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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 28  |  Issue : 4  |  Page : 231-236

Medical and cosmeceutical applications for enhancement of partial-thickness skin graft donor-site healing


1 Department of Plastic Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey
2 Department of Pharmaceutical Technology, Subdivision of Cosmetology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

Date of Submission10-Jul-2019
Date of Acceptance07-Nov-2019
Date of Web Publication28-Sep-2020

Correspondence Address:
Dr. Galip Gencay Ustun
Department of Plastic Surgery, Hacettepe University, Faculty of Medicine, Hacettepe Universitesi Hastaneleri Plastik Cerrahi Anabilim Dal. Sekreterli.i, 06100, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjps.tjps_61_19

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  Abstract 


Introduction: After partial-thickness skin graft (PTSG) harvesting, a dermal surface is exposed and an iatrogenic wound is created. Application of various agents has been studied for enhancement of healing process in PTSG donor area. The ideal agent should accelerate healing, provide comfort to the patient, not allow infection, and be easily applicable and cheap. Materials and Methods: The Cochrane Central Register of Controlled Trials, PubMed, Scopus. and EMBASE databases were screened for words (“skin graft” + “donor”), by using time limits between 1989 and 2018. This study involved a total of 5 systematic reviews and 43 original articles which met the inclusion criteria. Articles were reviewed and parameters such as healing time, pain, infection rate, cosmetic result, and cost were extracted. Results: Systematic reviews favor moist dressing materials over dry ones considering healing time and patient comfort. Hydrocolloids provide rapid wound healing, and dressing changes do not cause any disruption to the newly regenerated epithelium. Alginates seem to have a longer healing time than hydrocolloid materials. Polyurethane films are characterized by rapid epithelialization and painless monitoring as well as low costs. The epithelialization time of MEBO®, a cosmeceutical product, is reported to be faster than polyurethane films. Local and systemic drug applications warrant further research before routine clinical usage. Conclusion: Dressing materials are the most commonly used and appropriate group according to the studies performed to date. It is seen that moist dressing materials are more favorable. Although there is not a subgroup with a clear superiority, it can be seen that the hydrofiber and polyurethane film groups are one step ahead in terms of ease of use, patient comfort, epithelialization speed, and scar quality. Polyurethane films have a cost advantage to the hydrofiber group.

Keywords: Cosmeceuticals, donor area, dressing materials, epithelialization, partial thickness skin graft, wound care


How to cite this article:
Ustun GG, Ozgur F, Hekimoglu S. Medical and cosmeceutical applications for enhancement of partial-thickness skin graft donor-site healing. Turk J Plast Surg 2020;28:231-6

How to cite this URL:
Ustun GG, Ozgur F, Hekimoglu S. Medical and cosmeceutical applications for enhancement of partial-thickness skin graft donor-site healing. Turk J Plast Surg [serial online] 2020 [cited 2020 Oct 29];28:231-6. Available from: http://www.turkjplastsurg.org/text.asp?2020/28/4/231/296470




  Introduction Top


Even with all the advancement in our technique and today's technology, skin grafting, introduced two centuries ago, is still a precious weapon in our armamentarium for reconstruction of skin defects caused by burns, trauma, or cancer surgery.[1],[2] Skin grafts can be classified according to the amount of dermis they contain, as partial- or full-thickness skin grafts. Partial-thickness skin grafts (PTSGs) have numerous advantages and disadvantages. Advantages include a vast amount of donor area and the option to use same donor site over and over again after proper reepithelialization periods. Both of these advantages make this tool an invaluable option for the patient that has extensive skin defects, frequently caused by burns. In terms of disadvantages, in addition to secondary contraction, pigmentation and poor cosmetic results, donor-site morbidity is a serious limitation. After graft harvesting, a dermal surface is exposed and an iatrogenic wound is created. Evidence shows this wound causes more complaints than the recipient area.[3],[4] To keep these complaints to a minimum, and to use the same area repeatedly in a short period for patient in need, fast and high-quality healing is required.

Application of various agents has been studied for enhancement of healing process in PTSG donor area. The ideal agent should accelerate healing, provide comfort to the patient, not allow infection, be easily applicable, and cheap.[5] Wound dressings, topical/systemic drugs, various herbal extracts, and other products have been proposed for enhancement of healing of donor area. A comprehensive review of these agents is aimed.


  Materials and Methods Top


The Cochrane Central Register of Controlled Trials, PubMed, Scopus, and EMBASE databases were screened for words (“skin graft” + “donor”), by using time limits between 1989 and 2018. After removal of duplicates, abstracts were reviewed by authors. Non-English language articles, articles without an available full-text, case reports, and letters to the editor were excluded from the study. This study involved a total of 5 systematic reviews and 43 original articles which met the inclusion criteria. Articles were reviewed and parameters such as healing time, pain, infection rate, cosmetic result, and cost were extracted.


  Results Top


To facilitate understanding, agents were grouped into five categories; (1) wound dressings, (2) systemically applied drugs, (3) topically applied drugs, (4) cosmeceutical products, and (5) other products.

Wound dressings

Although studies on many different types of agents have been conducted, current literature is mostly concentrated on dressing materials. Looking at the number of publications published every year on the subject, since the early 1980s, one or two publications studying a dressing material have been published each year.[5]

Superiority of a singular dressing material has been discussed separately by independent studies. However, categorization of dressing materials with clear borders is difficult. Interpretation of methodology of systematic reviews shows comparison is made using two main categories: moist (Opsite®, Allevyn®, Aquacel®, Kaltostat®, etc.) and dry (Xeroform®, Jelonet®, etc.) dressings. In Rakel's early work,[6] without using moist/ dry categorization, 33 articles were included, and transparent film (polyurethane) was found to be the most successful in terms of patient comfort, infection rate, healing rate, and cost. In the second, Wiechula[7] combined 58 separate studies, stated that the moist dressing materials had faster healing, less pain, and lower infection rates. Voineskos et al.[5] grouped the studies according to pain, rate of infection, healing rate, quality of life, and cost. They stated that moist dressing materials are more advantageous in terms of pain, and there is no difference between infection rates and wound healing. It was found that dry dressing materials seem to be cheaper.[5] Brown and Holloway's review[8] showed moist dressing materials have the advantage of pain relief and healing rate. They stated that combination of more than one primary dressing material should be considered. Latest review is Serebrakian et al.'s,[9] which uses a similar time span and inclusion criteria with Brown's and Holloway work,[8] and also has compatible results with it.

This study also emphasizes the lack of standardization problem with ongoing studies in the literature.

These reviews take root from independent articles studying individual dressing materials. Most common dressing materials studied in the literature are as follows.

Dry wound dressings

Xeroform®

Xeroform® is a sterile, fine-dressed gauze dressing material that is impregnated with petrolatum. It contains 3% bismuth tribromofenamate and has bacteriostatic effect. It can be used in mild exudate wounds. Failure to adhere to the wound is a feature that increases patient comfort according to the manufacturer. However, low patient comfort due to higher pain scores has been reported.[10]

Jelonet®

This product is obtained by impregnation of paraffin into a leno braided fabric. The purpose of paraffin is to prevent adhesion to the wound. Malpass et al.'s work[11] shows epithelialization time was 10.4 ± 2.6 days for Xeroform® and 10.5 ± 2.7 days for Jelonet® (P = 0.84). The authors concluded Xeroform® is preferred due to patient comfort.

Bactigras®

It is produced by impregnation of paraffin and additionally 0.5% chlorhexidine acetate in a leno-braided fabric. Chlorhexidine is an effective antibacterial to Gram-positive/negatives.[12] Cost-effectiveness is reported.[13] However, in the study comparing five different dressing materials, Demirtas et al.[14] concluded Bactigras® is the easiest to use dressing material, yet, it also has the highest infection rate, lowest reepithelialization rate, and highest pain scores among Comfeel®, Aquacel®, Opsite®, and Adaptic®.

Moist wound dressings

Duoderm®, Comfeel Plus®

Hydrocolloids gave promising results to other dressing materials in many studies.[14],[15],[16],[17],[18],[19] According to these studies, hydrocolloids provide rapid wound healing, and dressing changes do not cause any disruption to the newly regenerated epithelium. The disadvantage is the leakage and smell from the edge of the dressing. Wiechula' s review[7] stated although hydrocolloids had superiority over dry dressing materials in terms of pain, infection rate, and recovery time, same superiority could not be shown against other moist dressing materials.

Aquacel® is included in the hydrofiber group, which can also be evaluated as a subgroup of hydrocolloids. Its structure enables collecting and gel the excess exudate while maintaining the proper moisture for wound healing. Air permeability is also stated by the manufacturer. Main target is better wound healing under exudate control and breathable environment. In many different studies, epithelialization was found to be faster than other materials.[14],[20],[21] A common feature of these studies is that the material is more expensive than all other materials it is compared.[14],[22]

Kaltostat®

It consists of 80:20 combination of sodium and carboxy salts of alginate. It is produced by the method of impregnation of this component to a high absorbent fabric. Alginates absorb exudate and become gel-like in time. It is suggested that the microenvironment formed in the wound contributes to wound healing. The first study on alginates was performed by Attwood[23] reported that the alginates were cheap, hemostasis-providing, comfortable, healing-accelerating materials. Kaltostat® has also been reported to have a faster healing time than Aquacel® and Allevyn®.[24],[25],[26] However, controversy exists. Healing time has also been reported to last longer than hydrocolloid materials.[14],[18] Venstraelen[27] stated that alginates have a drying problem and adhere to the wound surface, and a tendency to  Pseudomonas aeruginosa Scientific Name Search fection has been observed in wounds.

Allevyn®

This product, which is obtained by combining hydrophilic polyurethane foam with a semi-permeable polyurethane film, also has the ability to breathe with exudate absorption.

Acticoat®

Acticoat is the most widely known product of preparations containing silve. Acticoat®, a triple-layer product, contains two layers of silver-impregnated high-density polypropylene and a middle layer made of silk and polyester between these two layers. It is known that impregnated silver nanocrystals have antifungal properties as well as antibacterial effects for Gram-positive and negative bacteria. Because of their antimicrobial effects, silvery materials can be used during wound healing process.[28] Although there are publications about their use in skin graft donor areas, there are contradictory results. Innes et al.[29] found Allevyn® has higher epithelialization scores (P < 0.001) and also is more successful in terms of scar quality. The use of silvery materials was not recommended as a result of the study. In contrast, Argirova et al.[30] compared same two products and Acticoat® was found to provide faster epithelialization and lower pain scores (P = 0.0003 and P = 0.00011, respectively).

Opsite®, Tegaderm®, Omiderm®

It is made of a polyurethane film, with acrylic adhesive on one side providing adhesion. Prevents microbial contamination and also has an occlusive effect which makes it considered as a moist dressing material. These products are characterized by rapid epithelialization and painless monitoring as well as low costs. In their first study, Dornseifer et al.[31] put needle holes on the film 1 cm apart, to provide discharge. Then, covered it with a secondary layer of gauze and waited for 10 days. They had an epithelialization rate of 86.6% on the 10th day. In their next study, this material was compared with Aquacel® on fifty patients, and authors reported statistically significant faster epithelialization and less pain (P < 0.0001).[32] Advantages include ease of use, high patient comfort, and low cost.[33],[34],[35] Combination of Aquacel® (primary dressing) with polyurethane film (secondary dressing) is another concept studied and recommended in the literature.[36]

Systemic drug applications

Growth hormone

Since human growth hormone (hGH) triggers anabolism, increases protein synthesis, and immune capacity, researchers have hypothesized that the same anabolic effect may also be seen in PTSG donor sites.[37],[38] It was observed that the recombinant growth hormone accelerated healing and reduced the length of hospitalization by 25%–30%, but no explanation could be given on the mechanism of action.[39] Yet, contradictory results exist. Losada et al.[40] gave the same dose of hGH to patients with severe burns, and there was no significant effect on recovery and hospitalization time. With contradictory results and side effects such as hyperglycemia, hGH is rarely used in PTSG donor areas.

Arginine

Evidence shows rodents fed poorly from arginine suffer from wound healing problems.[41] Moreover, collagen synthesis and reepithelialization rates are better in rodents given arginine.[42] These findings led to the hypothesis that intravenous arginine supplementation may contribute to the epithelialization of PTSG donor sites. In their independent studies, Li and Debats[43],[44] gave a daily dose of 30 g arginine to human subjects and compared the improvement of graft donor sites with control groups. As result of both studies, there was no positive effect of arginine administration.

Local drug applications

Growth factors

Growth factors have been shown to play an active role in wound healing. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) are agents studied. In a prospective, double-blind, randomized study, 17 healthy volunteers were treated with topical EGF and silver sulfadiazine on skin graft donor areas with PTSG donor site in bilateral thighs. At the end of the study, there was no difference between the two groups.[45] Yet, in another study of 53 patients, Ma et al.[46] reported that topical FGF application accelerated epithelialization in the PTSG donor area and the recovery time was significantly reduced.

Platelet-rich plasma

Platelet-rich plasma (PRP) use on PTSG donor sites was not found to be associated with accelerated epithelialization.[47] Another study showed less pain in patients with PRP gel used topically, but a study reported no outcome regarding epithelialization.[48]

Cosmeceutical products

Moist Exposed Burn Ointment®

MEBO® is an FDA-approved ointment used traditionally for burn injuries, particularly in China. It contains sitosterol, sesame oil, beeswax, and herbal extracts. It has an occlusive effect. In comparison with Tegaderm®, the epithelialization time of MEBO® was found to be 9 days and Tegaderm was 13 days. There was a significant difference between the results of TEWL (Transepidermal water loss) measurement in the same study. Late scar is also considered to be better in MEBO group.[49]

Cybele® Scagel

CS is an ointment containing alliumcepa extract, centellaasiatica extract, aloevera extract, mulberry extract, and nanohydroxypolysilane. Patient satisfaction and scar quality were found to be higher in the group using CS compared to control group.[50]

Other products

Honey

Honey has been shown to have a positive effect on wound healing.[51] Misirlioglu et al.[52] reported honey-impregnated gauze provided faster epithelialization than paraffin and saline-impregnated gauzes and lower pain scores on PTSG donor sites. This condition was attributed to the thought that the hypertonic honey reduces the edema formation and contributes to the wound healing. Subrahmanyam[53] also reported that epithelialization was faster than petroleum jelly-impregnated gases in their own study. However, lack of standardization and sterilization remains as a problem of this agent.

Human amniotic membrane

Loeffelbein et al.[54] compared polyurethane film and human amniotic membrane of PTSG donor sites. There was no difference between two groups in terms of epithelialization. Aesthetic result was better in amniotic membrane group. Salehi et al.[55] compared human amniotic membrane with vaseline ordered gauze and found patient comfort and epithelialization time were more successful in HAM group. In both studies, no information was provided about the cost of the product used.


  Discussion Top


Despite the fact that many researchers have claimed to find a gold standard agent for healing of PTSG donor sites, it is unfortunately not possible to say so, at least yet.

All studies concentrating on PTSG donor-site healing considered, dressing materials seem to be the most remarkable and rapidly developing group. Different companies are presenting dozens of products which show less or more variability from each other. Authors think interpretation of materials in a bottom-up fashion may help the reader and avoid losing path during analysis. Moist/dry dressing selection is the first decision surgeon should make. Although some studies show no difference, most of the literature reveals that moist materials generally appear to be more advantageous in terms of pain relief and epithelialization.[5],[6],[7],[8],[9] When subgroups of moist dressings analyzed, hydrocolloid groups have been shown to be useful in many studies.[15],[17],[18] The hydrofibers, a subgroup of this group, were found to be very successful in terms of epithelialization rate, painless dressing change and protection against infection, aside from the high price disadvantages.[20] Although silvery materials are the most commonly used materials in wound and burn care due to their antibacterial activity, there is no consensus in the literature that the materials containing silver are more successful and the number of studies is insufficient.[30] Polyurethane films have been known for many years but have been revalued in recent years. These materials offer ease of use as well as low cost and high patient comfort. Comparative studies with hydrofiber group showed that they have an advantage of better epithelialization and cost. Considering all of the dressing materials, the authors think polyurethane films and hydrocolloid/hydrofiber group seems to have an advantage over other materials.

Although almost all studies on PTSG donor sites have involved local applications, systemic drug applications have been studied. Systemic growth hormone use can be considered possibly beneficiary, due to contradictory results. However, systemic side effects such as hyperglycemia are inevitable. Routine use of systemic growth hormone, does not seem possible at least in the near future. The utility of intravenous arginine, another systemic application, has not been shown in any study.

FGF and PRP, studied as locally applied drugs, and the products were mentioned to be useful. Despite the promise of both products, the difficulty of acquisition and application appears to be the handicap of both. Higher cost, especially for FGF is another drawback. Even though they accelerate healing, there are no data on their superiority to simple dressing materials.

To define cosmeceutical products, it is necessary to define cosmetic products and drug concepts. Cosmetic products aim to increase the attractiveness “without affecting the structure and function of the skin.” Drugs are preparations used to prevent, diagnose, or treat a disease. Drugs can cause structural and/or functional changes in the organism to, which they are administered, depending on their mechanism of action. Cosmeceutical products are in between these two groups, by changing the structure of the skin “to a certain degree.”[56] MEBO®, the first cosmeceutical product, shown to be beneficial in PTSG donor area healing process. And also, it is the only preparation with the use of TEWL measurement to evaluate cutaneous barrier function. Transepidermal vaporization increases due to loss of epidermal barrier and TEWL increases. As an objective measurement tool, the authors think TEWL measurements, supported by photographical examinations and patient surveys, would increase the validity of studies to be planned.

There are different problems related to honey. The product is not standardized and nonsterile. Sugar content can also accelerate bacterial contamination. The authors think routine use is not possible. The human amniotic membrane is another material that seems quite impossible to use in accordance with ethical concerns and laws. In the related studies, no cost has been stated, and the superiority over a successful dressing material has not been demonstrated.


  Conclusion Top


The quest of searching the gold standard method/agent for PTSG donor sites continues. Dressing materials are the most suitable group according to the studies performed to date. It is seen that moist dressing materials are more favorable. Although there is not a subgroup with a clear superiority, it can be seen that the hydrofiber and polyurethane film groups are one step ahead in terms of ease of use, patient comfort, epithelialization speed, and scar quality. Polyurethane films have a cost advantage to the hydrofiber group.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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