Do Functional Keratin Dressings Accelerate Epithelialization in Human Partial Thickness Wounds? A Randomized Controlled Trial on Skin Graft Donor Sites

METHODS

RESULTS

Thirty-seven patients were enrolled into the study. There were no adverse events relating to either Treatment or Control dressing. Eleven patients were not able to be assessed on postoperative day 7 leaving 26 participants available for analysis, 15 were older than 50 years (median age = 73 years) and 11 were 50 years old or younger (median age = 35). Reasons for not completing assessment were as follows: did not attend follow-up clinic (5), attended clinic too late to be included in assessment (2), dressings changed early by on-ward nursing staff (2), and incomplete consent process (2).

Percentage of epithelization varied markedly across the patients overall. This difference was predominantly associated with age (see Table 1 and Fig 1). In the older (>50 years) group, the majority of each wound was unhealed (median epithelialization percentage, 5%). In this group, there was a significant (P = .023) difference between the epithelialization in the Control portion and the Treatment portion of the wound. The corresponding medians of the Control group and Treatment group were 5% and 10% epithelialization, respectively.

Figure 1. Difference in epithelialization of adjacent sides of donor site wound Treatment vs Control.

In the younger (≤50 years) group, epithelization was almost complete at 7 days (median epithelialization percentage, 80%). There was no significant difference between Treatment and Control portions of the wound.

Figure 1 shows the difference in epithelialization, approximately 7 days after surgery, for all patients measured. This illustrates the difference between the responses of older (>50 years) to younger (≤50 years) patients. Figure 2 shows a typical outcome for the older group: side “A” (Treatment) shows early epithelialization from the epidermal appendages (5% epithelialization) whereas side “B” (Control) has not started to epithelize (0% epithelialization). The Treatment side demonstrates coagulated blood on the surface of the wound as the Treatment dressing is not designed to be hemostatic (unlike the Control dressing). The wound was gently washed with normal saline and adherent slough or blood indicated that the region had not epithelialized; this was taken into account by the blinded assessor.

Figure 2. Photograph showing epithelialization of a typical donor site 7 days after surgery.

Qualitatively, the Treatment dressing was observed to handle the high exudate load during the first 2 days from the donor sites well. Sixteen of 27 patients followed up had questionnaires completed by nurses of which 6 felt that the side-allocated Treatment dressing was less painful to remove, one found the Control dressing side less painful, and the rest noted no difference. Subjectively nurses typically commented that the Treatment dressings were easier, less painful, and less traumatic to remove than the Algisite.

DISCUSSION

Older patients healed their partial-thickness wounds more slowly; however, there was significantly more epithelialization after 7 days in wound portions treated with the keratin-based dressing compared with standard care. This implies that the time to complete epithelialization may be reduced in the portion of the wound treated with the keratin-based dressing, for the older patients. This study also demonstrated rapid epithelialization of split skin graft donor sites in young patients. This is consistent with previous reports¹⁵ and reflects ideal wound healing. There was no significant difference in epithelization rates between Treatment and Control dressings for younger patients.

Delayed epithelialization is commonly caused by both patient factors (age and comorbidities) and wound factors (deep partial-thickness injuries including deep dermal burns) and is associated with wound complications such as infection and scarring.¹⁶ Thus, mitigation of delayed epithelialization is of clinical significance and the results suggest that keratin-based dressings can achieve this in some cases. The clinical implications of this study are that keratin-based dressings can reduce the delayed epithelialization seen in predisposed patients and so reduce the complications of healing in this group of patients. The results may extrapolate from these traumatic, acute partial-thickness wounds to thermal, acute partial-thickness wounds such as burns.

The results of this study are consistent with the proposed mechanism of action and with earlier published preclinical results and other clinical studies. The proposed mechanism, as described in the “Introduction,” is that the exogenous keratin can stimulate keratinocytes via the Akt/mTOR signalling pathway. The clinical observations in this study are consistent with such stimulated keratinocyte activity. However, ethical considerations did not permit biopsy to permit investigation of the response to the Treatment at a cellular level. Furthermore, both preclinical animal studies⁵ and other clinical studies^6-8 showed similar increases in epithelialization rates and are consistent with the findings of this study.

Questionnaires, completed by nurses, indicated that the Treatment dressing was well tolerated by patients, and ease of removal was at least comparable to current standard care. Although there was more coagulated blood on the surface of the Treatment side of wounds, this does not seem to have adversely affected the ease of dressing removal or the rate of epithelialization and healing.

Potential criticism of this study includes the small sample size, especially given the heterogeneity of this patient population. However, the use of internal controls meant that we were able to detect significant difference between Treatment and Control dressings. The wide range of epithelialization rates observed in this study supports using internal controls in the investigation of partial-thickness wound healing rates. The method of assessment, estimation of percentage of epithelialization by a skilled, blinded assessor, is novel. As expected, the neoepithelium was observed to be in patches around the epidermal appendages and the visual assessment method was found to be appropriate to estimate the percentage epithelialization. A weakness of the assessment technique is that it is difficult to repeat, the skilled assessor was confident in his ability to assess “in the flesh” but the digital images were unable to capture detail necessary to make the assessments of percentage epithelialization and hence assessments from the digital images are not reproducible.

Ideally, time to complete epithelialization could be measured for each patient, but a method that observes the wounds daily as they near complete epithelialization is onerous and disruptive for patient's healing. Thus, this method of a single observation at 7 days was used. We suggest that there will be a strong, direct relationship between the percentage epithelialization after 7 days and time to complete epithelialization.

CONCLUSIONS

Keratin-based dressings significantly increase the rate of epithelialization of acute, traumatic partial-thickness wounds in older patients. We suggest that they may be clinically useful in similar situations where epithelialization may be delayed because of patient or wound characteristics.