Epidermal graft encourages wound healing by down-regulation of gap junctional protein and activation of wound bed without graft integration as opposed to split-thickness skin graft.

Wound coverage by split-thickness skin graft (SSG) and epidermal graft (EG) shortens healing time, with comparable outcomes. However, the healing mechanism of EG is not as well understood as SSG. The difference in the healing mechanisms of EG and SSG was investigated using gap junctional proteins, proliferative marker, and cytokeratin markers. Paired punch biopsies were taken from the wound edge and wound bed from patients undergoing EG and SSG at weeks 0 and 1 to investigate wound edge keratinocyte migratory activities (connexins 43, 30, and 26), wound bed activation (Ki67), and the presence of graft integration to the wound bed (cytokeratins 14 and 6). Twenty-four paired biopsies were taken at weeks 0 and 1 (EG, n = 12; SSG, n = 12). Wound edge biopsies demonstrated down-regulation of connexins 43 (P = .023) and 30 (P = .027) after EG, indicating accelerated healing from the wound edge. At week 1, increased expression of Ki67 (P < .05) was seen after EG, indicating activation of cells within the wound bed. Keratinocytes expressing cytokeratins 6 and 14 were observed on all wounds treated with SSG but were absent at week 1 after EG, indicating the absence of graft integration following EG. Despite EG and SSG both being autologous skin grafts, they demonstrate different mechanisms of wound healing. EG accelerates wound healing from the wound edges and activates the wound bed despite not integrating into the wound bed at week 1 post-grafting as opposed to SSG, hence demonstrating properties comparable with a bioactive dressing instead of a skin substitute.

Comparative study on the donor site aesthetic outcome between epidermal graft and split-thickness skin graft.

Donor site aesthetic outcomes of epidermal graft (EG) vs split-thickness skin graft (SSG) have yet to be objectively compared. Here, we evaluate donor site healing using a validated scar assessment tool and digital colorimetric technique, which compares colour in a consistent and objective manner. Ten patients (SSG (n = 5) and EG (n = 5)) were included. Donor site scarring was evaluated using the Vancouver Scar Scale (VSS) at Week 6 and Month 3. Colorimetric measurement was performed at Weeks 3 and 6 and Month 3. The mean donor site healing time for EG was significantly shorter (EG: 4.6 days (95% c.i. 3.8-5.3), SSG: 16.8 days (95% c.i. 13.3-20.1) (P = 0.003)). The VSS scores of the EG donor site were lower at Week 6 and Month 3(P < 0.001). The colour match between the donor site and surrounding skin for EG was better compared with SSG at all time points and was almost identical to their surrounding healthy skin at Month 3. This study is the first to objectively measure the clinical appearance of the EG donor site against SSG. EG donor site has faster healing with excellent scarring and good colour match with its surrounding normal skin at all time points compared with SSG.

A prospective, multicentre study on the use of epidermal grafts to optimise outpatient wound management.

Current wound management through the use of a split-thickness skin graft often requires hospital admission, a period of immobility, attentive donor site wound care and pain management. This study evaluates the feasibility of using a novel epidermal graft-harvesting device (CelluTome) that allows pain-free epidermal skin grafting in the outpatient clinic setting. A prospective series of 35 patients was performed in 2 centres, involving 10 acute and 25 chronic wounds. All patients were subjected to epidermal grafting in the outpatient specialist clinic, without the use of anaesthesia, and allowed to return home after the procedure. Completely healed wounds were noted in 22 patients (62·9%). The overall mean time for 50% and 100% reduction in wound size was 3·31 ± 2·33 and 5·91 ± 3·48 weeks, respectively. There was no significant difference in healing times between the acute and chronic wounds (50% reduction in wound size; acute 2·20 ± 0·91 weeks versus chronic 3·73 ± 2·63 weeks, P = 0·171. Hundred percent reduction in wound size; acute 4·80 ± 1·61 weeks versus chronic 6·83 ± 4·47 weeks, P = 0·183). The mean time for donor site healing was 5·49 ± 1·48 days. The mean pain score during graft harvest was 1·42 ± 0·95, and the donor site Vancouver Scar Scale was 0 for all cases at 6 weeks. This automated device offers autologous skin harvesting in the outpatient setting with minimal or no pain and a scar free donor site, equally benefiting both the acute and chronic wounds. It has the potential to save NHS resources by eliminating the need for theatre space and a hospital bed while at the same time benefiting patient care.

Epidermal grafting for wound healing: a review on the harvesting systems, the ultrastructure of the graft and the mechanism of wound healing.

Epidermal grafting for wound healing involves the transfer of the epidermis from a healthy location to cover a wound. The structural difference of the epidermal graft in comparison to the split-thickness skin graft and full-thickness skin graft contributes to the mechanism of effect. While skin grafting is an epidermal transfer, little is known about the precise mechanism of wound healing by epidermal graft. This paper aims to explore the evolution of the epidermal graft harvesting system over the last five decades, the structural advantages of epidermal graft for wound healing and the current hypotheses on the mechanism of wound healing by epidermal graft. Three mechanisms are proposed: keratinocyte activation, growth factor secretion and reepithelialisation from the wound edge. We evaluate and explain how these processes work and integrate to promote wound healing based on the current in vivo and in vitro evidence. We also review the ongoing clinical trials evaluating the efficacy of epidermal graft for wound healing. The epidermal graft is a promising alternative to the more invasive conventional surgical techniques as it is simple, less expensive and reduces the surgical burden for patients in need of wound coverage.

Systematic review and meta-analysis of the efficacy of epidermal grafting for wound healing.

Autologous skin grafting is an important method for wound coverage; however, it is an invasive procedure and can cause donor site morbidity. Epidermal grafting (EG) enables epidermal transfer to wounds with minimal donor site morbidity. However, data to date have been heterogeneous. This study aims to synthesise the current evidence on EG for wound healing to establish the efficacy of this surgical technique. A comprehensive search in the MEDLINE, EMBASE and CENTRAL databases was conducted. The endpoints assessed were proportion of wounds healed and mean wound-healing time. This systematic review was conducted and reported according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We identified 1568 articles, of which seven articles were included in this review - a total of 209 wounds in 190 patients. The mean wound duration was 17·06 weeks (95% CI 8·57-25·55). Of these, 71·5% (95% CI 56·7-84·2) of the wounds achieved complete healing. Mean time for complete wound healing was 5·53 weeks (95% CI 3·18-7·88). The mean donor site healing time was 7·48 days (95% CI 4·83-10·13), with no reported donor site morbidity. The current data are small and lack level 1 evidence.

A self-controlled comparative study of mini punch graft versus suction blister epidermal graft in the treatment of stable vitiligo.

BACKGROUND: Mini punch graft (MPG) and suction blister epidermal graft (SBEG) are both effective for stable vitiligo, but there is a lack of self-controlled comparison between these two procedures. OBJECTIVE: To compare the efficacy and safety of MPG and SBEG in stable vitiligo. MATERIALS AND METHODS: Twenty-three patients were enrolled in this study. A single white patch from each patient was divided into two halves, one half was treated by MPG, while the other half was treated by SBEG (blister or dermabrasion for recipient site), followed by narrow-band UVB irradiation twice a week for 3 months. The repigmentation rate, relative melanin index (RMI), and relative erythema index (REI) were measured at different time points. RESULTS: The repigmentation rate of grafts was 98.7% (312/316) in MPG, 98% (49/50) in SBEG (blister for recipient site) and 99.3% (272/274) in SBEG (dermabrasion for recipient site). The RMI and REI at different time points had no statistical difference between MPG and SBEG. Cobblestone appearance was the predominant complication in SBEG. For MPG, superficial scar occurred in two cases in recipient sites and no obvious side effects in donor sites. CONCLUSIONS: MPG is much easier, faster with less side effects in donor site.

Generation of Epidermal Equivalents from Hair Follicle Melanocytes, Keratinocytes, and Dermal Fibroblasts.

Bench-to-bedside axis of therapeutic product development is currently being oriented towards minimum invasiveness on both ends-not only clinical application but harvesting of the starting biological material as well. This is particularly relevant for Advanced Therapy Medicinal Products and their specific legislative requirements, even more so in skin regeneration. It is precisely the skin equivalents and grafts that benefit from the minimum-to-noninvasive approach to a noteworthy extent, taking in account the sensitive nature of both skin harvesting and grafting.This chapter includes protocols for two separate steps of generating skin equivalent from the cells cultured from hair follicle outer root sheath. The first step is a non-pigmented epidermal equivalent generated from human keratinocytes from the outer root sheath named non-pigmented epidermal graft. The second step consists of co-cultivating human keratinocytes and human melanocytes from the outer root sheath, hereby producing a pigmented epidermal graft.

Lower donor site morbidity and higher patient satisfaction with epidermal grafting in comparison to split thickness skin grafting: A randomized controlled trial (EPIGRAAFT Trial).

BACKGROUND: Split thickness skin grafting (SSG) is an important modality for wound coverage; however, it leads to donor site morbidity. Epidermal grafting (EG) is a promising option for autologous skin grafting which offers minimal donor site morbidity, though it is not known if EG is an effective clinical alternative for SSG. This study compared the efficacy of EG as an alternative to SSG in terms of wound healing outcomes, donor site morbidity, patient satisfaction and adverse events. METHODS: EPIGRAAFT is a Phase 2, randomized, open-label trial with two parallel groups: EG and SSG. Patients referred for skin grafting with a healthy granulating wound bed were included. The co-primary endpoints were the proportion of wounds healed and donor site healing time. The secondary endpoints include donor site morbidity measured using Vancouver Scar Scale, mean time for complete wound healing, patient satisfaction assessed using a validated skin grafting questionnaire and incidence of adverse events. RESULTS: Of the 61 patients screened, 44 patients were randomized. There was no difference in the proportion of wounds healed at 6 weeks (p=0.366) and 3 months(p=0.24) as well as the mean time for wound healing (p=0.12). EG resulted in lower donor site morbidity (p=0.001), faster donor site healing time (EG: 4.86 days vs. SSG: 21.32 days) (p<0.0001), and higher overall satisfaction (p<0.001). There were no adverse events reported. CONCLUSION: This study demonstrated that EG has superior donor site outcomes with faster donor site healing and lower morbidity compared to SSG, while having comparable wound healing outcomes. Patients receiving EG also experienced higher donor site satisfaction compared to SSG. ClinicalTrials.gov identifier: NCT02535481.

Epidermal grafting versus split-thickness skin grafting for wound healing (EPIGRAAFT): study protocol for a randomised controlled trial.

BACKGROUND: Split-thickness skin grafting (SSG) is an important modality for wound closure. However, the donor site becomes a second, often painful wound, which may take more time to heal than the graft site itself and holds the risk of infection and scarring. Epidermal grafting (EG) is an alternative method of autologous skin grafting that harvests only the epidermal layer of the skin by applying continuous negative pressure on the normal skin to raise blisters. This procedure has minimal donor site morbidity and is relatively pain-free, allowing autologous skin grafting in an outpatient setting. We plan to compare EG to SSG and to further investigate the cellular mechanism by which each technique achieves wound healing. METHODS/DESIGN: EPIGRAAFT is a multicentre, randomised, controlled trial that compares the efficacy and wound-healing mechanism of EG with SSG for wound healing. The primary outcome measures are the proportion of wounds healed in 6 weeks and the donor site healing time. The secondary outcome measures include the mean time for complete wound healing, pain score, patient satisfaction, health care utilisation, cost analysis, and incidence of adverse events. DISCUSSION: This study is expected to define the efficacy of EG and promote further understanding of the mechanism of wound healing by EG compared to SSG. The results of this study can be used to inform the current best practise for wound care. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT02535481 . Registered on 11 August 2015.

Protocol for a systematic review of the efficacy of epidermal grafting for wound healing.

BACKGROUND: Autologous skin grafting is an important modality for wound coverage; however, it can result in donor site morbidity. Epidermal grafting is an emerging option to overcome this challenge. Furthermore, it can be done in an outpatient setting with minimal or no pain. To date, the evidence on the efficacy of this technique for wound healing has yet to be outlined. We aim to synthesise the current evidence on epidermal grafting for wound healing to establish the efficacy of this technique. METHODS/DESIGN: We will conduct a comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases (up to May 2016) to identify studies on epidermal grafting for wound healing. We will include any primary studies (excluding case reports or case series lesser than three patients) or systematic reviews of such studies to assess the outcome of epidermal grafting for wound healing either on its own or compared to other methods. The expected primary outcome measures are the efficacy of epidermal grafting for wound healing (measured by the proportion of wounds healed at 6 weeks) and the mean wound-healing time (time for complete re-epithelialisation). Secondary outcome measures are the mean donor site-healing time, need for anaesthesia, costs associated with resource use, health-related quality of life, and proportion of patients with adverse event. Subgroup analysis will be performed for the proportions of wounds healed based on wound aetiology. DISCUSSION: This is a timely systematic review, and the finding of this systematic review is expected to guide research and clinical practice aimed at improving wound care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033051.