Role of Ultrathin Skin Graft in Early Healing of Diabetic Foot Ulcers

A Randomized Controlled Trial in Comparison With Conventional Methods

Rahul Shetty, MBBS, MS, MCh, DNB; BS Giridhar, MBBS, MS; Ankush Potphode, MBBS, DNB


Wounds. 2022;34(2):57-67. 

In This Article

Abstract and Introduction


Introduction: Diabetic foot ulcers (DFUs) are a global burden on health care systems. Despite the availability of various treatment modalities, many DFUs do not heal. Nonhealing wounds can lead to various complications, which add to significant morbidity in terms of the degree of moisture retained in the dressing, pain, foul order, and restriction of daily activities. A different treatment modality that can promote the wound healing process earlier (and is cost-effective, easy to use, and readily available) may be necessary to consider.

Objective: The purpose of the current study was to demonstrate the efficacy of ultrathin skin grafting (UTSG) in the early healing of DFUs in terms of cost-effectiveness, reduced total number of hospital visits, and final wound outcome (ie, limb salvage rate).

Materials and Methods: A randomized controlled trial was conducted in which 52 patients were treated with either UTSG (test group) or conventional dressing (control group). Both groups were compared by time to healing, number of hospital visits, cost, and final outcome of the wound.

Results: By the end of the 12-week study period, 84.61% of wounds managed with UTSG healed completely, whereas only 53.84% of wounds managed with conventional methods achieved complete healing. The test group achieved a more than 50% wound size reduction within 6 weeks after grafting. There were fewer hospital visits for the test group, indicating this grafting technique was more cost-effective than the control group.

Conclusions: As demonstrated in this study, UTSG appears to be beneficial in achieving faster healing of DFUs and improving the final outcome of the wound.


With a rising prevalence worldwide, diabetes mellitus (DM) is a burden on the health care systems.[1] Diabetes mellitus is becoming more common; the number of people living with DM increased 1.5 fold from 463 million, and the prevelance is expected to reach 700 million in 2045.[2] After China, India has the second-highest population of individuals with diabetes.[3] Diabetes is associated with multiple complications, including diabetic foot ulcers (DFUs).

According to the International Working Group on the Diabetic Foot (IWGDF), a DFU is a full-thickness wound passing through the dermis and located below the ankle in a patient with diabetes.[4] It is estimated that 15% of patients with DM will experience a DFU in their lifetime;[5] if these patients are not treated in a timely manner, a DFU can progress to infection, osteomyelitis, or gangrene, which can lead to amputation. As many as 8 in 10 nontraumatic amputations can be attributed to DM, and 85% of such amputations result from DFUs.[5] Mortality after unilateral limb amputation varies, with the risk between 13% and 40% at 1 year, between 35% and 65% at 3 years, and between 39% and 80% at 5 years.[5] However, it has been estimated that the majority of these amputations can likely be prevented.[6]

Microangiopathy is one of the main pathologic conditions underlying the slow, insufficient, or nonhealing nature of a DFU.[7] Other pathologic conditions include decreased or impaired growth factor production, collagen accumulation, and quantity of granulation tissue.[8] Conventional treatment methods involve initial debridement and multiple dressings. Treatment could include repeat debridements and a long follow-up period until complete wound is achieved; long follow-up period is considered to exceed 3 months in this study. Many wounds take longer than expected to heal, resulting in an increased morbidity rate and health care costs. The estimated 5-year mortality is up to 30.65%, and the cost burden is equivalent to that of cancer.[9]

Standard therapy for managing DFUs involves glycemic control, antibiotic coverage, debridement of necrotic tissue, regular dressing changes, and offloading footwear. Several recent modalities have been introduced, such as various types of dressing, including negative pressure wound therapy (NPWT), offloading, growth factor application, and bioengineered skin constructs.[10]

Although NPWT shows promising results, it has disadvantages such as the need for multiple sittings, foam dressing fragmentation and retention, and difficulty maintaining effective suction. There may be a requirement for a definitive skin grafting procedure for coverage to encourage complete healing.[11,12] Hyperbaric oxygen therapy can enhance wound healing; however, it is not always readily available and may not be adequate for use in patients with large wound sizes involving more than 70% area of the foot, surrounding edema, and loss of tissue for local coverage.[13] In addition, many complications have been associated with hyperbaric oxygen treatment. Topical growth factors can promote wound healing; however, it is costly and not readily available, and more conclusive studies are necessary to support the efficacy of such treatment.[14] Split-thickness skin grafting (STSG) can be used to manage and close DFUs. Still, it can be used only when the wound bed is healthy, with sufficient granulation tissue, which in turn could demand multiple, regular saline-gauze dressings or NPWT applications.[15] Often, even STSG may not be sufficient.

Conventional treatments for DFUs could be associated with more hospital visits and a longer healing time, which would add to the patient's health care cost and potentially affect their overall quality of life. The cost involved, availability of the treatment, and frustration with the lack of healing can significantly affect patient adherence.[16] Considering the socioeconomic circumstances of the population in India in particular, these factors may contribute to poor patient adherence to the treatment protocol, leading to further complications associated with DFUs.[17]

Galiano et al[18] demonstrated the efficacy of topical vascular endothelial growth factor (VEGF) application on DFUs and observed accelerated wound healing through increased angiogenesis. Osborne et al[19] demonstrated growth factor secretion ability in cell cultures of epidermal micrografts. They identified the presence of various growth factors such as VEGF and endothelial growth factor using immunohistochemistry. Based on these studies,[18,19] the authors of the current study proposed that epidermal micrografts might be used on DFUs, which could improve healing by initiating growth factor secretion at the wound bed. Such grafts might also act as a primary cover for wound closure.

In a prospective study, Hachach- Harametal[20] proposed a method of epidermal grafting using an automated tool (epidermal graft harvesting device; CELLUTOME Epidermal Harvesting System; 3M) in an outpatient setting, resulting in minimal or no pain and a scar-free donor site. A case series based in India demonstrated promising results of epidermal grafting as a potentially suitable option for managing chronic, complex wounds when only the epidermal layer is required.[21] The epidermal skin graft has only been previously used on a wound in which the wound bed had sufficient granulation tissue formation (before multiple dressings or NPWT applications were used for wound bed preparation). To the authors' knowledge, epidermal skin grafts have not demonstrated the ability to secrete growth factors, which may result in better healing outcomes. With considering the above, the current authors explored using epidermal skin grafting (ultrathin skin grafting; UTSG) in the management of DFUs.

A newer treatment modality is needed for managing DFUs that addresses the problem of delayed healing by reducing follow-up time and treatment cost as well as being readily available. The purpose of the current study was to demonstrate the efficacy of UTSG in the early healing of DFUs in terms of cost-effectiveness, reduced total number of hospital visits, and a better final outcome of the wound (ie, limb salvage rate).