Grinstaff Delivers Inaugural Charles DeLisi Lecture

in ENG Spotlight-Research, NEWS

Professor Mark Grinstaff (BME, MSE, Chemistry, MED)
Professor Mark Grinstaff (BME, MSE, Chemistry, MED)

Professor Mark Grinstaff (BME, MSE, Chemistry, MED) presented the inaugural Charles DeLisi Distinguished Lecture on April 2. The first named endowed lecture in the history of the College of Engineering, the Charles DeLisi Award and Lecture recognizes faculty members with extraordinary records of well-cited scholarship, and outstanding alumni who have invented and mentored transformative technologies that impact our quality of life.

Speaking before a packed audience of students, faculty and researchers at the Photonics Center, Grinstaff explored how over the past two decades, he, his students and collaborating researchers have translated ideas from the laboratory into highly effective new devices and materials for clinical applications.

“When I think about the problems I want to solve with my students, it’s very much about those projects that are rich in basic science and engineering, that will benefit society, and that will motivate us,” he said. He then described three such projects that have produced new biomaterials to improve diagnosis and treatment of major diseases and injuries.

 

Taking Biomaterials from Bench to Bedside

The first project resulted in a highly absorbent, biocompatible hydrogel that not only seals wounds but (unlike sutures) can later be dissolved and gently removed, thereby minimizing pain and damage to injured tissue. The sealant is administered via double-barreled syringe, with each barrel containing a different compound. Once the two compounds are pushed out of the syringe onto a surface, they combine within seconds to form a honeycomb-like network of cross-linked chemical bonds.

The resulting hydrogel absorbs fluid on the surface, has the consistency of gelatin and sticks like an adhesive, remaining intact for several days. Adding a solution of cysteine methyl ester, a derivative of a natural amino acid, to the hydrogel causes the gel’s cross-linked bonds to break apart and the gel to dissolve within several minutes. Grinstaff is now investigating this biomaterial as a pain-free pediatric burn dressing; his previous work on hydrogel adhesives led to clinically approved sealants for treating lacerations to the cornea, the spine and the dura (the outermost membrane covering the brain and spinal cord).

The second project took aim at lung cancer, the leading cause of cancer mortality in the US, and yielded a drug delivery device to prevent post-surgery recurrence of the disease.

The standard of care for early stage patients is to surgically remove, or resect, lung tissue tumors, but nearly 40 percent of patients receiving such treatment develop recurrent disease. Systematic injection of paclitaxel, the standard chemotherapy agent for lung cancer, delivers inadequate concentrations of the drug to diseased lung tissue and damaging toxins to healthy organs.

To address the problem, Grinstaff and his collaborators produced flexible, paclitaxel-loaded polymer films that allow the controlled, low-dose, targeted release of the drug over an extended period, and demonstrated their ability to prolong recurrence time after surgical resection of lung tumors in mice. Using the same polymers, they also developed a highly sensitive nanodevice to detect the presence of cancer in the lung.

The third project produced a joint lubricant that could bring longer-lasting pain relief to the more than 27 million Americans who suffer from osteoarthritis, the most common form of joint disease and a leading cause of disability in the elderly. This new synthetic polymer supplements synovial fluid, the natural lubricant in joints, and lasts about two weeks longer than the leading synovial fluid supplement. It works by reducing friction between cartilage surfaces that cushion the joint, resulting in less wear and surface-to-surface interaction.

Grinstaff and collaborators have also developed a sensitive imaging method to enhance diagnosis of osteoarthritis and enable improved care through earlier detection and more targeted treatments. Combining nanotechnology, engineering and medicine, the method exploits new, biocompatible nanoparticles and small molecules as contrast agents to image surface and interior regions of articular cartilage (the smooth, water-rich tissue that lines the ends of bones in load-bearing joints) — regions that traditional X-ray illumination cannot detect.

All projects were funded by the National Institutes of Health, National Science Foundation, Wallace H. Coulter Foundation, and other agencies. Two are now in various stages of commercialization via companies Grinstaff cofounded: HyperBranch Medical Technology, which produces biodegradable surgical sealants that are widely used by surgeons, and Acuity Bio, which is developing flexible films to prevent tumor recurrence after surgical resection. 

 

Lessons Learned

Grinstaff concluded the lecture by attributing his success in translational research to his lab group and collaborators, as well as a few key practices that have kept his projects moving forward.

“I think teams are really important; if you have the right people, you can do amazing things,” he observed. “You should be quantitative, inquisitive, and ask for help. Communication is essential. And failure is acceptable, but you should do it quickly so you can redesign your experiments, have a new hypothesis and think about new design criteria.”

The Delisi Lecture continues the College’s annual Distinguished Lecture Series, initiated in 2008, which has honored several senior faculty members. The previous recipients are Professors John Baillieul, (ME,SE), Malvin Teich (ECE) (Emeritus), Irving Bigio (BME), Theodore Moustakas (ECE, MSE),  H. Steven Colburn (BME), Thomas Bifano (ME, MSE) and Christos Cassandras (ECE, SE).

 

Efficiency of Grinstaff's hydrogel wound sealant (dyed in green) in sealing a puncture on a tissue surface, preventing leakage (a). Sealant washed off upon exposure to an amino acid solution for wound re-exposure and further treatment (b&c).
Efficiency of Grinstaff's hydrogel wound sealant (dyed in green) in sealing a puncture on a tissue surface, preventing leakage (a). Sealant washed off upon exposure to an amino acid solution for wound re-exposure and further treatment (b&c).

Polymer film on surgical collagen scaffold. Upper panel shows a dry film; lower panel shows flexibility of a wet film. Scale bar: 5 mm. Films can be used to help prevent recurrence of lung cancer after surgical resection. (Source: Annals of Surgical Oncology)
Polymer film on surgical collagen scaffold. Upper panel shows a dry film; lower panel shows flexibility of a wet film. Scale bar: 5 mm. Films can be used to help prevent recurrence of lung cancer after surgical resection. (Source: Annals of Surgical Oncology)