Q&A: Gassing up bioengineered materials for wound healing

UNIVERSITY PARK, Pa. — Biomaterials are specifically engineered to support tissue, nerve and muscle regeneration across the body, yet physicians and researchers have limited control over the size and connectivity of the internal pores that transfer oxygen and vital nutrients to where they are most needed. To solve this problem and better support tissue regeneration, a team at Penn State has designed a new class of tunable biomaterials.

Led by corresponding author Amir Sheikhi, the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biomaterials and Regenerative Engineering and associate professor of chemical engineering, the team developed a highly porous, light-weight biomaterial and tested its effectiveness both in test tubes and in mice. They found that their compound — a refined class of a foam-like material known as aerogel — offered improved cell infiltration, which may help rapidly form new blood vessels and regenerate damaged tissue in the body. The researchers published their research in a recent issue of Biomaterials.

In this Q&A, Sheikhi and Dino Ravnic, professor of surgery and co-author on the paper, shared how the new material could provide a more adaptive approach to caring for wounds and burns.

Q: What is aerogel? How is your new class different than previous aerogel materials?

Sheikhi: Aerogels are ultralight, oxygen-rich materials with enormous internal surface area, meaning they can store and transport many cells. Aerogel is attractive for applications like wound healing and tissue regeneration because they are mostly air, which helps oxygen and nutrients efficiently move around. However, traditional aerogels do not offer precise control over pore architecture at the cellular scale, which in regenerative medicine, is critical to controlling the interconnected pathways cells use to move, form blood vessels and integrate with surrounding tissue.

We developed what we call granular aerogel scaffolds (GAS). Instead of forming aerogels conventionally, we assemble them from size-controlled, protein-based microparticles — building blocks we can precisely tune. By changing the size of these building blocks, we can program the pore geometry and interconnectivity of the scaffold that serves as the aerogel's foundation. This allows us to adjust pore size without impacting the material’s stiffness and avoid structural collapse during drying, limitations that have historically constrained aerogel performance in regenerative medicine.

Q: What benefits does aerogel offer for health care applications compared to other biomaterials?

Ravnic: To be clinically useful for tissue repair, biomaterials must undergo cell infiltration and vascularization upon implantation, meaning cells must be able to interface with and form new blood vessels alongside the material. If vascularization cannot occur with the material present, tissue repair is not possible, which can lead to patient disease, reoperation and increased health care costs. This is especially problematic in wounds that suffer from low oxygen tension and limited potential for new blood vessel growth at baseline, such as irradiated, diabetic and burn wounds. Aerogels could offer an alternative for these at-risk patient populations who currently have limited treatment options.

Q: How did collaboration between physicians at the Penn State College of Medicine and your team of engineers influence the project?

Sheikhi: This project is an example of engineering informed by clinical need. Engineers can design materials with almost any property, but clinical insight allows us to optimize for practical use. My lab identified a problem in aerogel biomaterials — the lack of precise control over just a material’s pore features — invented GAS to address this challenge, and conducted in vitro and basic in vivo experiments to test various aspects of GAS, meaning we tested the material both in the lab and living models. We then worked closely with Dr. Ravnic and the surgical team to optimize for what matters biologically: rapid vascular ingrowth, where new blood vessels grow into tissues.

We rigorously tested performance and the process offered a detailed view into how our material would behave and support blood vessel growth in a physiologically relevant environment. This feedback loop, which was facilitated by the surgical team, is key in translating our work towards future use in healthcare settings.

Q: How can this material be applied in the near term? What could it offer in the future?

Ravnic: After more research and testing, aerogels could potentially play a substantial role in the treatment of non-healing wounds. Further in the future, aerogel scaffolds could be preloaded with specific cell types, such as muscle or skin, to develop patient-specific tissue engineered replacements. In this sense, aerogels could offer a platform technology for both tissue repair and regeneration. For reconstructive surgeons, such as myself, this represents the holy grail in treating patients who suffer from tissue loss, irrespective of the cause of their wounds.

Q: What’s next for this work? Are there plans to commercialize this material in the future?

Sheikhi: The next step in our research is to expand applications and evaluate long-term performance. We’re working on adding biochemical cues, factors that help cells grow or manage immune responses, into this adjustable platform. The shelf-stable nature of GAS is particularly exciting from a commercialization standpoint — the material can be dried, sterilized, stored and rapidly rehydrated without losing pore architecture or mechanical properties.

We are actively exploring pathways toward clinical translation, like obtaining patents and forming industry partnerships, as we are deeply interested in advancing this technology beyond proof-of-concept studies. Ultimately, our goal is not just to design better biomaterials for testing in the lab, but to translate them into accessible solutions that improve the care of real-world patients.

More information

Additional co-authors affiliated with Penn State include Saman Zavari, a chemical engineering doctoral candidate; Ji Ho Park, a resident surgeon in the Penn State College of Medicine; Mohammad Hossein Asgardoon, a postdoctoral researcher at the Penn State College of Medicine; Alexander Kedzierski, a bioengineering and biomedical engineering graduate student at the time of research who is now a doctoral candidate at the Georgia Institute of Technology; Arian Jaberi, a chemical engineering doctoral candidate; Anton Markus Hjaltason, an undergraduate chemical engineering researcher at the time of research who is now a chemical engineering doctoral candidate at the University of Minnesota; and Yuanhui Xiang, a postdoctoral scholar at the time of research who is now working at Alcon.

Sheikhi is the founding director of the Bio-Soft Materials Laboratory.

This work was supported by the National Institutes of Health’s National Heart, Lung and Blood Institute and the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair. Additional support was provided through the Leighton Riess Graduate Fellowship in Engineering, the E. Michael Ackley Jr. Graduate Fellowship Endowment and by the Max M. Snyder Graduate Scholarship in Engineering.

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