, the next step will be to show that the tissue can handle weight for longer periods of time in a "functional" model, Garcia said.

He said it is still much too early to project when the strategy might be attempted in a human being and that the next step would be to use the technique in a sheep or goat.

The research appears in the Aug. 21 edition of the Proceedings of the National Academy of Sciences.