Stabilized Collagen Matrix Dressing Improves Wound Macrophage Function And Epithelialization
Mohamed S. El Masry1, AMITAVA DAS1, Scott Chaffee1, Piya Das Ghatak1, Shomita Mathew-Steiner1, Natalia Higuita-Castro1, Raafat A. Anani2, Sashwati Roy1, Chandan K. Sen1.
1Department of Surgery, Center for Regenerative Medicine and Cell Based Therapies and Comprehensive Wound Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA, 2Department of General Surgery,Zagazig University, Zagazig, Egypt.
Background: Naturally derived biomaterials such as decellularized matrix of biological tissue have performed very well as wound care dressings. Such dressings present the advantage of native extracellular matrix. However, the challenge faced by any ECM-based wound care dressing product is their rapid degradation by the excessive MMPs and other proteases present in the wound environment. Stabilized, acellular, equine pericardial collagen matrix (sPCM) wound care dressing is prepared by decellularization, stabilization and sterilization of equine pericardium. However, the mechanism of action remains unclear. Methods: A murine excisional wound model was employed to study wound healing. Wound macrophages harvested from PVA sponges were used for the study. Results: The dressing was structurally characterized utilizing scanning electron and atomic force microscopy. Based on macrophage count by flow cytometric analysis and cytokine response, post-wound inflammation resolved rapidly as indicated by elevated levels of pro-resolution genes such as IL-10, Arginase-1 and VEGF and lowering of pro-inflammatory cytokines IL-1β and TNFα. sPCM induced antimicrobial proteins S100A9 and β-defensin-1 in keratinocytes (n=5,*p≤ 0.05). Inhibition of biofilm formation was evident by IVIS imaging using a bioluminescent strain of P.aeruginosa (Xen41). Excisional wounds of C57bl/6 mice dressed with sPCM showed complete closure at day 14 while control wounds remained open (n=10,*p≤ 0.001). sPCM accelerated wound re-epithelialization. sPCM not only expedited wound closure but improved the quality of healing by increased collagen deposition and maturation. Conclusion: The naturally derived biomaterial sPCM is a single-application collagen-based wound dressing capable of presenting scaffold functionality during the course of wound healing. In addition to inducing endogenous antimicrobial defense systems, it mounts robust inflammation, that rapidly resolves making way for wound healing to advance. Randomized clinical trial testing of this promising dressing material in a clinical setting is warranted.
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