Altered Macrophage Behavior Can Accelerate Wound Healing
Macrophages of the innate immune system exhibit a range of different states known as polarizations. M1 macrophages are inflammatory and focused on attacking pathogens and errant cells. M2 macrophages are anti-inflammatory and focused on tissue maintenance, playing an important role in regeneration from injury. Not a vital role, strictly speaking, as wounds still heal in the absence of macrophages, but the presence of macrophages in the M2 polarization accelerates the process. As researchers demonstrate here, ways to guide macrophages into the desired pro-regenerative M2 state can further speed wound healing.
Macrophages play a key role in wound healing. Dysfunction of their transition from the M0 unpolarized state to the M2 polarization leads to disorders of the wound immune microenvironment and chronic inflammation, which affects wound healing. Regulating the polarization of M0 macrophages to M2 macrophages is an effective strategy for treating wound healing. Mesenchymal stem cells (MSCs) deliver endogenous regulatory factors via paracrine extracellular vesicles, which may play a key role in wound healing, and previous studies have shown that apoptotic bodies (ABs) are closely associated with inflammation regression and macrophage polarization. However, the specific regulatory mechanisms involved in ABs remain unknown.
In the present study, we designed an MSC-AB (MSC-derived AB)-loaded polycaprolactone (PCL) scaffold, evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro, and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing. Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs, and drives M0 macrophages to program M2 macrophages to regulate inflammation and angiogenesis, thereby synergistically promoting wound healing. This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immune responses.