Inadequate vasculature poses a significant challenge in the clinical translation of tissue engineering constructs. Current strategies for vascularization typically recruit short-lived endothelial cells or induce mesenchymal stem cells (MSC) to differentiate into the endothelial lineage, often in combination with supporting pericytes or fibroblasts. However, endothelial-associated cocultures lack adaptive ability and form limited vasculature. In this study, we investigated the endothelial transdifferentiation of an MSC-fibroblast coculture loaded on a bioengineered graft and utilized the exosomes released by the coculture model as a biomarker to monitor the progress of vascularization inside the graft. To develop the pre-vascularized skin graft, dermal fibroblasts and MSC were seeded on a biocomposite chitosan/collagen/fibrinogen/D3 (CCF-D3) scaffold. The cocultured graft facilitated the differentiation of MSC to endothelial cells (MEnDoT). Additionally, it promoted vasculogenic sprouting through the VEGF-eNOS pathways, as evidenced by the expression of F-actin, VEGF-A, and downstream transcriptomic markers (CD31, CD34, eNOS, VEGF-A, VEGF-R2, PI3 K, and PLC-γ). Exosomes (∼130 nm diameter) were isolated from the coculture, and their spectral analysis revealed significant differences (