An extracellular matrix (ECM) mimicking architecture was introduced with gelatin glycosaminoglycans like hyaluronic acid and chondroitin sulfate and a triterpenoid using asiatic acid, possessing biodegradable and biocompatible properties that mark the functionality for the treatment of second-degree burn wounds. In the present work, a foam-based scaffold was fabricated and sterilized with gamma radiation at a 2.5 Mrad dose. The scaffolds were further characterized for morphology, swelling, degradation behaviour, release of bioactive components, ATR-FTIR, mechanical, thermal properties and compared with control. In vitro cytocompatibility of the developed scaffold was studied with L929 mouse fibroblast cells and human mesenchymal stem cells based on deoxyribonucleic acid and lactate dehydrogenase assay. Additionally, the developed scaffold was evaluated for its biocompatibility on the Wistar rat to assess any toxicity induced to the animal based on blood biochemistry and histopathology analysis. Finally, we assessed the efficacy of developed foam scaffolds on the second-degree burn wound-induced Wistar rat with a scaffold alone and a scaffold seeded with human bone-marrow-derived mesenchymal stem cells in a wound healing study for 28 d. The wound contraction assay, histopathology, immunohistochemistry analysis and pro-healing marker quantification using hexosamine, hydroxyproline, and pro-inflammatory markers like TNF-α and MMP-2 were carried out and compared with the commercially available wound dressing. The results revealed that foam-based ECM mimic was cytocompatible, biocompatible and biodegradable in 18 ± 3 d in in vivo conditions and the scaffold fostered the process of healing of second-degree burns within 28 d of treatment. The obtained result proved that the scaffold has a potential for clinical settings in second-degree burn wound treatment.