Accelerating Diabetic Wound Healing by Modulating the Inflammatory Environment Using Quercetin–Rosemary Oil Lipid Nanoemulsions with Artificial Intelligence‐Based Wound Closure Analysis

Abstract

Diabetic wounds are a significant complication of diabetes that is characterized by delayed wound healing and a high risk of amputation. Pro‐inflammatory macrophages (M1) and Matrix Metallo protease‐9 (MMP‐9) overexpression play pivotal roles in the extended inflammatory phase observed in diabetic wounds. This study developed a multifunctional lipid nanoemulsion containing quercetin and rosemary oil (Q‐RLNE) that can efficiently convert M1 macrophages to M2, inhibit MMP‐9, and prevent microbial infection, accelerating diabetic wound healing. In‐vitro studies demonstrated that Q‐RLNEs showed excellent biocompatibility and cellular uptake. Additionally, Q‐RLNEs demonstrated effective ROS scavenging, macrophage polarization, MMP‐9 inhibition, and excellent anti‐microbial properties against Staphylococcus aureus (S. aureus). In‐vivo results demonstrated that Q‐RLNE can accelerate and achieve complete wound healing in diabetic‐induced rats by reducing inflammation and promoting angiogenesis with proper collagen deposition and dermal projection regeneration. This study also highlighted the application of the Segment Anything Model (SAM) for precise wound region segmentation. SAM combines attention‐fusion and hybrid fusion strategies for accurate segmentation, enabling comprehensive analysis of wound attributes over time and guiding treatment decisions. The SAM analysis results also align with Q‐RLNE in‐vitro and in‐vivo. The findings of this study suggest that Q‐RLNE is a promising new therapeutic agent for accelerating diabetic wound healing.This article is protected by copyright. All rights reserved

Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds

“…Without laser irradiation, the QRLNE and QCRLNE-treated groups have shown maximum migration of 98.88% ± 0.3% and 99.01% ± 0.18%, respectively (as quantified in Figure b), was seen when compared to the RLNE-treated group with 67.3% ± 9.05% (Figure S4b,d), the CRLNE-treated group with 79.64% ± 9.32%, and the control with 79.69% ± 7.34% (Figure a,b). The maximum migration of QRLNE and QCRLNE can be attributed to quercetin’s antioxidant and anti-inflammatory properties and rosemary oil. ,,, After irradiation with a 690 nm laser for 5 min, the QRLNE and QCRLNE-treated groups showed similar migration to the nonirradiated groups (Figure a,b). In the control + NIR-treated group, the migration was less, which can be attributed to the continuous thermal effect of the NIR laser, which might retard the migration of the cells.…”

“…As shown in Figure b, tail transection significantly increased neutrophil recruitment at the injury site, indicating inflammation in the untreated group. In contrast, the tail-transected zebrafish treated with QRLNE and QCRLNEs showed a significant decrease in neutrophil recruitment and tail regeneration (Figure c), suggesting potential anti-inflammatory activity and accelerated wound healing properties of QRLNE and QCRLNEs due to the presence of quercetin and rosemary oil. ,, However, CRLNE showed no significant decrease in neutrophil recruitment (Figure b,c). Thus, QRLNE and QCRLNEs appear to have more pronounced anti-inflammatory and wound healing effects than CRLNEs.…”

“…QCRLNEs were prepared using a previously described method . Briefly, the oil phase consisted of rosemary oil (5 mg), chlorin e6 (1 mg) dissolved in 1 mL of chloroform, quercetin (5 mg) dissolved in ethanol, and egg lecithin (50 mg) dissolved in 1 mL of chloroform.…”

“…These fluorescent images were captured using a fluorescence microscope. The percentage of wound closure was calculated using the following formula: , % wound 0.25em closure = Initial 0.25em scratch 0.25em width − Final 0.25em Scratch 0.25em width Initial 0.25em Scratch 0.25em width × 100 …”