Preservation of Eschar Prevents Excessive Wound Healing by Reducing M2 Macrophages Polarization

Background: Removal of the eschar has gradually become a consensus on treatments of deep dermal necrosis after skin trauma in recent years, whereas exaggerated scar contracture and tissue proliferation developed during healing have received little attention. Here, the authors investigated the effects of eschar on excessive wound healing of small dermal damage and focused on the role M2 macrophages played, hoping to offer a theoretical basis to improve patients’ cosmetic satisfaction. Methods: A mouse dorsal wound model (n = 12) was established by electric heating pads heating for 20 seconds on each side of the spine, and the left side was the preserved group. Macrophage numbers, expression of wound-healing-associated proteins, and inflammatory cytokine levels were assessed at different time points by immunohistochemistry and quantitative real-time polymerase chain reaction. A co-culture system of M2 macrophages and myofibroblasts was created in vitro. Immunohistochemistry, real-time polymerase chain reaction, and Western blot were performed to evaluate the proliferation, migration, and protein expression of myofibroblasts. Results: Preserving eschar inhibited contraction-associated proteins (α-smooth muscle actin and vimentin) and collagen expression, inflammatory cytokine (IL-1β, IL-10, TFN-α, and IL-4) expression, and M2 macrophage infiltration. Mechanistically, M2 macrophages potentially contributed to excessive wound healing by promoting myofibroblasts proliferation, migration, and production of contraction-associated proteins. Conclusion: Eschar preservation in wounds could reduce inflammation and negatively modulate myofibroblasts by inhibiting M2 macrophage polarization and infiltration, preventing excessive wound contraction and collagen deposition.

[1]  P. Del Rio,et al.  Wounds morphologic assessment: application and reproducibility of a virtual measuring system, pilot study , 2021, Acta bio-medica : Atenei Parmensis.

[2]  B. Dheansa,et al.  Accuracy of virtual assessment in hand trauma , 2021, JPRAS open.

[3]  [National expert consensus of the clinical application of eschar dermabrasion in burn wounds (2021 version)]. , 2021, Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns.

[4]  Won Lee,et al.  Aspiration Revisited: Prospective Evaluation of a Physiologically Pressurized Model With Animal Correlation and Broader Applicability to Filler Complications. , 2021, Aesthetic surgery journal.

[5]  Complications and Litigation Associated With Injectable Facial Fillers: A Cross-Sectional Study. , 2021, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[6]  B. Chaput,et al.  Flap Venous Congestion and Salvage Techniques: A Systematic Literature Review , 2021, Plastic and reconstructive surgery. Global open.

[7]  M. Murad,et al.  A Systematic Review Supporting the American Society for Dermatologic Surgery Guidelines on the Prevention and Treatment of Adverse Events of Injectable Fillers. , 2020, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[8]  S. Hewitt,et al.  IGF-1 receptor signaling regulates type II pneumocyte senescence and resulting macrophage polarization in lung fibrosis. , 2020, International journal of radiation oncology, biology, physics.

[9]  J. Biernaskie,et al.  Single‐cell transcriptomic analysis of small and large wounds reveals the distinct spatial organization of regenerative fibroblasts , 2020, Experimental dermatology.

[10]  P. Janmey,et al.  Mechanical and Non‐Mechanical Functions of Filamentous and Non‐Filamentous Vimentin , 2020, BioEssays : news and reviews in molecular, cellular and developmental biology.

[11]  Wei-Qiang Tan,et al.  Current potential therapeutic strategies targeting the TGF-β/Smad signaling pathway to attenuate keloid and hypertrophic scar formation. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[12]  T. Alster,et al.  Dermatologic Laser Side Effects and Complications: Prevention and Management , 2020, American Journal of Clinical Dermatology.

[13]  D. Pieper,et al.  Evidence and Trends in Burn Wound Debridement: An Evidence Map , 2020, Plastic surgery.

[14]  H. Hoeksema,et al.  Eschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: European consensus guidelines update. , 2020, Burns : journal of the International Society for Burn Injuries.

[15]  K. Ramkumar,et al.  Macrophage mediation in normal and diabetic wound healing responses , 2020, Inflammation Research.

[16]  Jun Zhou,et al.  Adiponectin in renal fibrosis , 2020, Aging.

[17]  Xiufen Zheng,et al.  Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206+ M2-like macrophage polarization , 2020, Cell Death & Disease.

[18]  Won Lee,et al.  "Comparative Effectiveness of Different Interventions of Perivascular Hyaluronidase". , 2020, Plastic and reconstructive surgery.

[19]  E. Kalabusheva,et al.  Regeneration of Dermis: Scarring and Cells Involved , 2019, Cells.

[20]  Hsien-Da Huang,et al.  Mechanical stretch induces hair regeneration through the alternative activation of macrophages , 2019, Nature Communications.

[21]  C. Chuong,et al.  The tension biology of wound healing , 2019, Experimental dermatology.

[22]  A. S. Menko,et al.  In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype , 2018, Molecular biology of the cell.

[23]  Y. Jang,et al.  Recent Understandings of Biology, Prophylaxis and Treatment Strategies for Hypertrophic Scars and Keloids , 2018, International journal of molecular sciences.

[24]  A. Trentin,et al.  Skin wound healing in humans and mice: Challenges in translational research. , 2017, Journal of dermatological science.

[25]  H. Hoeksema,et al.  Eschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: An European consensus. , 2017, Burns : journal of the International Society for Burn Injuries.

[26]  T. Wynn,et al.  Type 2 immunity in tissue repair and fibrosis , 2017, Nature Reviews Immunology.

[27]  Lenie J. van den Broek,et al.  Burn Eschar Stimulates Fibroblast and Adipose Mesenchymal Stromal Cell Proliferation and Migration but Inhibits Endothelial Cell Sprouting , 2017, International journal of molecular sciences.

[28]  J. H. Lee,et al.  Scar Prevention and Enhanced Wound Healing Induced by Polydeoxyribonucleotide in a Rat Incisional Wound-Healing Model , 2017, International journal of molecular sciences.

[29]  R. Z. Murray,et al.  Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing , 2017, International journal of molecular sciences.

[30]  J. A. Farina,et al.  Revisiting Escharotomy in Patients With Burns in Extremities , 2017, Journal of burn care & research : official publication of the American Burn Association.

[31]  Hong Jiang,et al.  Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury. , 2017, Journal of the American Society of Nephrology : JASN.

[32]  Paul Martin,et al.  Inflammation and metabolism in tissue repair and regeneration , 2017, Science.

[33]  T. Wynn,et al.  Mechanisms of Organ Injury and Repair by Macrophages. , 2017, Annual review of physiology.

[34]  B. Hinz The role of myofibroblasts in wound healing. , 2016, Current research in translational medicine.

[35]  K. Harding,et al.  Wound bed preparation: TIME for an update , 2016, International wound journal.

[36]  T. Wynn,et al.  Macrophages in Tissue Repair, Regeneration, and Fibrosis. , 2016, Immunity.

[37]  G. Duckwiler,et al.  Rethinking the Role of Nitroglycerin Ointment in Ischemic Vascular Filler Complications: An Animal Model With ICG Imaging , 2016, Ophthalmic plastic and reconstructive surgery.

[38]  Tammara A. Wood,et al.  Myofibroblasts in Murine Cutaneous Fibrosis Originate From Adiponectin‐Positive Intradermal Progenitors , 2015, Arthritis & rheumatology.

[39]  P. Arasteh,et al.  Early Excision and Grafting versus Delayed Skin Grafting in Burns Covering Less than 15% of Total Body Surface Area; A Non- Randomized Clinical Trial. , 2014, Bulletin of emergency and trauma.

[40]  Saeid Amini-Nik,et al.  Animal models in burn research , 2014, Cellular and Molecular Life Sciences.

[41]  P. V. van Zuijlen,et al.  Objective Scar Assessment Tools: A Clinimetric Appraisal , 2011, Plastic and reconstructive surgery.

[42]  R. White,et al.  Management of minor acute cutaneous wounds: importance of wound healing in a moist environment , 2011, Journal of the European Academy of Dermatology and Venereology : JEADV.

[43]  Werner Müller,et al.  Differential Roles of Macrophages in Diverse Phases of Skin Repair , 2010, The Journal of Immunology.

[44]  N. Gibran,et al.  Surgical excision of the burn wound. , 2009, Clinics in plastic surgery.

[45]  Joel L Cohen Understanding, Avoiding, and Managing Dermal Filler Complications , 2008, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[46]  Herbert Tilg,et al.  Adipocytokines: mediators linking adipose tissue, inflammation and immunity , 2006, Nature Reviews Immunology.

[47]  D. Church,et al.  Burn Wound Infections , 2006, Clinical Microbiology Reviews.

[48]  Wei-qiang Tang,et al.  Evaluation of Intra-arterial Thrombolysis in Treatment of Cosmetic Facial Filler-related Ophthalmic Artery Occlusion. , 2019, Plastic and reconstructive surgery.