Abstract
Summary 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 function is 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.
Highlights
Implantable medical devices are limited by the foreign body response to the biomaterials from which they are made.[1,2,3] This response can lead to chronic inflammation, tissue damage, and fibrosis, resulting in device rejection and failure.[4,5] Macrophages are equipped with a plethora of receptors that enable them to monitor subtle changes in their microenvironment
High-Throughput Polymer Chemistry Screening Identifies Immunomodulatory Materials Using a high-throughput screening strategy, we investigated the effect of a combinatorial library of polymers on macrophage attachment, morphology, and phenotype over a 6-day culture.[17,18,19]
Monocytes from three different healthy donors were cultured on the first-generation array composed of three replicates of 141 uniqueacrylate andacrylamide homopolymers intended to screen a broad range of chemistries (Table S1)
Summary
Implanted medical devices often elicit adverse foreign body responses whereby macrophages play a central role. 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 highthroughput polymer microarray screening of diverse (meth)acrylate and (meth)acrylamide libraries. 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 M2like response. Such simple polymers are readily translatable into immune-instructive biomaterials for application in the medical device and regenerative medicine fields
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