Hydrogel crosslinking modulates macrophages, fibroblasts, and their communication, during wound healing.

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels.

IL-17 Control of Cutaneous Immune Homeostasis.

IL-17 is widely recognized for its roles in host defense and inflammatory disorders. However, it has become clear that IL-17 is also an essential regulator of barrier tissue physiology. Steady-state microbe sensing at the skin surface induces low-level IL-17 expression that enhances epithelial integrity and resists pathogens without causing overt inflammation.

Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing.

Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses.

Extracellular Matrix-Based Strategies for Immunomodulatory Biomaterials Engineering.

The extracellular matrix (ECM) is a complex and dynamic structural scaffold for cells within tissues and plays an important role in regulating cell function. Recently it has become appreciated that the ECM contains bioactive motifs that can directly modulate immune responses. This review describes strategies for engineering immunomodulatory biomaterials that utilize natural ECM-derived molecules and have the potential to harness the immune system for applications ranging from tissue regeneration to drug delivery.

Harnessing macrophage plasticity for tissue regeneration.

Macrophages are versatile and plastic effector cells of the immune system, and contribute to diverse immune functions including pathogen or apoptotic cell removal, inflammatory activation and resolution, and tissue healing. Macrophages function as signaling regulators and amplifiers, and influencing their activity is a powerful approach for controlling inflammation or inducing a wound-healing response in regenerative medicine. This review discusses biomaterials-based approaches for altering macrophage activity, approaches for targeting drugs to macrophages, and approaches for delivering macrophages themselves as a therapeutic intervention.