Macrophages in Healing Wounds: Paradoxes and Paradigms

DiPietro, Luisa A.; Wilgus, Traci A.; Koh, Timothy J.

doi:10.3390/ijms22020950

Cited by 54 publications

(42 citation statements)

References 89 publications

(109 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, we observed varying PBM doses evoked discrete functional cellular responses in keratinocyte, fibroblasts and macrophage responses suggesting further improvements to both dose and timing of PBM protocols are feasible for specific wound phase management. A particular area of future investigation would focus on the macrophage subtypes (M1 versus M2) that have been demonstrated to be modulated by PBM treatments and are well known to contribute to the healing responses 81 , 82 . Evidences for TGF-β signaling in later healing stages could be attributed to the endogenous autocrine signaling.…”

Section: Discussionmentioning

confidence: 99%

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1

Khan

Rahman

Tang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-β1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-β signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-β dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-β1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-β1/β3 knock-in (TGF-β1Lβ3/Lβ3) mice. PBM treatments failed to activate the chimeric TGF-β1Lβ3/Lβ3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-β1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1

Khan

Rahman

Tang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Their phenotype readily changes according to spatiotemporal cues during repair ( 21 ). Many functional attributes ascribed to macrophages are found in skin wound models, such as scavenging, phagocytosis and antigen presentation in inflammatory phase ( 22 ), stem cell recruitment and revascularization in proliferative phase ( 23 ), and extracellular signaling transduction in remodeling phase, owing to their plasticity and heterogeneity ( 24 ). Recently, particular attention has been paid to their resolution of inflammation and shift toward regeneration ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Macrophage Related Chronic Inflammation in Non-Healing Wounds

et al. 2021

View full text Add to dashboard Cite

Persistent hyper-inflammation is a distinguishing pathophysiological characteristic of chronic wounds, and macrophage malfunction is considered as a major contributor thereof. In this review, we describe the origin and heterogeneity of macrophages during wound healing, and compare macrophage function in healing and non-healing wounds. We consider extrinsic and intrinsic factors driving wound macrophage dysregulation, and review systemic and topical therapeutic approaches for the restoration of macrophage response. Multidimensional analysis is highlighted through the integration of various high-throughput technologies, used to assess the diversity and activation states as well as cellular communication of macrophages in healing and non-healing wound. This research fills the gaps in current literature and provides the promising therapeutic interventions for chronic wounds.

show abstract

“…However, a strong shift from a pro- to an anti-inflammatory phenotype also undermines the M1-M2 balance. Excessive activity of M2 macrophages during wound healing has been related to the formation of hypertrophic scars [ 125 ]. M2 macrophages contribute to scar formation by increasing the synthesis of the ECM proteins as well as secreting MMP-10 and TGF-β1 [ 126 ].…”

Section: Chronic Wound Healingmentioning

confidence: 99%

“…The modification of macrophage phenotype may become a promising therapeutic approach to treat chronic skin inflammation [ 125 ]. Phosphatidylserine-containing liposomes (PSLs) were shown to induce the polarization of macrophages towards M2 phenotype in mice with pressure ulcers (PU).…”

Section: Modulation Of the Immune System To Improve Wound Healingmentioning

confidence: 99%

Immunology of Acute and Chronic Wound Healing

et al. 2021

View full text Add to dashboard Cite

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

show abstract

Macrophages in Healing Wounds: Paradoxes and Paradigms

Cited by 54 publications

References 89 publications

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1

Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1

Macrophage Related Chronic Inflammation in Non-Healing Wounds

Immunology of Acute and Chronic Wound Healing

Contact Info

Product

Resources

About