Soft tissue restoration, focus on vascular formation grant $3 million

UNIVERSITY PARK, Pa. — The ability to regenerate and form blood vessels, a literal lifeline that extends deep into soft tissue, remains an elusive milestone in regenerative medicine. Known as tissue revascularization, stimulating blood vessel growth and pattern formation in damaged or diseased tissue could accelerate the field of regenerative medicine, according to Penn State researchers.

With a four-year, $3 million grant provided by the National Institutes of Health’s National Heart, Lung, and Blood Institute, Penn State chemical engineering and reconstructive surgery researchers plan to develop new ways to help restore soft tissue loss in patients through two coordinated revascularization techniques.

“Tissue revascularization is a bottleneck for regenerative medicine,” said the lead investigator Amir Sheikhi, assistant professor of chemical engineering at the College of Engineering, which is also affiliated with biomedical engineering. “This is an important award for the entire field, as we hope to develop a fundamentally new way of tackling this problem by using cross-disciplinary teams.”

When repairing a traumatic injury, the surgeon must be able to quickly restore blood flow to the engineered graft, flap, and scaffold. However, this is not always possible using conventional techniques, according to the researchers.

The researchers plan to combine a class of protein-based granular hydrogel biomaterials pioneered by Sheikhi, with a microsurgical tactic known as vascular micropuncture, which the principal investigators co-developed. Dino RavnikHuck’s Chair of Regenerative Medicine and Surgery, professor of surgery at Penn State College of Medicine, and a plastic surgeon at Penn State Health Milton S. Hershey Medical Center.

Bulk hydrogel scaffolds — polymer networks that can hold large amounts of water while retaining their structure — have been used over the past decades as platforms for restoring soft tissue during surgical repair, according to Sheikhi, but they often suffer from slow and random vascularization. effect on implantation.

To overcome the limitations of bulk hydrogels, Sheikhi said he plans to engineer protein-based granular hydrogel scaffolds by attaching microscale hydrogel particles to each other.

“By adjusting the empty spaces between the hydrogel particles, we can regulate how cells interact with each other and assemble, guiding tissue architecture and the formation of new blood vessels,” said Sheikhi.

At the same time, the researchers will apply vascular micropuncture, in which Ravnic and his team will puncture blood vessels with microneedles to speed up the formation of new blood vessels. The small needle size ensures no significant blood clots or bleeding.

“Our microsurgical approach allows targeted formation of blood vessels without the use of any additional growth factors or molecules,” said Ravnic. “This is very relevant for advancing tissue engineering and also in treating vascular-related conditions.”

The researchers will first test their approach using human cells cultured in vitro from patient samples. Once they build a basic understanding of the approach at the cellular level, they will test it in rodents.

The combination of the two techniques, the researchers predict, will allow new blood vessels to form quickly in an architecturally organized way. Hierarchical formation – the organization of blood vessels from large to medium to small – helps regulate blood flow, disperse oxygen, and modulate immune cells throughout reconstructed or injured soft tissue.

“The vein pattern should resemble tree branches, with a large trunk that widens into progressively smaller branches,” says Sheikhi. “The reason is that blood needs to flow from the main vessels deep in the tissue through the capillaries.”

Shayn Peirce-Cottlerprofessor and chair of biomedical engineering at the University of Virginia, will collaborate on the grant.