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Background: Wound healing is a complex biological process. Some injuries lead to chronic nonhealing ulcers, and healing process is a challenge to both the patient and the medical team. We still look forward an appropriate wound dressing. Materials and Methods: In this study, starch-based nanocomposite hydrogel scaffolds reinforced by zeolite nanoparticles (nZ) were prepared for wound dressing. In addition, a herbal drug (chamomile extract) was added into the matrix to accelerate healing process. To estimate the cytocompatibility of hydrogel dressings, fibroblast mouse cells (L929) were cultured on scaffolds. Then, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide assay test and interaction of cells and scaffolds were evaluated. For evaluating healing process, 48 male rats were randomly divided into four groups of four animals each (16 rats at each step). The ulcers of the first group were treated with the same size of pure hydrogels. The second group received a bandage with the same size of hydrogel/extract/4 wt% nZ (hydrogel NZE). The third group was treated with chamomile extract, and the fourth group was considered as control without taking any medicament. Finally, the dressings were applied on the chronic refractory ulcers of five patients. Results: After successful surface morphology and cytocompatibility tests, the animal study was carried out. There was a significant difference between starch/extract/4 wt% nZ and other groups on wound size decrement after day 7 (P < 0.05). At the clinical pilot study step, the refractory ulcers of all five patients were healed without any hypersensitivity reaction. Conclusion: Starch-based hydrogel/zeolite dressings may be safe and effective for chronic refractory ulcers. [ABSTRACT FROM AUTHOR]