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Guan explores injectable therapies

Jianjun Guan's lab group

For generations, healing medicines have come from the tip of a hypodermic needle, but materials scientists at The Ohio State University are developing ground-breaking technologies to pass through that needle.

Associate Professor of Materials Science and Engineering Jianjun Guan will lead two projects—funded by the National Institutes of Health (NIH)—to devise injectable therapies that could make recoveries shorter and lives longer.

Guan and colleagues will direct $1.1 million of the NIH funding to stem the progression of tissue damage after a heart attack.

“Heart attacks form a scar on the heart,” Guan explained.  “The scar expands over time, and the heart cannot self-repair.”

The fibrous scar tissue spreads to supple, healthy parts of the heart, damaging it and limiting the heart’s ability to function. Guan and his colleagues in the Ohio State College of Medicine want to stop the spread of scar tissue from its inception.

To do that, they’re developing new injectable materials for use after a heart attack that can control tissue response. They plan to combine a hydrogel with a new drug that, when injected into the scar tissue, will arrest its growth.

“The procedure is currently conceived for open-heart surgery, but with the success of this phase, we’d move on to develop nanomaterials that would aggregate in the heart naturally and release drugs as needed,” Guan said. 

“Approximately 5.5 million people in the United States have heart failure,” Guan said. “There are 8 million heart attack patients, with another 800,000 every year.”

An additional $410,000 from the NIH will be used to help clinicians track patient recovery in real time. To achieve this, Guan and his colleagues are developing a new polymer that can be injected safely into damaged tissue. Physicians can then use electron paramagnetic resonance (EPR) implanted probes for 24/7 measurement of tissue oxygen.

“It’s currently hard to monitor tissue oxygen non-invasively,” Guan said. “It requires multiple injections over a series of days of potentially toxic materials.”

The team’s technique would result in a single injection that would enable healthcare providers to assess levels over a four- to six-week period. The polymer would degrade over time, rather than lodging in the tissue.

The process is aimed primarily at ischemic diseases, ailments that result from lowered blood supply and can lead to serious damage and injury of various tissues and organs.

“The ability to monitor oxygen levels in real time would let doctors know if they need to take a more aggressive approach to treatment, or if it’s time to start tapering off treatment because the levels are approaching normal,” Guan said.

These interdisciplinary projects are conducted by collaboration with researchers from chemistry, chemical engineering, materials science and engineering, biomedical engineering, and surgery.

Most recently, Guan and colleagues at the Wexner Medical Center received roughly $1.6 million in funding to research responses to a severe arterial disease.

“Critical limb ischemia is a severe peripheral artery disease with high rates of limb loss and mortality,” Guan explained. “Currently, there is no efficient treatment available, although stem cell therapy is one of the most promising strategies.” Unfortunately, current stem cell therapy procedures suffer from inferior cell survival under the low oxygen conditions present the affected limbs.

In this project, Guan’s team will explore a new stem cell delivery system that continuously releases appropriate concentrations of oxygen to improve stem cell survival, resulting in faster vascular and muscle regeneration.

On the horizon

In addition to his funded research for the National Institutes of Health, Guan has undertaken work under the sponsorship of the National Science Foundation. He and colleagues at the Ohio State College of Dentistry are exploring ways to foster tissue regeneration.

In the field of tissue engineering, scaffolds, typically made of biomaterials, offer structural support for cells to attach themselves to one another, permitting further tissue development. They can induce tissue repair by undamaged cells at the site of an injury or disease.

“It’s challenging to design scaffolds that induce regeneration of tissues with inherently low regenerative potential, like periodontal and musculoskeletal tissues,” Guan said. He and his team will try and design scaffolds that address these challenges and offer new therapies for patients with gum and tooth issues.

Their studies will provide a fundamental understanding of the physical and biological properties of scaffolds on recruiting several cell types simultaneously and directing them to regenerate into targeted tissues. In turn, this will guide the development for scaffolds for simultaneous regeneration of multiple tissue structures.

Wound care is a major challenge to public health, ever more so thanks to increasing health care costs, an aging population, and a sharp rise in the incidence of diseases like diabetes and obesity. A team of researchers at Ohio State is examining a protein that could help close chronic wounds.

Guan and Jianjie Ma, professor of surgery, have received a $2.4 million grant from the National Institutes of Health to study this protein, MG53, and its role as an essential component of the repair machinery of our cellular membranes.

“The goal of this project is to test the hypothesis that MG53 facilities the healing of chronic wounds by enhancing cell membrane repair and epithelial stem cell function, and that hydrogel formulation of the protein represents an efficient means for dermal wound healing,” Guan said.

 

Tags: Research