Grants and Contracts Details
Description
A bioinspired strategy to elicit transcriptional control of macrophages for bone
regeneration
Inflammation plays a vital role during bone formation, resorption, and fracture healing. The
process of fracture healing is biologically entangled with that of acute inflammation and innate
immunity. A proper sequence and dose of inflammatory signals are critical for proper bone
healing. Macrophages are one of the first cells that infiltrate the fracture site and are
indispensable for fracture healing. Macrophages are shown to promote osteoblastic
differentiation and vascularization. It is well recognized that mechanical conditions influence
callus development and the type and extend of osteogenesis during fracture. But the majority of
the work on macrophage response, in the context of fracture healing, has focused on activation
mediated by biochemical signals. The physical parameters of the fracture microenvironment,
especially matrix mechanics and their influence on macrophage immunophenotypes, are largely
overlooked.
Macrophages respond to the changes in extracellular matrix mechanics through actin-
cytoskeletal reorganization, nuclear deformation, and gene expression. We hypothesized that
the physical forces in the form of substrate mechanics can elicit transcriptional control of
macrophages via MRFT-A release (from G-actin) and HDAC3 redistribution. The two
independent goals for this project are 1) To test the hypothesis and elucidate the actin
cytoskeleton-mediated transcriptional control in macrophages during fracture in a murine model;
2) To engineer immunomodulatory materials with suitable viscoelastic mechanics to guide the
transcriptional machinery of macrophages towards therapeutic bone regeneration. The
proposed research not only provides insights into the role of the innate immune response in
fracture healing but also develops next-generation immunomodulatory materials for enhanced
bone regeneration.
Status | Finished |
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Effective start/end date | 1/1/22 → 12/31/23 |
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