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Background: Avascular wounds represent a significant challenge in medical care due to impaired blood flow. Synthetic matrices, such as poly-lactic acid (PLA), have demonstrated promising results in promoting wound healing in complex wounds, including those with restricted blood supply, such as diabetic foot and venous leg ulcers. Objective: This case series presents the outcomes of five patients with avascular wounds of various etiologies successfully treated with PLA matrices. Case description: Five patients presented complex wounds involving exposure of bone, tendon, fascia, or osteosynthetic material. Wound bed preparation included debridement followed by PLA application covered with additional layers (non-adherent dressing, absorbent dressing, and compression bandage) as needed. Weekly assessments were conducted until full wound closure was achieved. Results: All cases showed successful outcomes, with PLA promoting granulation tissue formation and re-epithelialization, contributing to wound closure. One patient required skin grafts for complete healing. No local infections were reported before or after PLA application. Conclusion: PLA matrices are a practical and effective option for managing complex avascular wounds, promoting tissue regeneration and optimizing wound bed quality for skin grafts or flaps. While these findings are promising, further studies are needed to confirm the broader applicability and efficacy of PLA in avascular wound management.