Feb 28, 2025

Could 3D-printed air revolutionize bioprinting?

A novel technique for creating voids and channels within bioprinted living tissues could help break the vascularization barrier, unlocking the next generation of medical applications for the technology.

As the Huck Chair in 3D Bioprinting and Regenerative Medicine and Professor of Engineering Science and Mechanics at Penn State, Ibrahim Ozbolat aims to harness the power of 3D bioprinting to advance personalized medicine and drug discovery, and to ultimately help create life-saving tissues and organs. His work, which bridges fields as diverse as engineering, surgical medicine, mathematics, and vascularization.

“Two of the biggest challenges in bioprinting for regenerative medicine are scalability and vascularization, and they are related, said Ozbolat. “The current limit when bioprinting living cells is one centimeter, in terms of thickness. To scale up from there requires that the tissue be vascularized, or else the cells die. So the creation of voids or channels within the living material is absolutely essential to further advance this field.”

The primary technique currently used for vascularization involves the use of sacrificial inks, which are printed and later removed to create empty channels. This approach presents several limitations, including the need for extensive post-processing, difficulties in removing inks from delicate structures like narrow blood vessels, and potential biological interference from ink residues.

Ozbolat’s new approach promises to overcome these limitations by using air as a new “ink.” His innovative 3D Air Printing (3DAirP) technology leverages the compressibility of air within yield-stress gels to create open, stable channels in a single step. These channels, which mimic the function of blood vessels, can be printed up to twenty times faster than traditional methods, offering a much-needed solution to the vascularization bottleneck in tissue engineering.

To achieve this boldly imaginative innovation, as well as others over the course of his career, Ozbolat has relied on a team of experts from a range of different fields. One of his long-term research partners is Dr. Dino Ravnic, Huck Chair in Regenerative Medicine and Surgical Sciences and professor of Surgery at Penn State’s College of Medicine.

“Biomedical engineers and surgeons are particularly well aligned to tackle the problems of tissue and organ loss collaboratively,” explained Ravnic. “Ibrahim’s background forces me to think more like an engineer and my clinical background forces him to think more like a surgeon. Ultimately, a balance is struck that is technically feasible, biologically relevant and clinically translatable.”

“Dino’s an expert with clinical insights,” added Ozbolat. “Most surgeons just do surgery, but he provides intellectual insights into how to do the work better. This has a major impact on the decision-making process.”

Another key collaborator on Ozbolat’s team is Professor of Engineering Science and Mechanics Francesco Costanzo, whose mathematical and computer modeling skills are a crucial component for applying the experimental 3DAirP technology.

“The mathematics must be able to represent flows and deformations and, above all, predict the stability of the bio-printed structures,” said Costanzo of the project. “This expertise is required whenever one intends to study applications that would be very hard or too expensive to explore by direct experimental methods. It’s a formidable challenge, but one that I enjoy very much.”

“Francesco’s expertise is critical to this new technique we are developing, especially in terms of tissue mechanics,” said Ozbolat. “Using computer models and simulations, he can predict the mechanical stress involved, which is essential for setting appropriate parameters for our processes.”

Ozbolat’s team aims to generate vascular channels as narrow as 125 micrometers, a crucial size for enabling blood flow in engineered tissues. The technology will be tested through two key applications: the creation of scalable vascularized bone tissue and an atherosclerosis model on a chip. These demonstrations will showcase the potential of 3DAirP in advancing regenerative medicine and enhancing the study of diseases like atherosclerosis.

In a groundbreaking second aim of the project, Ozbolat is exploring the potential for 3DAirP to be used in surgical settings. By developing a portable version of the technology, Ozbolat hopes to enable intraoperative generation of vascular channels in real time.

Two pilot applications are being tested: using 3DAirP to create air channels within bioprinted bone constructs during surgeries on rat calvarial defects and coupling the technology with a microsurgery technique to stimulate angiogenesis and promote vascular ingrowth in rat hindlimbs.

This transformative research, made possible through Ozbolat's unique collaborations with experts across multiple disciplines, has the potential to revolutionize how we approach tissue engineering, organ regeneration, and even surgical interventions. The team’s work brings together a wealth of expertise in bioprinting, surgical techniques, biomaterials, biomechanics, and more—each contributing to the potential realization of a future where scalable, vascularized tissues and organs can be printed for clinical use.

Furthermore, the ability to create vascularized tissues on demand could accelerate drug testing, disease modeling, and personalized medicine, ushering in a new era of precision healthcare.

In sum, this innovative approach to 3D bioprinting may help unlock life-saving technologies that were once confined to the realm of science fiction. Through this groundbreaking research, Ibrahim Ozbolat and his team are not just advancing science—they are paving the way for the future of regenerative medicine.