Management and treatment of acute severe diabetic foot disease in patients with suboptimal glycaemic control is a critical issue in wound repair. This paper discusses the clinical efficacy of an aggressive surgical intervention combined with targeted use of regenerative medical therapies in limb preservation. Negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), bilayered acellular matrix grafting and split-thickness skin grafting were combined to treat a patient with diabetes, foot necrotising fasciitis and gaseous gangrene. The wound was completely healed. The clinical outcome revealed that a multi-intervention strategy could be effective for large necrotising fasciitis wounds. Early clinical observation, suggests aggresive surgical intervention preserving intact tissue and targeted use of new regenerative technologies can lead to preservation of a limb.