Immunology and insider dealing: How macrophages trick your body into accepting biomaterials

Author: Holly Wobma, 03/18/14

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I’d like to make an unusual proposition. It’s occurred to me that our bodies are kind of snobs.

Macrophages (from the Greek meaning "big eater") are known for the work in attacking foreign substances in the body. But new research is showing that it's as much about what they accept as what they deny. Stock photo.

Macrophages (from the Greek meaning “big eater”) are known for attacking foreign substances in the body. But new research is showing that it’s as much about what they accept as what they deny — and how they work together. Stock photo.

Personality aside, our bodies are extremely particular. They reject tons of bacteria and viruses, while accepting others. They reject foreign tissues but can sometimes be coaxed into accepting them when bribed with medications. I suppose you could simply call it evolution, but figuring out who makes it into the elitist club that is our bodies is, nevertheless, one of the fundamental challenges of tissue engineering and transplant science.

As I’ve commented at length before, for an engineered graft to be usefully incorporated, it must 1) not be attacked by the immune system and 2) be successfully vascularized. These same principles apply toward the field of biomaterials, where non-cellular grafts are implanted into the body at the hopes that they will become cellularized, remodeled, and integrated with the body as a whole.

If you think about it, for a synthetic material to become part of a person, it must have pretty good connections pulling some strings.

For this reason, I am incredibly impressed with a paper in this month’s issue of Biomaterials. In it, Dr. Kara Spiller, currently an assistant professor at Drexel University, helps delineate the string of signals that leads to angiogenesis (i.e. new blood vessel growth) and vascularization of collagen scaffolds. Her paper specifically focuses on macrophages, a cell type that seems to carry a lot of weight in terms of the vascularization process.

It turns out that when a synthetic graft is implanted, it stimulates an inflammatory response, which involves several different types of macrophages (M1, M2a, M2c etc.). Traditionally, it has been thought that only certain subtypes of these macrophages have been influential in terms of promoting angiogenesis; however, their precise roles have been poorly understood. Dr. Spiller’s work abolishes the idea that it is only one specific macrophage type that is pro-angiogenic, and instead demonstrates that all have a unique message, which when timed properly, leads to vascularization of implanted biomaterials.

By better understanding what defines the different subsets of macrophages and which proteins they release to spread their message, we may be able to better control a patient’s response to a biomaterial-based graft in the clinic, as well as the development of vascularized tissue-engineered grafts in the lab. “The more we learn about macrophages, the more we realize that they’re at the centre of everything — from repair to regeneration to disease,” says Dr. Spiller. “If we can control their behavior, we can potentially control everything else.” Either way, macrophage biology is becoming a hot topic in numerous fields including wound healing, obesity, autoimmune diseases, and cancer.

While inclusion criteria for our bodies may always remain slightly elusive, it is clear that the different macrophages deal with each other, behind the scenes, to lobby for grafts to be accepted.

Research cited:
Spiller K.L., Anfang R.R., Spiller K.J., Ng J., Nakazawa K.R., Daulton J.W. & Vunjak-Novakovic G. (2014). The role of macrophage phenotype in vascularization of tissue engineering scaffolds, Biomaterials, DOI:
Mirza R.E., Fang M.M., Weinheimer-Haus E.M., Ennis W.J. & Koh T.J. (2014). Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice, Diabetes, 63 (3) 1103-1114. DOI:
Amano S., Cohen J., Vangala P., Tencerova M., Nicoloro S., Yawe J., Shen Y., Czech M. & Aouadi M. (2014). Local Proliferation of Macrophages Contributes to Obesity-Associated Adipose Tissue Inflammation, Cell Metabolism, 19 (1) 162-171. DOI:
King R.L. & Weiss M.J. (2014). Iron-laden macrophage in autoimmune disease, Blood, 123 (4) 469-469. DOI:
Comito G., Giannoni E., Segura C.P., Barcellos-de-Souza P., Raspollini M.R., Baroni G., Lanciotti M., Serni S. & Chiarugi P. (2013). Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression, Oncogene, DOI:

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Holly Wobma

Holly Wobma

MD/PhD student at Columbia University
Holly is an MD-PhD student at Columbia University in New York. She recently (2011) completed a Bachelor of Health Sciences Honours Degree from the University of Calgary, where she pursued research related to nanotechnology and regenerative medicine. In addition to research, she enjoys participating in science outreach roles. Previously, she contributed to an award-winning Nanoscience animation produced by the Science Alberta Foundation (“Do You Know What Nano Means?”), and served on the board of directors for the Canadian Institute for Photonic Innovations Student Network. Holly's lab tweets @GVNlab.
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