INTRODUCTIONDiabetes causes complications like delayed wound healing for a long time. Fibroin, aloe vera, and ginger extracts along with their combinations are used for diabetic wound healing.METHODSAfter induction of diabetes, The wound healing effects of fibroin (50 mg/ml), aloe vera gel (50 mg/ml), and ginger extract (30 mg/ml), individually and in combination, were assessed. The pro-inflammatory cytokines including tumor narcosis factor-α (TNF-α) interleukin (IL-6, IL-8, IL-1β), matrix metalloproteinases (MMP 2, MMP7, MMP 9), vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs) levels were analyzed in the serum.RESULTSA combination of fibroin + aloe vera gel + ginger extract (Fi + Al + Gi) healed the wounds in 11 days via wound contraction of 98.5 ± 0.9 % as compared to diabetic control (58.2 ± 0.7 %) and positive control (73.3 ± 0.6 %) groups. However, the wounds of the Polyfax and the diabetic control groups were healed in 17 and 19 days, corresponding to a contraction of: 96.7 ± 1.4 % and 96.3 ± 1.1 %. The histological assay showed that the Fi + Al + Gi group indicated an increased growth of collagen fibers, fibroblasts, keratinocytes and blood vessels with lessened inflammation. The Fi + Al + Gi group alleviated the serum level of TNF-α (12.7 ± 0.9 pg/ml), IL-6 (9.6 ± 0.9 pg/ml), IL-8 (19.6 ± 1.0 pg/ml), MMP2 (217.0 ± 9.2 pg/ml), MMP7 (279.0 ± 9.8 pg/ml), and MMP9 (156.0 ± 11.6 pg/ml) significantly as compared to the diabetic control (P ≤ 0.05). TIMP serum level (202.0 ± 6.9 pg/ml) was significantly elevated as compared to the diabetes control group.CONCLUSIONThe present study concludes that the biomaterials in their combinations possess high regenerative and healing abilities.