Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo
Creators
- Rostam, Hassan M.
- Fisher, Leanne E.
- Hook, Andrew L.
- Burroughs, Laurence
- Luckett, Jeni C.
- Figueredo, Grazziela P.
- Mbadugha, Chidimma
- Teo, Alvin C.K.
- Latif, Arsalan
- Kämmerling, Lisa
- Day, Mitchell
- Lawler, Karen
- Barrett, David
- Elsheikh, Somaia
- Ilyas, Mohammad
- Winkler, David A.
- Alexander, Morgan R.
- Ghaemmaghami, Amir M.
Description
Implanted medical devices often elicit adverse foreign body responses whereby macrophages play a central role. Here, we identify simple polymers that instruct different immunological responses by modulating macrophage attachment and polarization to pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotypes. These immune-instructive polymers were discovered using in vitro high-throughput polymer microarray screening of diverse (meth)acrylate and (meth)acrylamide libraries. The bioinstructive polymer functionis validated in vivo within a murine foreign body model. Differential tissue response from polymers coated on silicone tubing is consistent with in vitro macrophage pro- and anti-inflammatory responses. Polymer structure-cell response relationships are modeled using machine learning to reveal molecular descriptors useful for describing immune-instructive polymers. Analysis of the protein layer adsorbed to polymers from media suggests that thicker layers may relate to M1-like phenotype whereas the reverse relates to M2-like response. Such simple polymers are readily translatable into immune-instructive biomaterials for application in the medical device and regenerative medicine fields.
Files
UNOT_Immune-Instructive Polymers ControlMacrophage Phenotype and Modulate theForeign Body ResponseIn Vivo.pdf
Files
(3.7 MB)
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