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Thus, it is necessary to fully explore how macrophages interact with dynamic ECM remodeling to modulate endogenous tissue repair progress. Thus, there is a need for robust immunomodulatory strategies that can control macrophage polarization for tuning inflammatory responses that can promote tissue repair.Īlthough many soluble cytokine factors have been reported to be potential immunomodulation targets that dictate macrophage crosstalk, the cell-ECM interactions have an underappreciated regulatory role in macrophage inflammation. Determining how the microenvironment triggers a phenotypic switch to either a ‘pro-inflammatory (M1)’ or an ‘anti-inflammatory (M2)’ macrophage phenotype is critical to expanding tissue destruction or orchestrating repair. Inflammation, predominantly facilitated by macrophages, coincides with dynamic extracellular matrix (ECM) remodeling to influence tissue plasticity in disease and repair. Altogether, we highlight an emerging use of biomimetic, photo-responsive, and bioactive HA-APP nanocomposite hydrogel to command 3-D cell-ECM interactions for modulating macrophage polarization, which may shed light on cell-ECM interactions in innate immunity and inspire new biomaterials-based immunomodulatory therapies. We demonstrate that photo-controlled 3-D ECM-RGD peptide conjugation can activate αvβ3 integrin of macrophages, and periodic αvβ3 integrin activation can enhance anti-inflammatory M2 macrophage polarization. We exploited photo-degradative APP (alkoxylphenacyl-based polycarbonate) nanocomposites to permit user-controlled RGD (Arg-Gly-Asp) adhesive peptide release and conjugation to a HA-based extracellular matrix (ECM) for real-time integrin activation of macrophages encapsulated in 3-D HA-APP nanocomposite hydrogels. In this work, we engineered a biomimetic and photoresponsive hyaluronan (HA) hydrogel nanocomposite with tunable 3-D ECM adhesion sites for dynamic macrophage immunomodulation.
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Thus, engineering an immunomodulatory biomaterial has significant implications for resolving inflammation.
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Macrophages are a predominant immune cell population that drive inflammatory responses and exhibit transitions in phenotype and function during tissue remodeling in disease and repair.