Plenary Pioneers, Part I: When Engineering and Endocrinology Meet

At ENDO 2021, the first time the Endocrine Society’s annual conference has gone all-virtual, a live Presidential Plenary on March 20 will feature a pair of presentations on the latest developments in basic tissue engineering. Endocrine News speaks with Andrés J. Garcia, PhD, about his session, “Synthetic Hydrogels as Engineered Niches in Regenerative Medicine.”

 

Taking place March 20–23, 2021, ENDO 2021 offers more than 70 live sessions in addition to another 70 on demand via a state-of-the-art digital platform that also accommodates interactivity among participants and networking opportunities.

One live session you won’t want to miss is “The Impact of Basic Tissue Engineering and the Basic Biology of GPCRs in Emerging Therapies,” a presidential plenary on March 20, from 11:00 am to 12:00 pm.

Comprising two talks, this plenary showcases pioneering advances in therapy with “Synthetic Hydrogels as Engineered Niches in Regenerative Medicine,” by Andrés J. García, PhD, executive director, Parker H. Petit Institute for Bioengineering and Bioscience and George W. Woodruff School of Mechanical Engineering Regents’ Professor at the Georgia Institute of Technology in Atlanta, Ga., and “Structural Insights into G Protein-Coupled Receptor Activation: Implications for Drug Discovery,” by Brian Kobilka, MD, professor and chair of molecular and cellular physiology at the Stanford University School of Medicine, Stanford, Calif., and co-recipient of the 2012 Nobel Prize in Chemistry for his work with GPCRs.

In part one of a two-part series of articles highlighting this plenary session, Endocrine News speaks to Garcia about his research, what it means for future therapies, and what attendees can expect from his session.

Tissue Engineering: Biomaterial Technology to Address Clinical Limitations

“My lab develops biomaterials for regenerative medicine,” says Andrés J. García, PhD. Looking forward to making his debut at an ENDO conference, he explains that his work as an engineer intersects with the field of endocrinology in designing materials that can be delivered to the body for tissue repair.

“I will present our work with synthetic hydrogels, which are fully defined, cross-linked polymer networks,” he says. These very soft, gelatin-like materials are composed of about 95% water and about 5% polyethylene glycol. “We engineer the hydrogels to mimic extracellular matrices —normal materials in the body.”

“The hydrogels have generated a lot of excitement because our materials are fully defined, and they’re of a chemical synthetic nature,” García says. “So, as we move to clinical translation into humans — we’re not there, yet but we’re moving toward that — from both a regulatory standpoint and associated safety considerations as well as from the manufacturing standpoint and scalability, this synthetic nature is much preferred over extracts of human or animal cadaver origin.” –  Andrés J. García, PhD, executive director, Parker H. Petit Institute for Bioengineering and Bioscience and George W. Woodruff School of Mechanical Engineering Regents’ Professor at the Georgia Institute of Technology in Atlanta, Ga.

The artificial matrices can be designed for different applications, for example, to deliver pancreatic islets into patients with diabetes to achieve better metabolic control, or to be combined with intestinal organoids in culture for transplantation and engrafting into intestinal wounds. The potential applications are, indeed, probably limitless.

“The hydrogels have generated a lot of excitement because our materials are fully defined, and they’re of a chemical synthetic nature,” García says. “So, as we move to clinical translation into humans — we’re not there, yet but we’re moving toward that — from both a regulatory standpoint and associated safety considerations as well as from the manufacturing standpoint and scalability, this synthetic nature is much preferred over extracts of human or animal cadaver origin. Those are more variable from lot to lot and from sample to sample, whereas with the synthetic material, we know precisely how to make it and with what characteristics. We can establish very good quality control,” he continues.

As cutting-edge as this developing technology is, García likens the hydrogel material to a simple fishnet, with the ropes that make up the netting akin to the cross-linked chain of molecules of the polymer and the open space of the net akin to the interstices of the overall matrix. “Just like in a fishnet, the majority is water or open space, and the actual backbone of the fishnet takes up very little space. This is how these hydrogels look molecularly,” he explains.

Moreover, polyethylene glycol is used in other U.S. Food and Drug–approved devices. “There’s a long track record of safety using this material, and then we add functionality to it. For example, we can add adhesion peptides derived from normal matrices that the cells recognize and can adhere to. We can also add in other biological signals essentially to communicate with the cells or with the immune environment of the host,” García says.

The delivery system is as ingenious as the rest of this enterprise and itself confers special advantages. “We can put our materials in a pre-test block, and we can formulate the materials in an injectable carrier so it’s in a liquid form and injectable through a needle or a catheter. When it reaches the site that we want it to go into, it will gel into a solid and localize there. So, we have a lot of control in terms of how we make the material, what biological sequences we want to add to the material, and how the material degrades, and you cannot do this with naturally derived materials,” García says.

An Easily Tailored Blank Slate

The nature of the hydrogel as a “blank slate” that can be tailored with any number of biochemical and biophysical properties to achieve targeted functionalities as its main utility. They are also especially compatible with the microenvironment of human cells, which is also mostly water. But they can’t fix everything — at least not yet. “The limitation is that they are relatively soft. If the mechanical demands in the body are very high, these materials will not work well. We can’t use them to replace bone or cartilage in the knee, for example; this material would get destroyed,” García explains.

Nevertheless, he is not daunted. “As an engineer, I’m a problem solver and I love going to these conferences and talking to clinicians and other basic scientists to learn what problems they face, and usually together we can identify a solution or a potential way to address those problems.”

“Several of the more advanced projects are now in large animal studies and showing very positive results. One in particular will likely be a first in human study next year. There’s a lot of potential there, and we’re working through the different stages to see how it works.” – Andrés J. García, PhD, executive director, Parker H. Petit Institute for Bioengineering and Bioscience and George W. Woodruff School of Mechanical Engineering Regents’ Professor at the Georgia Institute of Technology in Atlanta, Ga.

The García Lab is not the only lab to be working with hydrogels, but they may soon be moving out of the proof-of-principle stage with some applications. “In our pipeline, several of the more advanced projects are now in large animal studies and showing very positive results. One in particular will likely be a first in human study next year. There’s a lot of potential there, and we’re working through the different stages to see how it works.”

Although the hydrogels have obvious implications for cosmetic applications (e.g., growing hair, filling in wrinkles), García and team are committed to finding solutions to address human disease.

Horvath is a freelance writer based in Baltimore, Md. In the December Endocrine News she wrote about the recommendations from Endocrine Society journal editors on what scientific discoveries of 2020 were most notable in the field of endocrinology.

Part II of the “Plenary Pioneers” series can be accessed here.