Bacterial cellulose-silk sericin (BC-SS) biomaterials enhance the in vitro proliferation of skin cells, forecasting an ability to accelerate wound healing. In a previous study, fibroblasts aligned along the stripes of microstructured BC-SS (mBC-SS), whereas randomly distributed on smooth BC-SS (rBC-SS). Therefore, we hypothesized that in vivo, collagens produced by fibroblasts and pivotal for wound contraction could follow the alignment of these cells, which would prevent excessive fibrosis and scaring. The current work reports the in vivo evaluation of rBC-SS2 and mBC-SS2 in full-thickness wounds. Overall, improved healing rates were obtained with the composites than pure BC. Especially, mBC-SS2 induced complete wound closure with hair growth at day 14. Early infiltration of inflammatory cells, fibroblasts and keratinocytes with the composites led to faster re-epithelialization, vascularization, and wound contraction. Interestingly, mBC-SS2 prevented the excessive wound contraction responsible for hypertrophied neo-tissue formation upon application of rBC-SS2, enhancing healing while containing fibrosis and scar formation.