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Abstract: Many patients are affected by HIV/AIDS, and these conditions are highly prevalent worldwide. Patients with HIV/AIDS can experience debilitating wound infections that often require flap reconstruction and become challenging for surgeons to treat. In the past 5 years, mesenchymal stem cells have been tested and used as regenerative therapy to promote the growth of tissues throughout the body because of their ability to successfully promote cellular mitogenesis. To the authors' knowledge, the use of mesenchymal stem cell grafting following necrosis of a myocutaneous gracilis flap (as part of perineal wound reconstruction) has never been reported in the literature.In addition, the use of mesenchymal stem cells and regenerative medicine combined in the setting of squamous cell carcinoma of the anus with prior radiation (along with comorbid AIDS) has not been previously documented.In this report, the authors outline the case of a 60-year-old patient who had a recipient bed (perineum) complication from prior radiation therapy. Complicating the clinical picture, the patient also developed a Pseudomonal organ space infection of the pelvis leading to the failure of a vertical rectus abdominis myocutaneous flap and myocutaneous gracilis flaps. As a result, the patient underwent serial operative debridements for source control, with the application of mesenchymal stem cells, fetal bovine dermis, porcine urinary bladder xenograft, and other regenerative medicine products, achieving a highly successful clinical outcome. A procedural description for future use and replication of this method is provided., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)