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Reprogramming Wound Healing: GAG-Based Bioactive Scaffold Drives Pro-Regenerative Cellular Cross-Talk
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DOI：10.1002/jbm.b.70062.png)
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Abstract
En 中文
Effective wound healing depends on coordinated fibroblast-macrophage cross-talk that governs the transition from inflammation to regeneration. Here, we evaluated whether a glycosaainoglycan (GAG)-based viscoelastic scaffold composed of chitosan, chondroitin sulfate, and hyaluronic acid (CH-(CS-HA)) can modulate this cross-talk and promote regenerative repair. In vitro coculture studies demonstrated excellent cytocompatibility and significant phenotypic modulation. In fibroblasts, alpha-SMA (acta2) expression increased similar to 4.4-fold, and fibronectin (fn1) was markedly upregulated at 96 h in the CH-(CS-HA) + conditioned media (CM) group. Importantly, the Col-I/Col-III (col1a1/col1a3) ratio decreased from similar to 2.1 to similar to 1.1 over time, while the TGF-beta 1/TGF-beta 3 (tgfb1/tgfb3) ratio shifted from similar to 2.0 to similar to 0.7, indicating antifibrotic ECM remodeling. In macrophages, CD86 (Cd86) expression decreased from similar to 2.8-fold to similar to 1.5-fold, whereas CD206 (Mrc1) increased from similar to 3.4-fold to similar to 6.7-fold between 48 and 96 h, confirming M2 polarization. The TGF-beta 1/TGF-beta 3 (tgfb1/tgfb3) ratio similarly declined from similar to 1.0 to similar to 0.3, reinforcing an anti-inflammatory phenotype. In a full-thickness rat wound model, CH-(CS-HA) treatment achieved similar to 91% wound closure by day 17 compared to similar to 63% in controls. Gene expression in healed tissue showed elevated tgfb3 (similar to 6.4-fold) relative to tgfb1 (similar to 4.3-fold), increased col1a1 (similar to 5.3-fold) with reduced col1a3 (similar to 2.7-fold), and enhanced acta2 and fn1 expression, consistent with organized matrix maturation. Histology confirmed complete re-epithelialization and early hair follicle regeneration. Collectively, these findings demonstrate that CH-(CS-HA) orchestrates immune-stromal cross-talk to promote inflammation resolution, balanced ECM remodeling, and functional tissue regeneration.
Keywords:
cell-grafting
chitosan
chondroitin sulfate
cross-talk
hyaluronic acid
tissue regeneration
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