A Bioinspired Approach to Large Pediatric Osteochondral Injuries

The search for a better way to repair damaged cartilage came out of what Patrick Whitlock, MD, PhD, faced as an orthopaedic surgeon. After earning a PhD in bioengineering and spending two years of his orthopaedic residency studying regenerative medicine in the lab, he faced a problem for which there was no good answer.

“When I started doing hip surgery in young kids, I realized we don’t have a solution for them,” he says. Cartilage, the thin membrane of tissue critical for ease of movement in the hips and other joints, once damaged by disease or injury, doesn’t heal itself easily. That’s particularly true for larger injuries of 2 centimeters square or greater, the sort Whitlock was encountering.

Traditionally, the only solution for joints where large areas of cartilage are destroyed has been to replace the joint with something artificial. For young people, that’s particularly troublesome, since it means multiple replacements over a lifetime, with the accompanying trauma, expense and limitations that imposes. Whitlock believed there had to be a better way.

So he headed back to the lab. “It’s always easier to work on a problem that exists and try to find a solution. The clinical problem drives your research.”

His research led to a breakthrough idea for a type of artificial scaffolding that would dispense growth factors and proteins to injured cartilage, helping its regrowth. The idea earned him the 2017 Angela S.M. Kuo Award from the Pediatric Orthopaedic Society of North America.

“It’s a scaffold of biomaterial that can be formed into the shape of the defect,” says Whitlock. “Within the material we put biologic material derived from cartilage, which releases growth factors and proteins that drive the recipient cells to form bone and cartilage to repair the defect into which it’s placed.”

Whitlock developed the scaffold material with James Lin, PhD, a bioengineer at the University of Cincinnati (UC). They used a polymer based, printable plastic, poly (L-lactic acid) (PLA) and poly (caprolactone) (PCL), both already FDA approved. Each has properties necessary to be three-dimensionally printed into a shape specific to the injury. 

They mix the PCL filament with polylactic acid microspheres, which contain proteins that induce the formation of cartilage tissue.

“By mixing the two together, we protect the protein in the microsphere so it doesn’t melt [in the 3-D printing process],” says Whitlock. “It’s a two-phase material that has granules within it, and they stay intact. The large filament part hardens but the spheres are imbedded, and they release the growth factors and proteins over time.”

Whitlock says their data show that there is a rapid release of the growth factors within the first few days, then that continues over two to three weeks. “We would expect it to continue as the microspheres break down over time and are taken over by normal tissue. It gives the tissue mechanical support and gives a jump start to the regrowth process.”

Other current regrowth techniques rely on transplants of cadaver tissue, which isn’t easy to come by, or on using the patient’s own cells to make replacement cartilage, which is useful for smaller injuries but hasn’t had great success.

Whitlock credits colleagues in the UC College of Biomechanical Engineering for helping bring the idea to reality. Cincinnati Children’s and UC enthusiastically support collaborations on a number of tissue engineering projects.

“I would never have been able to execute this without the help of Stacey Gruber [a PhD student in bioengineering] and James Lin to develop a process to fabricate essentially a hybrid material. It could never have come to fruition without their knowledge. It has been a really good collaboration between the two groups.”

The researchers are just beginning studies in an animal model, and Whitlock is optimistic about what they will find. So far, he says, their in vitro data show that the 3-D scaffold holds up well and drives cells to grow cartilage.

His hope is to come away with a better solution that he and his orthopaedic colleagues can offer their young patients.

“Right now there are no really good options out there. This is a smart scaffold that supports and drives the growth of tissue at the same time. Other ideas have been really difficult to implement at every institution. We want something that’s easily reproducible.”

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