@Elutia
Humanizing Medicine
www.elutia.com
Unlocking Macrophage Mysteries with Dr. Stephen Badylak on Biologic Scaffold Materials and Immune Responses (M1/M2)
In the late nineties, the immunologists discovered that all macrophages don't do the same thing and they started asking the question, why do you have tumors surrounded by loads of these cells and the tumors grow? They discovered that even though they all look alike, there's different phenotypes of them or different flavors of macrophages. They range from what I just described as a pro-inflammatory macrophage, sometimes called M1 or macrophage 1, to the opposite extreme, which is M2, which does exactly the opposite. It suppresses inflammation by changing the types of what we call cytokines, and chemokines, and molecules that are released from the macrophage. Instead of destroying things, it actually rebuilds them. It sends signals out to other cells to, all right, settle down the inflammation. Now it's time to resolve the problem that's there. In addition to the recruitment of stem and progenitor cells, to get the right cells at the site of interest, the signaling molecules that are released from the ECM (extracellular matrix), they regulate or orchestrate this change from M1 to M2.
So, this really sets these biologic scaffold materials apart from other materials because they don't have such signaling molecules. In fact, we've looked at just about every biomaterial that is used in medicine today. Any synthetic biomaterial, every single synthetic material we've ever looked at, whether it's degradable or non-degradable, promotes an M1 pro-inflammatory response. The only ones that facilitate this M1 to M2 switch are the degradable matrix materials. There are also naturally occurring antimicrobial peptides present in the extracellular matrix all over the body. It's one of the very first things that happens when we have an injury. The matrix gets injured, releases this first line of defense. They're present in all tissues and they always respond to injury, but these extracellular matrix molecules get released during degradation actually up-regulate the production of antimicrobial peptides by the macrophages that come in. So, in the synthetic materials, particularly the non-degradable materials, you will end up with a layer of connective tissue, typically scar tissue around the implant.
That type of tissue is usually not very vascular after the first couple of weeks to months, and so one of the potential problems with the synthetic materials is if they get infected, it's a big problem because it's almost impossible to completely eliminate all the bacteria on an infected synthetic implant and oftentimes results in it just has to be explanted and you start over. With a biologic material, since it stimulates things like new blood vessels to grow into it, you've got a lot of the body's own cells there. It handles exposure to contaminants like bacteria and such, like any tissue in the body. It fights it off when it can and typically does. So, let's think about how a biologic scaffold material like ECM responds to a contaminant. We talked about the antimicrobial peptides that are resident in the extracellular matrix and sort of do the immediate job.
Well, they get used up pretty quickly. The second thing that happens is the other signaling molecules in the matrix turn cells like macrophages on to produce increased amounts of new antimicrobial peptides. The third way, it's vascularized. The extracellular matrix recruits new blood vessels in the process of remodeling that we were talking about and what you really want in any contaminated site or any site where there's healing, is a rich blood supply because now you can bring the body's entire resources to fight off infection. New blood cells coming out of the circulation, if it's there long enough, even antibodies could get formed and had the adaptive component of the immune system also involved. So, there's a lot of advantages to basically using what Mother Nature has built into ECM.
Elutia™ BioEnvelopes, created from an extracellular matrix (ECM), are intended to securely hold a cardiac implantable electronic device or an implantable neurostimulator to create a stable environment when implanted in the body. The views and ideas presented in this video are solely those of the speaker, and the content is not intended to serve as medical advice. Elutia does not practice medicine. Practitioners should refer to the full indications for use and operating instructions of any products referenced herein before prescribing them.
Learn more:
www.elutia.com
Phone: 470-514-4085
Customer Service: 877-651-2628
MK-1821-01A