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Objective: Peripheral arterial disease results from obstructed blood flow in arteries and increases the risk of amputation in acute cases. Therapeutic angiogenesis using bioengineered tissues composed of a chitosan scaffold that was enriched with mast cells (MCs) and/or platelet-rich plasma (PRP) was used to assess the formation of vascular networks and subsequently improved the functional recovery following hindlimb ischemia. This study aimed to find an optimal approach for restoring local vascularization. Materials and Methods: In this experimental study, thirty rats were randomly divided into six experimental groups: a. Ischemic control group with right femoral artery transection, b. Ischemia with phosphate-buffered saline (PBS) control group, c. Ischemia with chitosan scaffold, d. Ischemia with chitosan and MCs, e. Ischemia with chitosan and PRP, and f. Ischemia with chitosan, PRP, and MCs. The left hind limbs served as non-ischemic controls. The analysis of capillary density, arterial diameter, histomorphometric analysis and immunohistochemistry at the transected locations and in gastrocnemius muscles was performed. Results: The group treated with chitosan/MC significantly increased capillary density and the mean number of large blood vessels at the site of femoral artery transection compared with other experimental groups (P<0.05). The treatment with chitosan/MC also significantly increased the muscle fiber diameter and the capillary-to-muscle fiber ratio in gastrocnemius muscles compared with all other ischemic groups (P<0.05). Conclusion: These findings suggested that chitosan and MCs together could offer a new approach for the therapeutic induction of angiogenesis in cases of peripheral arterial diseases. [ABSTRACT FROM AUTHOR]