Wound healing action of nitric oxide‐releasing self‐expandable collagen sponge

Abstract

Mounting evidence showing that local nitric oxide (NO) delivery may significantly improve the wound healing process has stimulated the development of wound dressings capable of releasing NO topically. Herein, we describe the preparation of a selfexpandable NO-releasing hydrolyzed collagen sponge (CS), charged with the endogenously found NO donor, S-nitrosoglutathione (GSNO). We show that cold pressed and GSNO-charged CS (CS/GSNO) undergo self-expansion to its original 3D shape upon water absorption to a swelling degree of 2,300 wt%, triggering the release of free NO. Topical application of compressed CS/GSNO on wounds in an animal model showed that exudate absorption by CS/GSNO leads to the release of higher NO doses during the inflammatory phase and progressively lower NO doses at later stages of the healing process. Moreover, treated animals showed significant increase in the mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1), murine macrophage marker (F4/80), transforming growth factor beta (TGF-β), stromal cell-derived factor 1 (SDF-1), insulin-like growth factor-1 (IGF-1), nitric oxide synthase(iNOS), and matrix metalloproteinase(MMP-9). Cluster differentiation 31 (CD31), vascular endothelial growth factor (VEGF), and F4/80 were measured on Days 7 and 12 by immunohistochemistry in the cicatricial tissue. These results indicate that the topical delivery of NO enhances the migration and infiltration of leucocytes, macrophages, and keratinocytes to the wounded tissue, as well as the neovascularization and collagen deposition, which are correlated with an accelerated wound closure. Thus, self-expandable CS/GSNO may represent a novel biocompatible and active wound dress for the topical delivery of NO on wounds. K E Y W O R D S hydrolyzed collagen sponge, nitric oxide, S-nitrosoglutathione, topical application, wound healing Valéria C. O. Póvoa and Giovanna J. V. P. dos Santos contributed equally to this work.

Reduction in Foreign Body Response and Improved Antimicrobial Efficacy via Silicone-Oil-Infused Nitric-Oxide-Releasing Medical-Grade Cannulas

“…13,14,18,19 NO-releasing materials have shown significant progress in reducing foreign body response, 8,23 minimizing bacterial colonization, 11,24 improving hemocompatibility, 13,25,26 and accelerating wound healing. 27,28 However, the long-term efficacy of these surfaces is directly dependent on the material's ability to provide a stable, sustained NO release. In this study, the long-term NO release from SNAP-loaded cannulas (SR-SNAP-Si and SR-SNAP) was characterized in real time under moist conditions in vitro via chemiluminescence using NO analyzers with a response time of <1 s (Figure 1B).…”

Synthetic, Natural, and Semisynthetic Polymer Carriers for Controlled Nitric Oxide Release in Dermal Applications: A Review

“…Five years later, in 2020, three more platforms were published with a natural-based wound healing hydrogel as a carrier, namely by Nie et al [91], Póvoa et al [95], and Huang et al [94]. The first system was designed to treat diabetic wounds based on a cellulose gel containing nitric oxide and asiaticoside, an anti-inflammatory plant extract.…”

“…The second matrix was a "self-expandable" sponge produced by lyophilization of collagen with GSNO. They reported accelerated healing by an effectively bioabsorbable platform [95].…”

The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis

“…During wound healing processes of the respiratory mucosa, the deposition of fibrin matrix is replaced by collagen produced by fibroblasts. The biological actions of NO have been demonstrated to be crucial in the wound healing process and tissue regeneration [ 119 , 120 ]. Several lines of evidence indicate that NO induces the expression of collagen in human fibroblasts, and NO-releasing materials are currently being used in a scaffold in wound-repairing beds [ 121 , 122 ].…”