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

Disclosures

Wounds. 2022;34(2):57-67. 

In This Article

Results

A total of 56 patients were enrolled in the study. Of these, 3 were lost to follow-up before 12 weeks, and 1 patient received collagen dressing at the local clinic. Thus, 4 patients (2 from each group) were ineligible for inclusion. Data from 52 patients (26 in each group) were analyzed. Age distribution among both groups was statistically matched with the mean age in the test groups (56.92 and 57.79 years; P =.44, Student t test) (Table).

Sex distribution was matched, with 11 males and 15 females in the test group and 14 males and 12 females in the study group (P =.405 [moderately significant] per χ 2 test).

Among 52 patients, 4 had associated PVD and were undergoing conservative management as per the advice of the vascular surgeon. Two of these patients were in the test group, and 2 were in the control group.

Wound severity was measured using the PUSH tool. Before intervention, the mean wound score was 14.42 in the test group and 14.27 in the control group, which was statistically comparable. Before intervention, the mean wound size was 54.85 cm2 ± 47 in the test group and 39.38 cm2 ± 17.58 in the control group (P =.016). At week 6, the mean wound size had decreased to 25.08 cm2 ± 39.29 in the test group and 28.69 cm2 ± 17.56 in the control group (P =.617). At week 12, the mean wound size had further reduced to 9.08 cm2 ± 27.62 in the test group and 27.68 cm2 ± 16.88 in the control group (P =.001) (graphical representation is shown in Figure 1).

Figure 1.

Mean ulcer size from before intervention through week 12.

At week 6, there was a 54.50% reduction in mean wound size observed in the test group, and a 27.14% reduction in mean wound size noted in the control group. At week 12, the reduction in mean wound size was 83.44% in the test group and 29.68% in the control group compared with the preintervention wound size (Figure 2, Figure 3).

Figure 2.

Time to wound healing.
Abbreviation: Wk, week

Figure 3.

Time to wound healing.
Abbreviation: Wk, week

Complete wound healing was achieved in 22 of 26 patients (84.61%) in the test group and 14 of 26 patients (53.84%) in the control group during the 12-week study period. The mean time to heal was 6.22 weeks in the test group.

The mean number of hospital visits was 9.2 in the test group and 11.07 in the control group. Four patients in the test group required more than 12 visits (15.38%), and 13 patients in the control group required more than 12 visits (46.15%).

The total cost of the intervention was less than 15 000 INR ($198 US) for 11 patients in the test group and 9 in the control group, 15 000 INR ($198 US) to 30 000 INR ($397 US) for 9 patients in the test group and 5 in the control group, and more than 30 000 INR ($397 US) for 6 patients in the test group and 12 in the control group (P =.001 [Fisher exact test]).

The final outcome of complete wound healing was achieved in 22 wounds in the test group and 14 wounds in the control group (84.61% and 53.84%, respectively) (Figure 4). Among the remaining wounds, 1 resulted in amputation in the test group, whereas 3 in the control group underwent amputation. During the 12-week study period, 3 wounds in the test group did not heal, and 9 wounds in the control group did not heal (P =.009 [Fisher exact test]).

Figure 4.

Final outcome of the wound.

Figure 5.

Technique of ultrathin skin grafting using the Watson modification of the Humby knife.

Figure 6.

(A) Ultrathin skin graft, demonstrating its transparency. (B) Split-thickness skin graft.

Figure 7.

Analysis of wound size and granulation tissue using the chosen software on photographs of (A) granulation tissue and (B) wound dimension.

Figure 8.

Hematoxylin-eosin stain used with 100× magnification. (A) Microscopic image of ultrathin skin graft demonstrates absence of dermis. (B) Microscopic image of split-thickness graft with dermis layer. Source: Department of Pathology, St. Martha's Hospital, Bangalore, India

Complete graft loss was noted in 2 patients, which was expected owing to association with PVD. However, in these cases, the present authors observed clinical signs of wound healing (ie, increased granulation tissue and hyperemia), which allowed repeat grafting with STSG. Later wounds healed completely without any complications. From the results of the current study, the ultrathin graft did not persist in the wounds but seemed to have a long-term effect on tissue regeneration. It appears the ultrathin graft is essential for initiating tissue repair but is dispensable after the patient's cells are activated.

No significant complications were noted at the graft harvest site wound. Two patients had delayed spontaneous healing.

Histopathologic examination of a wound bed tissue biopsy taken before intervention and 3 weeks after UTSG showed a comparative increase in granulation tissue and tiny blood vessels in the test group (Figures 9–17).

Figure 9.

(A) Photomicrograph with hematoxylin-eosin stain with magnification of 100× of wound bed biopsy after the first debridement but before ultrathin skin grafting (UTSG). A solid arrow points to the tiny blood vessels. (B) Photomicrograph of wound bed biopsy 3 weeks after ultrathin skin grafting demonstrated signs of wound healing (ie, increased number of tiny blood vessels and granulation tissue).

Figure 10.

Case 1: (A) a 51-year-old female presented with a nonhealing wound following second toe disarticulation performed 40 days previously to manage a diabetic foot ulcer. The authors performed debridement and ultrathin skin grafting in the same session. (B) At week 2, granulation tissue and hyperemia were evident at the wound site. (C) Complete wound healing was achieved by week 6.
Abbreviations: PO, postoperative; wk, week

Figure 11.

Case 2: (A) a 48-year-old male referred by a general surgeon for wound coverage after disarticulation of the great toe 2 weeks prior for diabetic foot. This patient underwent intervention in the test group. (B) Photograph taken 2 weeks after ultrathin skin grafting demonstrates the graft in situ with a good amount of granulation tissue. The patient was followed on a weekly basis, and (C) complete wound healing was achieved within 6 weeks.
Abbreviations: PO, postoperative; wk, week

Figure 12.

Case 3: a 76-year-old male presented with diabetic foot ulcer over the lateral border of the left foot of 1-month duration. A black patch was present over the ulcer. Debridement and ultrathin skin grafting were performed. (A) Postoperative (PO) week 1 shows the wound covered with ultrathin skin (B) Presence of granulation tissue at week 2. (C) Complete wound healing was achieved by week 3.

Figure 13.

Case 4: a 59-year-old female who 1 month previously had undergone debridement and disarticulation of the fourth toe of the left foot at a local hospital to manage diabetic foot. At presentation to the authors' department the wound was covered with slough. Appearance after (A) debridement and (B) ultrathin skin grafting. (C) Complete wound healing was achieved by week 6.
Abbreviations: PO, postoperative; UTSG, ultrathin skin grafting; wk, week

Figure 14.

Case 10: a 65-year-old male with a history of trophic ulcer of the plantar aspect of the right foot of 2 months' duration. Debridement of a nonhealing wound with moderate slough in situ was done at a local hospital. The appearance of the wound site after (A) debridement and (B) UTSG. (C) Wound healing was achieved by week 7.
Abbreviations: PO, postoperative; UTSG, ultrathin skin grafting; wk, week

Figure 15.

Case 6: a 60-year-old female with diabetes and associated mild peripheral vascular disease for which she was undergoing conservative treatment; she also had a history of diabetic foot ulcer on the plantar aspect of the right foot of 2 months' duration. The patient underwent debridement at a local hospital followed by regular dressing changes. (A) The patient presented to the department with moderate slough and a pale wound bed, which suggested lack of improvement. She underwent debridement and ultrathin skin grafting. (B) Appearance of the graft in situ 1 week after treatment. (C) By week 3 the graft was no longer visible and considerable improvement of the wound bed was evident, with a good amount of granulation tissue and hyperemia suggestive of an enhanced healing process. The patient underwent repeat grafting with STSG. (D) Complete wound healing was achieved by week 8.
Abbreviations: OP, operation; PO, postoperative; STSG, split-thickness skin graft; wk, week

Figure 16.

Case 7: an 80-year-old female with diabetes and associated peripheral vascular disease who was undergoing conservative treatment as well as having undergone debridement and disarticulation of the first 3 toes of the right foot in the general surgery department for a diabetic foot 10 days previously and was referred for wound coverage. (A) At presentation, appearance of a pale wound bed with multiple black patches in between and minimal slough in situ. Debridement and ultrathin skin grafting were performed. (B) The wound covered with ultrathin skin graft. (C) Photograph taken at week 1 demonstrates partial loss of graft. (D) By week 2 complete graft loss is evident, along with drastic improvement at the wound bed, with a good amount of granulation tissue and hyperemia bed. At the time of this writing, repeat grafting for definitive wound closure was planned.
Abbreviations: PO, postoperative; wk, week

Figure 17.

Case 9: a 55-year-old male with a history of multiple debridements as well as great toe disarticulation of the right foot presented with a diabetic foot ulcer. He was referred to plastic surgery after exhibiting no signs of wound healing. A pale wound bed with moderate slough in situ was observed on presentation to the authors' department. (A) Appearance after debridement at the authors' institution. Ultrathin skin grafting was performed next (not shown), and the patient was evaluated weekly, at which time dressings were changed as well in outpatient department. Complete wound closure was achieved in 8 weeks. (B) Appearance of the wound at week 10.
Abbreviations: PO, postoperative; wk, week

processing....