When patients undergo reconstructive surgery for devastating injuries, one of the biggest obstacles surgeons face is restoring blood supply to the repaired tissue. Without a functioning vascular system, new grafts cannot survive. With a new $3 million grant from the National Institutes of Health, researchers at Penn State are taking on this challenge by combining advanced 3D bioprinting with a novel surgical method, known as micropuncture.
Bioprinting is a form of 3D printing, but instead of using plastic or metal, it uses living cells and biomaterials to build tissue-like structures. Think of it as a high-tech printer that can carefully place different kinds of cells layer by layer, creating shapes that mimic real body parts. Researchers can design tiny channels, scaffolds or even whole sections of bone or skin that living cells grow into, making the printed piece more like natural tissue that can survive and function once implanted.
The research is led by Ibrahim Ozbolat, Dorothy Foehr Huck and J. Lloyd Huck Chair in 3D Bioprinting and Regenerative Medicine and professor of engineering science and mechanics, of biomedical engineering and of neurosurgery, and Dino Ravnic, professor of surgery and the Dorothy Foehr Huck and J. Lloyd Huck Chair in Regenerative Medicine and Surgical Sciences at the College of Medicine. Together, they aim to change how surgeons approach rebuilding damaged tissue.
"The grant is addressing one of the major issues, which is vascularization," Ozbolat said. "Repairing tissues and organs depends on how well vascularization is provided to them, so that you can have blood supply move right through those structures, and you can keep the cells viable. Otherwise, without vascularization, the tissue will die."
Most past approaches, Ozbolat noted, have not solved this fundamental challenge.
"Growing vessels is a big problem," he said. "There have been those who have been successful in part, but still, the blood vessels grow randomly and not really controlled."
Random blood vessel growth is not sufficient for reconstructive surgery due to uneven healing and even can lead to parts of the tissue dying. To overcome this, Ozbolat's lab is using 3D bioprinting to direct exactly how vessels grow.
"Can we really control that vascularization in a sense that we can guide how the vessels grow, and then we can control the orientation?" Ozbolat said. "In the meantime, can we speed up that vascularization? The answer to these questions is having the orientation is controlled by the 3D printing processes."
In this case, the bioprinting provides a kind of roadmap for vessels.
"The 3D printing basically enables us to make a structure that will have some templates for vessels to grow through," Ozbolat said. "Think about a mold of a biomaterial that we 3D print, and this mold has some vascular channels in it. Then we basically guide the blood vessels growing through these openings. We can make Y channels. We can make straight channels. So, when you have the straight channel, the vessel grows straight. When you have the Y, we envision that we can make something that branches."
Alongside bioprinting, the project will incorporate Ravnic's surgical innovation called micro-puncture. Using an ultra-fine needle, tiny holes are made in existing blood vessels, triggering natural sprouting of new vessels.
"We found that when we create these very small punctures, blood vessels rapidly sprout out of them," Ravnic said. "By combining this with Ibrahim's printed scaffolds, we can actually guide where those vessels grow and help them connect to the implant much more effectively."
The two approaches - bioprinting templates and micropuncture - work hand-in-hand, and the potential has shown itself in early testing, the researchers said, pointing to early experiments in a rodent model.
"We actually created those little holes, micropunctures on the sagittal sinus vein. It's the largest vein on the brain," Ravnic said. "Right on top of the holes, we put the structure that we 3D printed. And then through the micro puncture holes on the blood vessel, vessels sprouted and grew. And then via the 3D printed template, we actually guided their direction."
The research team is testing the approach in animal models. While clinical use is still in the future, both researchers said they see the potential for the grant to transform patient outcomes, especially when it comes to severe skull and facial injuries.
"Our goal is to develop solutions that can restore form and function for patients who have suffered devastating injuries," Ravnic said "If we can make engineered tissues that survive and thrive in the body, the impact could be lifechanging. We envision a future where surgeons will not only repair but truly rebuild the human body."
