Katie Hogan, PhD Candidate, Bioengineer at Rice University, talks about how researchers are working in the lab to grow new muscles and give reconstructive surgery patients new hope.
Interview conducted by Ivanhoe Broadcast News in May 2022.
MUSCLE INJURIES, MUSCLE LOSS, IT’S A HUGE PROBLEM AND DEBILITATING PROBLEM FOR MILLIONS OF PEOPLE. HOW ARE YOU TRYING TO FIGURE THIS ALL OUT? WHAT ARE YOU BUILDING?
KATIE HOGAN: We’re specifically using this decellularized skeletal muscle as the basis for our materials.
WHAT DOES THAT MEAN?
KATIE HOGAN: Decellularized skeletal muscle is basically we take muscle in this case from a rabbit and we’re removing the cellular components of it to leave us with just the, like, structural proteins and other molecules that are going to be tissue specific for muscle.
YOU CAN CREATE MUSCLE FROM THAT?
KATIE HOGAN: In tissue engineering, a lot of times people like to use synthetic materials. You have a lot of control over them, but materials like this retain so many of the biochemical elements that we’re not able to recapitulate yet, that they’re more efficient and effective at tissue regeneration.
SO BEFORE, FOR THE MUSCLES THAT YOU’RE DEVELOPING, THE MUSCLES THEY WOULD NEED REPLACED LIKE THE ENGINEERED ONES THEY MIGHT NEED – DO THEY LAST SO LONG? THEY DON’T GIVE YOUR BODY WHAT THEY NEED? IT’S MORE LIKE A FOREIGN BODY IN YOUR BODY?
KATIE HOGAN: Yeah. So currently clinically the major therapy is using a muscle flap from another area of your body and implanting it there, and that can have some structural restoration. It’s better aesthetically, but it’s been shown to not actually be very efficient functionally. Our goal here is to not just create new tissue, but to create new functional tissue.
SO HOW DO YOU CREATE THESE TISSUES?
KATIE HOGAN: We take a skeletal muscle from a rabbit. We use several different processes, enzymes, detergents, that kind of thing, to remove key elements that we know need to be removed and maintain the proteins that we want.
DOES THAT HAPPEN IN THE MACHINE DOWNSTAIRS THAT YOU JUST SHOWED US?
KATIE HOGAN: No. It takes place over several days, and then once we have that material, we can grind it down and use electro spinning to create our actual meshes that we would implant. For electro spinning, we take our material and we put it into a conductive solvent. We use an electric charge to create microfibers that we can then collect in different orientations to help us kind of mimic the structure of the tissue that we’re looking to regenerate.
ONCE THAT YOU PUT THIS LIKE SCAFFOLDING IN THE BODY, DOES IT JUST TAKE AND THEN GROW ITSELF AND THEN YOU NEVER HAVE TO?
KATIE HOGAN: Yeah. So that’s the idea is that we would be able to implant this mesh directly because it already has the proteins and biochemical cues that we would find in muscle. It should ideally recruit cells from your body to help come in and fill that gap and to form new muscle fibers.
NOW, WHEN YOU’RE TALKING ABOUT THE MESH, IS THERE A SIZE OR DOES THAT DEPEND ON THE AREA THAT YOU’RE WORKING ON OR?
KATIE HOGAN: So that would depend on what kind of a defect we are working with.
HOW FAST IS THIS GROWTH?
KATIE HOGAN: We recently just published another paper looking at this material in a rat model, and we looked at the tissue in growth and new muscle formation over eight weeks. At eight weeks, we were able to see like substantial new muscle fiber formation in the defect that included our material versus an injury that was just allowed to heal on its own. It should ideally be effective over the course of a couple of months to help regenerate structure and ideally function.
WHAT KIND OF INJURIES WOULD THIS BE USED FOR?
KATIE HOGAN: This would be used for those injuries where the natural capacity of skeletal muscle to regenerate itself has been overcome. I’s going to be large chunks of muscle, like 20 percent of an individual muscle gone. Clinically, we usually see that with trauma that occurs because of, like, car accidents, sports injuries, military injuries, and then also in cancer when there’s tumor removal or ablation, that needs to take a lot of the surrounding material with it.
RIGHT NOW, WHEN THERE’S AN INJURY LIKE THAT, WHAT’S DONE?
KATIE HOGAN: Right now, the best current therapy is going to be a muscle flap implantation. So, they would take a chunk of muscle from elsewhere in a patient’s body and implant it into that defect, and it can kind of fill in the gap structurally. Functionally, it’s not very effective. So, they don’t recover the additional function of that muscle.
YOU KNOW, IT’S CALLED BIOACTIVE SCAFFOLDS.
KATIE HOGAN: Yes.
CAN YOU EVEN JUST EXPLAIN TO PEOPLE WHAT THAT MEANS, THE WHOLE BIOACTIVE SCAFFOLDS?
KATIE HOGAN: So bioactive is a pretty general term, but it means that it’s going to induce a biological response when it’s implanted. In this case, because it’s made up of all the proteins and everything that we find in skeletal muscle, it will naturally interact with your body. It will convey signals to your body that will create a response and ideally a controllable response.
WILL THIS EVER BE DONE WITHOUT THE USE OF ANIMAL MODELS, BUT WOULD YOU TAKE WHAT YOU NEED FROM THE PERSON?
KATIE HOGAN: So, there’s some thought that we could use cadaveric tissues and try to create these scaffolds on a larger scale for patients without some of the tissue morbidity that we can see when we take muscle from one place and implant it into another. So ideally, that would be the eventual way to approach this.
IN THE RESEARCH WITH THE ANIMALS, CAN YOU TELL ME WHAT YOU FOUND WITH THAT IN A LITTLE BIT MORE DETAIL?
KATIE HOGAN: Yeah, absolutely. We’re using a rat model. We created an injury in the leg, in the tibialis anterior muscle, and we removed about 20 percent of that muscle by weight. And we implanted some of our scaffolds stacked on top of each other. At the end of eight weeks, what we found was that compared to an empty defect where we didn’t implant anything, these decellularized ECM scaffolds were able to induce new myotube formation, new myofiber formation in that defect as well as increase like new vessel formation in that defect to support new tissue growth. So that’s kind of the biggest findings that we had.
HAS GROWING MUSCLES EVER BEEN DONE BEFORE?
KATIE HOGAN: Not using these types of materials to this extent. So, this material and methodology is, I think, pretty unique to our lab because normally people have to combine this decellularized skeletal muscle with other polymers or materials to create new structures, whereas we’re able to just take skeletal muscle itself and create this material. So, it’s fairly unique in that way.
WHAT HAPPENS TO THE SCAFFOLDING AFTER THE MUSCLES HAVE?
KATIE HOGAN: So, because it’s made up of stuff that’s native to the body, it should be degraded by the body over time. Ideally, it’s being degraded along this – like, as new tissue is being formed, the scaffold is being degraded, and the new tissue is able to take its place.
WHAT’S NEXT FOR ALL OF THIS?
KATIE HOGAN: Since we just finished up our first round of animal studies, I guess the next step would be to repeat this study in animals and then look at functional data, so being able to see how well the muscles are contracting after new tissue has formed in that defect.
CAN YOU GIVE ME A BRIEF DESCRIPTION OF ELECTRO SPINNING?
KATIE HOGAN: It’s a lot of words. Electro spinning is where we can take material, usually a polymer. In this case our skeletal muscle, we put it into a conductive solvent. We can extrude it from a needle, and there’s an electric field between the needle and a plate and that electric field will draw out our material as like a microfiber which is then deposited onto the plate. We can collect it there and we can use different collection devices to help us change the orientation of the fibers that we’ve collected. Ideally, we’d be able to use like large quantities of material and create like large sheets of this material that we can then like stack on top of each other to create a thickness that is relevant for a muscle defect in a person. We’ve used smaller electro spinning setups that allow us to create kind of smaller meshes, those are the ones that we’ve used in our studies.
END OF INTERVIEW
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