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• Rooibos extract loaded hydrogels (RH) displayed therapeutic properties in vivo. • RH dressing accelerated healing of uncomplicated acute surgical wounds. • Fermented rooibos extract was more effective than green rooibos extract. • Rooibos extracts reduced infiltration of inflammatory cells in granulation tissues. Aspalathus linearis (rooibos) has been reported to have a high content of phenolic compounds which elicit antioxidant and anti-inflammatory activity in biological systems. In the present study, we evaluated the effects of "fermented" (oxidised) and green rooibos extracts embedded in gentamicin loaded acrylate copolymer based hydrogels on inflammatory response in surgical wounds in vivo. The major phenolic compounds and a phenolic precursor present in the rooibos extracts were quantified by HPLC. Acute toxicity of the extracts in Swiss albino mice was evaluated up to 1 g/kg body weight. A modification of free radical initial polymerisation of the alkyl acrylate polymer was utilised to formulate hydrogels loaded with different concentrations of the extracts. The hydrogels were evaluated for swelling, skin irritancy, gel index and pH. Surgical wounds were inflicted on 40 healthy male Sprague Dawley rats, randomly designated to groups treated with the extract loaded hydrogels, hydrogel (without extract; control) and 1% framycetin sulphate containing gauze (positive control). In vivo wound healing test post-surgical intervention was carried out following histomorphometric studies. All extract loaded hydrogels shortened the time taken for complete wound closure compared to the control. Hydrogels loaded with fermented rooibos extract performed better than those loaded with green rooibos extract or the positive control by significantly (p < 0.05) shortening the time to complete wound closure from 14 to 10 days. The histologic section of skin showed the absence of inflammatory cell infiltrates within the underlying dermis and subcutaneous fat for all extract loaded hydrogels and no increased dermal stromal fibrosis or other abnormalities in three of the fermented rooibos extract and two unfermented rooibos extract hydrogel formulations compared to the control (p < 0.05). Therapeutic properties of green and fermented rooibos extract loaded hydrogels have been established in vivo , with the best wound healing indices shown by the hydrogels containing fermented rooibos extract. This is possibly a result of a shorter inflammatory phase resulting in quicker wound closure and reduced fibrosis. [ABSTRACT FROM AUTHOR]