Diabetic foot ulcer (DFU) is one of the most challenging complications in patients with diabetes and it has a lifetime incidence of 15–25%.1 Impaired diabetic wound healing has become an important cause of non-traumatic lower-limb amputation worldwide, and it progresses to major amputation in 14–24% of patients.2 These intractable and refractory wounds pose a challenge in plastic surgery. The main goal of the specialist is to accelerate wound closure and lower the amputation rate to improve patients’ outcomes. The purpose of this article is to describe a new clinical practice in a patient with a severe DFU classified as grade IIID (in accordance with the University of Texas Diabetic Wound Classification)3 by applying autologous fat grafting (AFG) and negative pressure wound therapy (NPWT).
Case presentation
A 65-year-old female patient, with a history of diabetes and renal failure, was admitted to our department with a right DFU and fever. Several months previously, the treatment she received in the local hospital had involved washing, dressing changes and antibiotic treatment to prevent the wound from progressing. The treatment was unsuccessful and her second toe was removed. Amputation of the foot had been suggested, but the patient always refused it.
Physical examination showed that, on the sole of the right foot, there was a 10cm-long full-thickness skin defect, which had invaded the deep fascia and muscle. A fistula had formed between the second metatarsophalangeal joint and pelma, with purulent discharge which gave a fetid odour (Fig 1a). The dorsalis pedis pulse diminished along with foot sensory disturbances. Ultrasound of the lower limb vascular tree was carried out and imaging showed arteriosclerosis. Plain radiography of the right foot demonstrated that the distal and proximal part of the third metatarsal bone was damaged and the base proximal segment of the fourth metatarsal bone was fractured (Fig 1b). The laboratory findings are shown in Table 1.
Table 1. Laboratory examinations at hospital admission
| Test | Result |
|---|---|
| C-reactive protein (mg/l) | 170.83* |
| Haemoglobin (g/l) | 66† |
| Total protein/albumin (g/l) | 58.3b/26.6† |
| Blood urea nitrogen (mmol/l) | 12.09* |
| Creatinine (μmol/l) | 419.58* |
below normal range
Medical treatment upon hospital admission included: antibiotics and supportive therapy to control infection, insulin injection to control blood glucose, haemodialysis to treat renal failure, and blood products transfusion to relieve anaemia and hypoproteinaemia. When there were no surgical contraindications, we performed the first surgery. After debridement of the ulcer, we harvested adipose tissue from the patient's abdomen (method of Coleman4) and injected purified fat tissue into the wound bed and subcutaneous tissue surrounding the ulcer, and treated the wound with NPWT. After 14 days, we removed the NPWT device: new granulation tissue had covered all of the wound surface (Fig 2a). The second surgery was performed to close the wound by split thickness skin grafting; sutures were employed and the NPWT remained with the aim of promoting skin graft survival. Some 10 days later, we removed the NPWT device and observed that most of the graft had survived. Regular dressing changes were carried out on alternate days. The patient was discharged after a total of 49 days in hospital, by which time most of the wound was re-epithelialised (Fig 2b).
Ethics
This research was approved by our hospital's ethics committee (reference: GRYY-LL-KJ2021-K8). Informed consent was obtained from the patient to participate in the study and for the findings to be published, including the photographs.
Discussion
DFUs, which have high prevalence, slow wound healing, many complications and a high incidence of amputation, have a serious impact on the quality of life of patients with diabetes. NPWT is a well-characterised method of therapy for DFUs.5 Previous studies have proved that NPWT is able to promote the formation of granulation tissue6 and increase the level of angiogenesis, accelerate revascularisation,7 increase the local blood perfusion8 and thus stimulate extracellular matrix remodelling.9 However, according to our previous clinical observations,10 when using NPWT alone, the DFUs associated with neuropathy, peripheral vascular disease with ischaemia, coupled with hyperglycaemia and infection, have poor treatment results. A possible reason might be the vacuum environment created by NPWT which causes local hypoxia, aggravating the ischaemia.11
AFG is an emerging therapy for complicated wounds. Animal and clinical experimental studies have demonstrated that grafting fat tissue in hard-to-heal wounds promotes tissue repair. Preclinical evidence demonstrates that numerous cells in adipose tissue, such as adipocytes, preadipocytes, adipose-derived stem cells (ASCs) and macrophages12 also play a vital role in the formation of granulation tissue, promoting wound healing and regeneration,13 differentiating into cutaneous appendages,14 and secreting a variety of cytokines and growth factors.15 The main cytokines and growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-β), insulin-like growth factor-1 IGF-1 and angiopoietin (ANGPT), which could support soft tissue regeneration and remodelling.16 This type of function could be enhanced in hypoxic environments.12 These features seem to help the wound healing progress and the outcome detailed in our case report seems to demonstrate this.
These clinical effects might explain how previous studies have shown that AFG has a therapeutic effect on refractory wounds such as post-radiation dermatitis ulcers and venous ulcers. In addition, AFG may halt progression of existing wounds: Mohan and Singh17 cured a post-radiation dermatitis ulcer with AFG instead of complex surgical procedures; and Williams and Thaller18 have shown that, for the patient with a hard-to-heal ulcer, AFG may produce a better outcome for skin graft and prevent further wound breakdown.
Conclusion
According to current molecular research and clinical practice, fat transplantation is effective in promoting wound healing. In conclusion, fat transplantation is a promising development as a method in the field of tissue reconstruction and will be a new topic in the field of plastic surgery.
Reflective questions
- How can autologous fat tissue help wound healing?
- How do negative pressure wound therapy (NPWT) and autologous fat grafting (AFG) interact and promote each other during the healing process?