Integrin‐Mediated Interactions Control Macrophage Polarization in 3D Hydrogels. Issue 21 (7th August 2017)

• Record Type: Journal Article
• Authors: Cha, Byung‐Hyun; Shin, Su Ryon; Leijten, Jeroen; Li, Yi‐Chen; Singh, Sonali; Liu, Julie C.; Annabi, Nasim; Abdi, Reza; Dokmeci, Mehmet R.; Vrana, Nihal Engin; Ghaemmaghami, Amir M.; Khademhosseini, Ali
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 21(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-08-07
• Subjects: hydrogels -- immune modulation -- integrin -- M1 -- M2 -- macrophage polarization; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201700289
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin‐mediated interactions between human monocytic THP‐1 cells and collagen‐derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP‐1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin‐4 (IL‐4) induce an anti‐inflammatory M2‐like phenotype and propagate the effect of IL‐4 in induction of M2‐like macrophages. Importantly, integrin α2β1 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL‐4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin‐mediated 3D microenvironment for biomaterial‐based programming. Abstract : Macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. However, active control over macrophage polarity has remained elusive. This study reveals that biomaterial‐based integrin attachment can steer human monocytic cells differentiation into a specific macrophage lineage and thus has broad clinical implications.