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A Modified Collagen Dressing Induces Transition Of Inflammatory To Reparative Phenotype Of Wound Macrophages
Amitava Das, Nirupam Biswas, Pradipta Banerjee, Nandini Ghosh, Savita Khanna, Chandan K. Sen and Sashwati Roy
Department of Surgery, IU Health Comprehensive Wound Center, Indiana Center for Regenerative Medicin
2019-02-15
Presenter: Amitava Das
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal.
Director Name: Chandan K. Sen
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Collagen based dressings are widely used in wound care. However understanding of their mechanism of action is scanty. Previous studies using a modified collagen gel (MCG) dressing demonstrated robust vascularization of ischemic wounds and improved healing outcomes. Wound macrophages are pivotal in enabling wound angiogenesis and timely healing. In this work, we sought to investigate the direct action of MCG dressing on wound macrophage phenotype and function using a established murine PVA sponge model. MCG increased macrophage recruitment to the wound site and attenuated pro-inflammatory (mϕinf) macrophage polarization (p˂0.05; n=3). Decreased mϕinf polarization was associated with increased production of anti-inflammatory cytokine IL-10 and proangiogenic VEGF (p˂0.05; n=6) indicative of a direct action of MCG in resolving wound inflammation and improving angiogenesis. Impaired clearance of apoptotic cell bioburden at wound-site enables chronic inflammation. Engulfment of apoptotic cells by macrophages (efferocytosis) drives polarization of macrophages to reparative phenotype via a miR-21-PDCD4-IL-10 pathway. Elevated efferocytosis index (p˂0.05; n=4) was noted in macrophages from MCG treated wounds. Such favorable outcome resulted in a significant induction (p˂0.05; n=4) of miR-21 expression. Interestingly, MCG-mediated induction of IL-10 was blunted under conditions of miR-21 knockdown (p˂0.05; n=4) by miR-21-zip pointing towards miR-21 as a causative factor. Pharmacological inhibition of JNK resulted in attenuated IL-10 (p˂0.05; n=4) production by MCG, implicating miR-21-JNK pathway in MCG-mediated IL-10 release by wound macrophages. This work presents direct evidence demonstrating that a collagen based wound care dressing may influence wound macrophage function and therefore modify wound inflammation outcomes.
