J. Exp. Path. (I990) 71, I55-I70

A controlled model of moist wound healing: comparison between semi-permeable film, antiseptics and sugar paste Helen G. Archer,* Sheila Barnett,t Sarah Irving,t K.R. Middletont and D.V. Seal§ *Infection Control, $Department of Pharmacy and § Department of Microbiology, Northwick Park Hospital, Harrow and t Department of Research in Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK

Received for publication 29 March I 989 Accepted for publication I4 September I 989

Summary. An established wound model in the pig has been modified using a Stomahesive ring to enable study of the effects of fluids used in wound care. Full thickness wounds (up to 9 mm deep) were treated with the substances under test. Each application was held in place with a Stomahesive flange, the inner part ofwhich had been excised as far as the hard plastic ring. All dressings were then covered with OpSite which allowed gaseous exchange whilst retaining treatment fluids and secretions. Wounds were treated immediately and at 2 and 4 days. The experiment was terminated after 7 days and the whole wound, with dressing, was excised for histological examination. The wounds covered with OpSite alone and those treated with sugar paste under Opsite were found to be infilled with granulation tissue over which epidermal migration was taking place. Those wounds which had been packed with gauze, to which had been added one ofthe following: chlorhexidine gluconate 0.2%, Irgasan 0.2%, povidone iodine o.8% or EUSOL half-strength, showed delayed healing in that less infilling had taken place over the same time period. This delay could be attributed to the nature ofthe chemicals used and/or the influence of gauze packing. This delay in the healing of wounds treated with chemical agents was least with EUSOL half-strength and greatest with chlorhexidine. No toxic effects were observed with sugar paste which may be preferable to antiseptics for the management of dirty or infected wounds. Keywords: wounds, healing, model, sugar, antiseptics, dressings, pH

Many new types of dressings such as hydro- Winter and Scales (i963) first showed in a colloids and hydrogels have been introduced pig model that keeping wounds moist in the last few years claiming to provide allowed more rapid epidermal migration at optimal conditions for wound healing (Kick- the same level as the undamaged epidermis hofen et al. I986) but most have not been and without shrinkage. This has been inves- subjected to rigorous controlled trials in tigated further, in superficial wounds in pigs, animals or humans. Winter (I962) and when re-epithelialization was increased

Correspondence: Dr K.R. Middleton, Department of Pharmacy, Northwick Park Hospital, Watford Road, Harrow HAI 3UJ, UK. '55 I5 6 H.G. Archer et al. beneath both oxygen-permeable and imper- Healthcare Group, Oldham; Stomahesive meable occlusive dressings (Alvarez et al. flanges from Squibb Surgicare Ltd, Moreton, I 983). This principle has been developed, for Wirral; OpSite from Smith & Nephew Medi- example with a semi-permeable plastic film cal Ltd, Hull; povidone iodine I0% solution OpSite, although excess exudate tends to from Napp Laboratories Ltd, Cambridge; accumulate under it. Its clinical use has been EUSOL from Macarthys Medical Ltd, Rom- recently reviewed (Alper I986). ford. Chlorhexidine gluconate 0.2% w/v was Sugar paste has been used for over 4 years prepared in the pharmacy at Northwick Park at Northwick Park Hospital and at other by diluting Hibitane Gluconate 20% solution centres in the UK. The thin paste is of similar (ICI, Macclesfield, Cheshire) with water and consistency to thin honey and can be autoclaving at I2I°C for I5 min. Irgasan instilled via a syringe and Kwill (fine plastic DP300 and its diluent (propylene glycol 5% tubing) into abscess cavities with small open- w/v and Empicol LQ33T 33% w/v- ings. Traditionally such wounds are packed monoethanolaminelaurylsulphate, Surfa- with gauze soaked in EUSOL, a treatment chem Ltd) were a gift from Hough Hoseason which is often painful for the patient and & Co Ltd, Manchester. Sugar paste was may be harmful to granulating tissue. Thick manufactured in the pharmacy at North- sugar paste is suitable for packing into large wick Park Hospital to the following formula: open wounds such as pressure sore cavities. Both pastes have excellent antimicrobial Castor sugar I200 g activity in vitro and have provided effective (fine granular sucrose) treatment for infected and malodorous Icing sugar-additive free i8oo g wounds (Middleton & Seal I 985, I 989). (powdered sucrose) Wound healing and orientation of colla- Polyethylene glycol 400 686 ml gen fibres have been extensively studied in Hydrogen peroxide 30% igml the pig (Winter I962; Laufer et al. I974) Final concentration ofhydrogen peroxide which is the most suitable animal to study was O.I5% v/w. full thickness wound healing because the epidermis, dermis and subcutaneous fat resembles the human (Hartwell 1955; Methods Winter I966). We have adapted Winter's Animals and anaesthesia model to study moist wound healing, with sealed chambers placed over each wound Trials were carried out using three o0-I2 and have compared the effects on healing of week female pigs (gilts), weighing approxi- our Northwick Park sugar paste (Middleton mately 27 kg (6o lb). They were housed in & Seal I 98 5), various antiseptics and OpSite individual pens for the whole of the trial alone in a controlled trial. A similar study, including an acclimatization period of 2 comparing calcium alginate fabric with weeks prior to the first operations. Food was OpSite, has been conducted by Barnett and withheld on the morning of operation and Varley (i 987) but sealed chambers were not anaesthesia was induced without exciting used and the OpSite was applied directly to the animal with 4% Halothane, nitrous oxide skin. 4 1/min and oxygen 3 1/min delivered through a conical nose mask. The animal Materials was rendered unconscious in about 4 min. Anaesthesia was maintained with oxygen (3 Halothane was purchased from ICI, Maccles- 1/min), nitrous oxide 4 1/min) and 2.0% field, Cheshire; chlorhexidine gluconate Halothane until the end ofthe operation. The 0.015% w/v and cetrimide 0.15% w/v solu- pig was then carried back to the pen and tion (Tisept) and Tubinette from Seton monitored until regaining consciousness. Effect of dressings on moist wound healing I57 Operative procedure for production of wounds placed over each wound site and the inner circle of Stomahesive cut out as far The hair on the area to be operated on was as the clipped and the skin washed with chlorhexi- hard plastic ring. This yielded an area just sufficient to dine gluconate 0.015%/cetrimide 0.15% expose the wound underneath. solution, shaved and dried. This ensured that With six wounds per flank, arranged as two the dressings adhered. rows of three, the application of the Stoma- hesive flange was such that there was com- plete occlusion of normal skin between and around each wound (Fig. 2). Tests were arranged so that each vertical pair ofwounds contained the same dressing, which ensured that mixing of products did not occur; past experience had shown that any leakage tended to track from the top wound down- wards. After each dressing had been applied, the site was covered with OpSite self-adhe- sive, water-vapour-permeable, polyurethane plastic film. A cotton body stocking of Tubi- nette was put around the pig to help reduce direct rubbing of the dressings in the pen.

Application of wound dressings Six wounds on one side of the first pig were dressed with OpSite, as controls of moist wound healing without gauze. Six wounds on the other side were dressed with North- wick Park sugar paste. For the second and third pigs, four wounds were each dressed with OpSite (controls), Irgasan DP300 (0.2% w/v in diluent), chlor- hexidine gluconate (0.2% W/V), povidine Fig. i. Arrangement of wounds for each pig. iodine o.8% (freshly prepared from a io% commercial preparation with o.9% saline) and EUSOL half-strength (freshly prepared Standard partial thickness wounds were by diluting the full strength preparation with made by placing a Perspex guide (window o.9% saline). Two wounds were each dressed size 2 5 mm square) on the skin so that two of with sugar paste and Irgasan diluent. the sides were parallel to the direction of hair In order to observe healing in the absence growth. Shallow incisions were made to of foreign bodies, OpSite control wounds did delineate the margins of the wound and the not contain gauze. Thick sugar paste was wound guide removed. The blade of a scalpel applied by rolling it into a ball and packing was used to dissect the epidermis and papill- the wound. All other wounds were packed ary layer ofthe dermis over the whole wound with five layers of gauze which had been cut area to a depth of approximately 9 mm. Six to the size of the wound. Five ml of each wounds were made on each side of the antiseptic solution were applied to the gauze animal (Fig. i). A Stomahesive flange was in the wound with a syringe. I5 8 H.G. Archer et al.

Fig. 2. Right flank of pig 3 showing six wound sites after being covered for 48 h with Stomahesive dressings and OpSite plastic film. 3 And 6, chlorhexidine gluconate 0.2% w/v with gauze dressing; 2 and 5, OpSite control without gauze dressing; i and 4, Irgasan diluent with gauze dressing.

Wound care needle for evaluation of antimicrobial acti- Wounds were inspected 48 and 96 h follow- vity and measurement of pH. The exudate ing the initial procedure. Fluid exudate from collected was stored at 40C. pH was deter- each wound was removed as described below mined immediately using a pH meter (Orion and the OpSite was cut around the Stomahe- Research Model 7oIA). sive flange (the hard plastic ring provided an ideal surface for this to be performed). The Termination of experiment and sampling for wounds were re-dressed working from the histological examination top to bottom of a pair so that the same test Seven days after the initial operation each compounds were dealt with sequentially. pig was anaesthetized as described pre- Wounds containing gauze were replenished viously and wound exudate collected. The by injecting 2 ml of each antiseptic into the Stomahesive dressing was removed from one gauze taking care not to disturb it. Wounds side of the pig at a time. Gauze was not containing sugar were repacked with paste. removed prior to biopsy to ensure that tissue OpSite and Tubinette body stocking were was not disturbed. Tissue was dissected to a applied as described above. depth of I2-15 mm and normal skin was removed from around the wound. Sampling from wound site The wound exudate was retained within the Histology Stomahesive flange underneath the OpSite All biopsy specimens were placed immedia- and was removed with a sterile syringe and tely in i o% formal saline and trimmed to size Effect of dressings on moist wound healing I59 after 24 h fixation. Photographs were taken antibacterial activity of exudates collected of all prepared specimens prior to processing. 48 h after application of test substances, and The tissue was embedded using routine wax measured against S. epidermidis,are given in impregnation and serial sections cut at IO Table 3. Irgasan and chlorhexidine gluco- gum on a rotary microtome. Sections were nate retained persistent activity but others stained with Ehrlich's haematoxylin and failed to do so. The pH of wound exudates is eosin and Gram's stains. given in Table 4. Sugar paste treated wounds were acidic (pH 5.5) compared to the OpSite Analysis of antimicrobial activity of wound controls which were slightly alkaline (pH exudates 7.5) and all the other treatment groups which had pH values of 7.0 or greater (Table A laboratory isolate of a commensal Staphy- 4). Sugar paste, at concentrations of io to lococcus epidermidis was inoculated into 50% dissolved in water, has a pH of 4.8. nutrient broth and incubated overnight at 3 7TC. This was flooded onto a 20 cm square plate of nutrient agar which was allowed to OpSite dry. Sixteen wells were made in the agar The six wounds covered with OpSite in the using a cork borer (diameter 7.5 mm). Each first pig were directly comparable with the well was filled with a different wound exu- four OpSite-covered wounds in the second date. The plate was incubated for i 8 h at and third pigs. Seven of ten wounds had 3 70C after which zones of inhibition were infilled to the level of the surrounding skin measured with calipers. while three were 66% infilled. Histology showed well defined connective repair tissue Bacteriological analysis of wound exudates on the same plane as the uninvolved epider- mis, with good epidermal regeneration. The Approximately 30 ul of exudate were spread presence of bacteria on the surface of these on both blood and McConkey agar plates. wounds did not appear to impair healing, These were incubated aerobically at 3 70C for neither were they by h after which colonies were seen Gram stain in the I8 any present connective repair tissue. These wounds were counted and identified by standard methods. considered as controls. Winter has demonstrated in the past that Results an occlusive dressing doubles the rate of re- A epithelialization when compared to wounds typical appearance of the pig model to air wounds enclosed by Stomahesive rings and exposed (Winter I962; Winter & Scales is shown in I963). Prospective clinical trials have been OpSite Fig. 2. Fluid exudate can carried out with OpSite for healing split-skin be clearly seen contained within each wound graft donor sites but, enclosure. None of the wounds appeared although it is permeable infected. to water vapour, haemoserous exudate clinically gathers beneath it, preventing its adoption as Representative transverse sections (x i a standard donor site magnification) ofeach wound treatment at 7 dressing (Richmond & days are illustrated in Figure 3 a-g, together Sutherland I986). with their histology at x 85 (Fig. 4 a-j). Further details are given in Table i, and are discussed below. Sugar paste The bacterial culture results for each Six wounds were packed with sugar paste wound in the second and third pigs are given and covered with OpSite in the first pig and in Table 2; bacteriology was not performed two wounds were similarly treated in the on wound exudate from the first pig. The second pig. Both the latter wounds infilled i6o H.G. Archer et al.

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2N W OFAM M yoF __E2S _ `-~ ; ; g- 1lI7-00 Fig. 4. Histology of pig wounds. x 85. a, OpSite control; epidermal migration over granulation tissue; b, OpSite control; connective tissue repair; c, sugar paste; epidermal migration over granulation tissue; d, sugar paste; connective tissue repair; e, Irgasan diluent; immature granulation tissue around 43, cotton fibres; f, Irgasan 0.2%; immature granulation tissue around &, cotton fibres; g, chlorhexidine 0.2%; lack ofepidermal migration at edge ofwound; h, chlorhexidine 0.2%; immature granulation tissue and lack of new vessel formation; i, Povidone iodine o.8%; maturing granulation tissue; j, EUSOL (half strength); disorganized granulation tissue around 4,, trapped cotton fibres. i62 H.G. Archer et al. Effect of dressings on moist wound healing I63 i64 H.G. Archer et al. EJfect of dressings on moist wound healing I65 I66 H.G. Archer et a]. Table i. Comparison of morphology of wound treatments

Average New Number (%) Epidermal Collagen vessel Gauze of infilling regeneration maturation formation Bacteria present wounds

OpSite go +++ +++ +++ +++ - IO Sugar 87 +++ +++ +++ +++ - 8 Irgasan base 63 + + + + + + + + + + 2 Irgasan 63 + +/+ + + + + + + 4 Chlorhexidine 25 +/- +/- +/- - + 4 Povidone iodine 83 + + + + ++ + +++ + 4 EUSOL (half strength) go + + + + ++ + +++ + 4

- to + + + represents increasing prevalence.

Table 2. Bacteriology of wounds

Time of examination Test compound (h) Pig 2 Pig 3 OpSite 48 HMG HMG 96 HMG HMG Sugar paste 48 HMG 96 HMG Irgasan diluent 48 - HMG 96 HMG Irgasan 48 S. faecalis, coliforms S. faecalis, coliforms 96 S. faecalis, coliforms S. faecalis, coliforms Chlorhexidine 48 No growth NA 96 S.faecalis, Ki. edwardsii NA Povidone iodine 48 NA HMG 96 HMG HMG EUSOL (half strength) 48 HMG HMG 96 NA HMG

HMG, Heavy mixed growth (S. epidermidis, S. faecalis, E, coli, non-lactose fermenting coliforms), NA No aspirate. - Treatment not tested. with connective tissue to the level of sur- numbers ofGram-positive cocci were present rounding skin, while those in the first pig in the surface exudate above the leucocytic infilled similarly to the controls. Epidermal layer, except in one wound where they were regeneration was well advanced, migrating also present in the apocrine glands. The across infilling tissue on the same plane as combination of packing wounds with sugar the uninvolved epidermis. However, the paste and covering with OpSite gave a maturity of the deeper connective tissue was healthy ingrowth of granulation tissue com- more varied than the controls. Large parable to the effect of using OpSite alone; no Effect of dressings on moist wound healing I67 Table 3. Antibacterial activity of wound exudates blasts. Epidermal migration was inhibited in at 48 h against S. epidermidis three of four wounds treated with Irgasan and in one of two wounds treated with the Test compound Zone diameters (mm) diluent. Moderate numbers of Gram-positive cocci were seen on the surface of wounds, OpSite 7.5, 13 higher numbers being present with the Sugar paste IO-I2 diluent. Staphylococci were not present in Irgasan diluent 7.5 wounds treated with Irgasan. Irgasan 2I-25 Irgasan Chlorhexidine i6-I7 appeared no more toxic than its base solu- Povidine iodine 7.5 tion, but that itself delayed wound healing. EUSOL (halfstrength) 7.5 Chlorhexidine gluconate * Diameter of test well, 7.5 mm. The four wounds which were treated with 0.2% chlorhexidine gluconate exhibited Table 4. ph of wound exudates delayed healing in this model. All wounds showed a 75% reduction of infilling with No. of Mean pH new connective tissue; ingrowth consisted of Test compound samples (range) immature repair tissue with little organiza- tion offibroblasts and few OpSite IO 7.5 (7.3-8.2) regenerating blood Sugar paste 8 5.5 (4.3-6.7) vessels. However, 0.2% chlorhexidine gluco- Irgasan diluent 2 7. I (6.5-7.8) nate was the only treatment to eradicate all Irgasan 4 7.2 (7.1-7.6) bacteria at 48 h. Chlorhexidine 4 7.6 (7.4-8.o) Povidone iodine 4 7.0 (6*9-7-1) EUSOL (half strength) 3 7.6 (7.3-8.i) Povidone iodine Four wounds were treated with o.8% (8 mg/ ml) povidine iodine, of which two had a 33% deficiency of infilling with connective tissue deleterious or toxic effects were observed. and two were almost completely infilled. The Better antimicrobial activity of sugar paste former contained less mature tissue and occurs with more frequent application, e.g. many cotton fibres. Large numbers of bac- every 12 h, than was observed in this model teria were seen and cultured in the exudate when wounds were packed at 48 and 72 h. from all four wounds. It appears that the antibacterial action of povidine iodine was Irgasan and its base neutralized by protein binding at the concen- tration used but there was sufficient activity Four wounds were treated with 0.2% Irga- remaining to delay wound healing in two of san and two with its base solution. There was four wounds. some inhibition of healing by the base solu- tion with a 25-50% deficiency of infilling EUSOL half-strength with new connective tissue. Cotton fibres were trapped within immature repair tissue Four wounds were treated with half strength and gave rise to a 'foreign body' reaction. EUSOL, of which three were infilled com- Three out of four wounds treated with pletely and one had a 33% deficiency. In the Irgasan had a 5o% deficiency ofinfilling with former, the connective tissue was dense and connective tissue, but one filled in com- organized with many functioning new blood pletely. Irgasan did not inhibit endothelial vessels. In the latter, there were many cell proliferation nor orientation of fibro- trapped cotton fibres and a cellular reaction. I68 H.G. Archer et al. Epidermal migration had occurred in all four This controlled study was set up to com- wounds. Gram-positive cocci were seen in pare packing ofwounds with sugar paste and large numbers in three out of four wounds with various antiseptics held in position on but had not penetrated the granulation gauze. In each case, bundles of gauze fibres tissue. were incorporated into new connective tis- sue and caused a 'foreign body' reaction. Discussion This delayed and disrupted the natural heal- The use of Stomahesive rings to enclose ing process as studied under OpSite film. If wound treatments and prevent cross-over the gauze had been changed, as in clinical was satisfactory. The rings were easy to use practice, most of the new connective tissue and stayed firmly adherent to the skin for 7 would have been removed with it. Such days despite new hair growth; they provided adhesion has been studied in a controlled adequate wound protection. Their use in model of partial thickness wounds in the pig conjunction with OpSite gave a 'wound (Varley & Barnett I986). No such adhesive chamber' enabling the collection of exudate effect occurred with wounds packed with and easy observation. Unfortunately, the sugar paste, which can be directly compared rings may have produced an artefact because within this model, and new connective tissue the adhesive became softened by body heat was laid down without disruption and delay. and a small amount of gum leaked into all A similar quantity of connective tissue was wounds. The principal component of the produced within the experimental sugar adhesive is karaya gum, which has been wound as when it was covered with OpSite separately studied for wound healing proper- film alone. All antiseptic treatments showed ties (Lowthian & Barnett I985). This effect some delay of healing. was, however, common to all wounds and Chlorhexidine caused the greatest delay of did not seem to alter reproducibility of wound healing in this model, and had results. All wounds other than those treated similar effects in a study using guinea-pigs with chlorhexidine gluconate were colonized exposed to 0.5% chlorhexidine gluconate with bacteria, mostly Escherichia coli, Strepto- solution (Niedner & Schopf I 986). Irrigation coccus faecalis and S. epidermidis. of gingival wounds in rats with 0.5% chlor- It was appreciated that the use of different hexidine retarded healing whereas o. I% and medicaments on one animal could lead to 0.2% were comparable with saline (Kallen- practical difficulties in this trial. The design of berger 1979). In a model of corneal abrasion the experiment was to minimize these prob- in rabbits, irrigation with concentrations of lems given that there were insufficient funds 2.0 and 4.0% chlorhexidine significantly to increase the number of pigs used. All slowed the healing rate (re-epithelialization) histological assessments were made 'blind', but concentrations of i.o% did not (Bowes the treatments being coded throughout the Hamill et al. I984). The manufacturer's experiment. The results indicated that the recommended concentration for wound irri- design was satisfactory since a difference gation with chlorhexidine gluconate is between treatments has been shown and the 0.05%; this level was shown not to delay results obtained for OpSite controls and wound healing in rats in conditions when sugar paste from different animals were i.o% chloramine significantly delayed colla- similar. With only four replicate wounds gen production (Brennan et al. I986). Simi- available for each antiseptic treatment, and larly, in an artificially infected wound model the use of one concentration which could in guinea-pigs, 0.05% chlorhexidine gluco- only be applied on a 48-h dressing change nate irrigation totally prevented sepsis and basis, the limitations of the experiment must did not delay wound healing (Platt & Buck- be considered together with our quantitative nall I984). assessment on healing at 7 days. In this study we noted impairment of Effect of dressings on moist wound healing I69 wound healing by a solution containing 8 lialization in wounds treated with a pH 3.5 mg/ml povidone iodine. Connolly and Gil- solution compared with wounds treated with more (1979) reported that 75 jug/ml povi- neutral and alkaline solutions. Leveen et al. done iodine fully inhibited (and io jug/ml (I973) also demonstrated increased rates of partially) the chemotactic movement ofpoly- healing at acid pH values. Our observations morphonuclear leucocytes, essential in the of low pH values in sugar paste treated early stages of wound healing. It may be wounds are intriguing but without further expected that io% (ioo mg/ml) povidone studies are of unknown significance. iodine, the strength recommended for use in This type of controlled study of moist clinical practice, would have a serious dele- wound healing, using the pig as opposed to terious effect if applied frequently. other animal species where the dermis is Brennan and Leaper (I985) perfused the different (Gangjee et al. I985), is thought rabbit ear chamber with full-strength EUSOL suitable for studying other products to ascer- and noted a stagnation of blood flow in fine tain whether they are equivalent, better or capillaries within seconds. Cessation ofblood worse than OpSite film alone, which can be flow followed within minutes and they noted considered as the standard control treat- a subsequent delay in the repair process. A ment. pilot animal study (unpublished data) has The findings of this study clearly demon- been performed in which ribbon gauze strate that our sugar paste does not impair soaked in half-strength EUSOL and paraffin the wound healing process as shown by was packed into full thickness wounds in the chlorhexidine gluconate 0.2% and Irgasan pig and covered with Gamgee and Micropore 0.2%. There is currently a move away from tape; after 5 days, examination by histology the regular treatment of wounds with anti- showed little infilling of the wound cavity by septics and our data supports the notion that connective repair tissue. The results of the such treatments can be harmful and possibly present study, which showed minimal counter productive. Sugar paste has now delayed healing with half-strength EUSOL, been used on many patients with infected may have been different had more frequent and malodorous wounds (Middleton & Seal packing been possible which would have I985, I989) with excellent results and the maintained higher levels of free chlorine. data presented here indicates that sugar We have found that wounds healed satis- paste may be the treatment of choice for factorily without the need for sterility. Col- wounds that are traditionally treated with onization of their surface with bacteria did antiseptics. not impair the formation of collagen tissue nor epidermal migration. The situation in an infected wound or abscess cavity, where pus Acknowledgements is present, is different, or when there is We are very grateful for advice and assis- cellulitis around the wound. In these circum- tance from Professor J.T. Scales, OBE, Honor- stances, wound healing can be delayed by ary Director, Department of Research in the infective process and it may be more Plastic Surgery, Mount Vernon Hospital, to important to inhibit bacterial growth even if Gary Batchelor and Nicolas Jones for caring collagen formation is delayed. for the animals and administering the anaes- There is a growing body of evidence to thetic, and to Mrs Angela Matthews for suggest that a low pH on the surface of a typing the manuscript. wound will encourage the healing process. In a double blind study, Kaufman et al. (I985) applied buffered solutions to experi- References mental second-degree burns in guinea-pigs ALPER J.C. (I986) Recent advances in moist and noted significantly increased re-epithe- wound healing. South. Med. J. 79, I398-I404. I 70 H.G. Archer et al. ALVAREZ O.M., MERTZ P.M. & EAGLSTEIN W.H. LAUFER M., ASHKENAZI C., KATZ D. & WOLMAN M. 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