By Lindsey Doermann
December 6, 2019
How visionary chemical engineers at the UW set the stage for decades of biomaterials innovation
The history of the field has seemingly little to do with the life-saving technologies of modern medicine. The origin story of biomaterials involves parachutes, repurposed car parts, and the Atomic Energy Commission. In the present day, the landscape is comprised of molecules called zwitterions, materials governed by Boolean logic, chemical ‘light sabers,’ and other science fiction-like concepts.
One can’t explain how we got from the just-make-do approach to biomaterials — using parachute cloth for blood vessel replacements, for example — to today’s precision engineering without talking about some visionary chemical engineers at the University of Washington. UW has had a long history of leadership in biomaterials. And today, ChemE researchers continue to generate new ideas and innovations at the leading edge of the field.
It’s tough to pinpoint when the term ‘biomaterials’ first appeared, says self-made biomaterials historian Buddy Ratner. But the concept has existed as long as physicians have needed substances — be they natural or synthetic, organic or inorganic — and devices that work harmoniously with the body.
An early victory for biocompatibility was the first successful kidney dialysis treatment, post-WWII. With a dialysis machine that utilized cellophane and a water pump from a Ford automobile, Dutch physician Willem Kolff revived a comatose woman, who went on to live for seven more years.
Engineers and physicians at the UW later picked up on this proof of concept. In the early 1960s, nephrologist Belding Scribner was working on hemodialysis as a treatment for acute kidney failure. Wells Moulton connected Scribner with fellow chemical engineer Albert “Les” Babb because of his expertise in mass transfer. Babb, Scribner, and bioengineer Wayne Quinton iterated on devices until they achieved the first portable dialysis machine, thereby ending the era of restrictive, hospital-based treatment.
“Those guys made the major breakthrough,” says Ratner, a ChemE and bioengineering professor. Though, as Ratner may know better than anyone, they would’ve been mistaken if they thought the problem was solved. But let’s not get ahead of ourselves.
In 1970, chemical engineer Allan Hoffman came to the UW to join the Center for Bioengineering and the Department of Chemical Engineering. Here, he started the first biomaterials group on campus and one of only a handful in the world at the time. (Today, by Ratner’s running list, there are upwards of 40 faculty at UW alone that either make or heavily use biomaterials.)
Ratner joined Hoffman’s group as a polymer scientist in 1972, fresh from his Ph.D. work on kidney dialysis membranes. He began research on hydrogels, a mainstay in today’s field but new at the time. Hoffman also recruited now-Professor Emeritus Tom Horbett to this early group.
In collaboration with physicians, the group moved the needle toward deliberate design of materials for medical devices and drug delivery. “I think we [at the UW] are pioneers in getting engineers and chemists to talk to clinical researchers,” says ChemE professor Cole DeForest. It’s now common practice, he says, but he attributes the shift in part to people such as Hoffman and Ratner.
Over time, it’s become clear that applying the chemical engineering mindset to problems in biology and medicine has been key to better materials and devices. With nonfouling surfaces, for example, Hoffman figured out how to graft hydrogels onto surfaces such as tubing (using a radiation grafter borrowed from the fisheries department, as it so happens). Then, with a hematologist and a ChemE graduate student, he studied the kinetics of platelets interacting with those surfaces and found a counterintuitive, yet consequential, relationship between hydrogel water content and platelet destruction.
The group advanced their surface science work in this period with funding from an unlikely source: the Atomic Energy Commission. The AEC fostered peacetime applications of nuclear science (and was abolished in 1974). One such idea was a plutonium 238-powered artificial heart. The AEC funded Westinghouse to develop the device and the UW team to work on the surface materials that would contact blood. Not surprisingly, that particular device didn’t gain traction, but the project kept the group moving forward. Ratner has held onto binders of their monthly reports to the agency as relics of an odd era in U.S. government R&D.
The quest for nonfouling surfaces remains central to the field. Shaoyi Jiang, who joined the ChemE faculty in 2000, brought “incredible energy” to this work, says Ratner, and has consistently driven innovation in biocompatible materials. In what Ratner calls the culmination of 18 years of work, he and Jiang developed and successfully demonstrated an ideal substance that proteins don’t stick to — and hence remains invisible to the body. Their findings resulted in a 2014 Nature Biotechnology paper.
Current ChemE faculty have advanced other ideas from the original group, such as materials that respond to specific chemical conditions. In 1983, Ratner and Horbett reported the development of a responsive material that delivered a drug based on a stimulus. In this case, it was a hydrogel — call it a “smart” material — that released insulin in response to glucose. Now, says Ratner, “Cole has come along and made smarter materials.”
Indeed, DeForest is developing materials that respond to well-defined combinations of chemical cues, “adding another level of programmability,” he says. His group recently garnered attention when they showed they could control the release of different therapeutics from a hydrogel by applying Boolean logic. They exposed their material to one or two-input combinations of enzymes, reductants, and light, and triggered the release of bioactive proteins through “yes/or/and” control.
Looking ahead in other avenues of research, DeForest is excited about taking a protein engineering approach to biomaterials synthesis, as an alternative to more-common synthetic chemistry methods. He also aims to expand his work on synthetic capillaries, which are not only critical in tissue engineering but can also serve as novel tools for basic research.
Despite such modern developments in the field, it can be hard to fathom that dialysis has remained fundamentally unchanged since its early successes. Quality of life and outcomes for people receiving dialysis treatment remain shockingly poor, with patient life expectancies hovering at 3–5 years.
These factors contributed to Ratner and nephrologist Jonathan Himmelfarb establishing the Center for Dialysis Innovation (CDI) at UW in 2016. Continuing a familiar theme in biomaterials development, the center brings together engineers and medical researchers to develop novel solutions that both improve dialysis therapy and give patients more autonomy.
Its research involves several ChemE faculty who work on the molecular-level and electrochemical aspects of dialysis, including Jiang, Jim Pfaendtner, and Eric Stuve. In one line of inquiry, for example, Pfaendtner is using molecular simulation to understand how toxins besides urea are bound up in the blood — and consequently how dialysis could remove them.
The CDI’s goals are lofty, given the problems with dialysis that have persisted for decades. With how the biomaterials field has advanced on the UW campus, though, there’s good reason to hope that the time and place are right for serious innovation.
Header image: Illustration from the December 2018 cover of Advanced Biosystems, representing Cyclic Stiffness Modulation of Cell-Laden Protein-Polymer Hydrogels in Response to User-Specified Stimuli including Light.