THE PIG AS A MODEL FOR HUMAN WOUND HEALING

Perspective article

The pig as a model for human wound healing

TORY P. SULLIVAN, MD; WILLIAM H. EAGLSTEIN, MD; STEPHEN C. DAVIS, BS; PATRICIA MERTZ, BA

The medical literature describes numerous in vitro and in vivo wound-healing models. The selection of an animalmodel depends on a number of factors including availability, cost, ease of handling, investigator familiarity, andanatomical/functional similarity to humans. Small mammals are frequently used for wound healing studies, however,these mammals differ from humans in a number of anatomical and physiological ways. Anatomically and physiologi-cally, pig skin is more similar to human skin. The many similarities between man and pig would lead one to believethat the pig should make an excellent animal model for human wound healing. The purpose of this paper is to reviewthe existing literature for evidence of this supposition and determine how well the various models correlate to humanwound healing. Studies of wound dressings, topical antimicrobials, and growth factors are examined. Over 180 articleswere utilized for this comparative review. Our conclusion is that the porcine model is an excellent tool for the evaluationof therapeutic agents destined for use in human wounds. (WOUND REP REG 2001;9:66–76)

The medical literature describes numerous in vitro and bFGF Basic fibroblast growth factorin vivo wound-healing models. Many models are designed EGF Epidermal growth factorto isolate specific events and mechanisms, however, each IL-1� Interleukin-1�

model is ultimately judged by its ability to predict howa treatment will behave in a human wound (under clinicalconditions). Obviously, human studies are the most accu-rate way of determining the effectiveness of wound- larity to humans. Small mammals, such as the rabbit,treatment agents and dressings. However, human studies guinea pig, rat and mouse, are frequently used in woundare often impractical, in that it is difficult to identify healing studies as they are inexpensive and easy to han-sufficient numbers of patients with identical or similar dle. Despite these advantages, small mammals differwounds for randomized trials. Furthermore, objective from humans in a number of anatomical and physiologi-measurements of human wound healing are limited as cal ways. For example, these mammals have a denseaccurate histological assessment of healing wounds re- layer of body hair, thin epidermis and dermis and, morequires frequent biopsies during the healing process. Ethi- significantly, they heal primarily through wound contrac-cal considerations may also prevent the use of untreated tion as opposed to reepithelialization.or vehicle-treated control wounds, limiting the quality of Anatomically and physiologically, pig skin is morethe data from human studies. For these and other rea- similar to human skin. Both pig and man have a thicksons, animal studies are often used to model human epidermis. Human epidermis ranges from 50 to 120 �mwound healing and the efficacy of current and potential and the pig’s from 30 to 140 �m, but because in both ani-therapies. mals the epidermal thickness varies considerably based

Selection of an animal model depends on a number on body site, a better measure is the dermal-epidermalof factors including availability, cost, ease of handling, thickness ratio.1 It has been reported that this ratioinvestigator familiarity, and anatomical/functional simi- ranges from 10 : 1 to 13 : 1 in the pig and is similar to

comparable measurements of human skin.2 Both manand pig show well-developed rete-ridges and dermal pap-

From the University of Miami School of Medicine, Depart- illary bodies, and abundant subdermal adipose tissue.3–5

ment of Dermatology, Miami, Florida.Porcine dermal collagen is similar to human dermal colla-Reprint requests: Patricia Mertz, 1600 NW 10th Ave,gen biochemically, accounting for its use in a number#2079A, P.O. Box 016250 (R-250), Miami, FL 33101.

Fax: (305) 243-4422. of wound healing products.6 Although pig dermis has66

WOUND REPAIR AND REGENERATIONVOL. 9, NO. 2 SULLIVAN ET AL 67

a relatively high elastic content as compared to other lead one to believe that the pig should make an excellentanimal model for human wound healing. The purpose ofmammals, it is less than that found in human skin.7 Nei-

ther pig nor man has a panniculus carnosus as is found this paper is to examine the existing literature for evi-dence of this by determining how well the pig modelin small (loose) skinned animals.5 The size, orientation,

and distribution of blood vessels in the dermis of the pig correlates to human wound healing. This relationship isdiscussed in the context of other current models whereare similar to blood vessels in human skin; however, the

subepidermal plexus, which supplies adenexal struc- applicable.Over 180 articles were obtained by searching Med-tures, is somewhat less developed in the pig8–10 The num-

ber and distribution of adenexal structures in swine and line� and by hand searching several wound care journalsnot indexed in Medline� for this comparative review.man are similar but not identical.1,11,12 Both pig and man

have sparse body hair which, unlike many animals, prog- Medline� searches were carried out by cross referencingspecific treatments (e.g., topical iodine, hydrocolloidresses through the hair cycle independently of neigh-

boring follicles.5 This is important as adenexal structures, dressings, epidermal growth factor) with the various ani-mal models (e.g., rat, mouse, pig) and/or the major sub-including hair follicles, play an important role in reepithe-

lialization. Adenexal differences between pig and man ject headings (MeSH) wound healing and skin to obtainarticles of interest. Ideally, only prospective, randomized,are that pig skin contains no eccrine glands, and unlike

man, apocrine glands are distributed through the skin controlled studies with well-defined, objective outcomemeasurements would be included in this review. How-surface.1 Functionally, pig and man are similar in terms

of epidermal turnover time, type of keratinous proteins, ever, the current state of the literature does not makesuch a review possible. A small minority of the 180 plusand lipid composition of the stratum corneum.12–14 Immu-

nohistochemical staining of porcine and human skin articles referenced in this paper includes case series andother reports that contain data that is not strictly con-shows similar staining patterns for a number of antigens

including keratins 16 and 10, filaggrin, collagen IV, fibro- trolled or randomized.nectin, and vimentin.15 Figure 1 visually illustrates thehistological similarities between pig and human skin. Dressings

Occlusive dressings have been extensively studied inMan and pig heal through physiologically similar pro-cesses.16 Most small animals have a panniculus carnosus both pig and man. Winter’s classic experiments showing

the benefits of a moist wound environment for optimaland rely on wound contraction for wound closure. Con-versely, man and swine close partial-thickness wounds healing were first performed in a porcine model with

subsequent confirmation in studies of human patients.19,20largely though reepithelialization. Additionally, the pig’soverall physiology is close to human physiology, with Since these early experiments, the effects of dressings on

wounds has generally been identical in the two animals.most key organ systems being similar in anatomy andfunction.17,18 (Table 1) For example, partial-thickness wounds in the

pig show accelerated reepithelialization when treatedThe many similarities between man and pig would

FIGURE 1.Comparison of histological fea-tures from swine and human skin. H&Estained section taken through compara-ble portions of the dermis in both tissues.

WOUND REPAIR AND REGENERATIONMARCH–APRIL 200168 SULLIVAN ET AL

Table 1. Effect of various wound dressings on healing in the healing of full-thickness wounds in both man andhuman and swine studies

pig.42–44

Treatment References Human Pig Studies of wound healing in the pig have progressedCalcium Alginate 30, 91–96 ↑ ↑ beyond questions of efficacy and allowed the investiga-Hydrocolloid-Acute Partial 21–31, 97 ↑ ↑ tion of possible mechanisms by which dressings alterThickness

wound healing. Porcine studies have been used to answerHydrocolloid-2nd Degree Burn 24, 82, 98–102 ↑ ↔questions including the impact of occlusion on bacterialHydrogel-Acute Wound 42, 103–105 ↑ ↑

Film Dressing-Acute Wound 21, 24, 32–44 ↑ ↑ proliferation and extent of foreign body reactions toFilm Dressing-2nd Degree Burn 98, 106 ↔ ↔

dressing components using experimental methods notFoam Dressing-Acute Partial 107, 108 ↑ ↔

ethically feasible in human patients.45,46 For example, pigThicknesswounds have been inoculated with pathogenic bacteria↑ Increased Healing Rate ↓ Decreased Healing Rate ↔ No Change in

Healing Rate and entire wounds biopsied to better understand theShading indicates concordance of results between human and pig studies.

wound healing process. Thus, in addition to correlatingwell with results in human studies, the porcine modelallows for an in-depth examination of the wound healing

with a hydrocolloid dressing.21 Similarly, in man numer- process not otherwise possible.ous studies have shown hydrocolloid dressings to besuperior to nonocclusive treatments such as plain gauze Topical antimicrobials/antibiotics

An examination of the literature clearly shows the bene-and other therapies in the treatment of split skin graftdonor sites and partial-thickness wounds.22–31 fits of the porcine model for the study of topical antimi-

crobial agents over other models, especially in vitroStudies of semipermeable polyurethane dressingshave also shown an excellent degree of concordance models. When studied in vitro antimicrobials/antibiotics

almost universally show toxicity. (Table 2) This is unsur-between human and pig studies. In well-controlled pigstudies, polyurethane dressings have been shown to im- prising considering the delicate nature of many in vitro

model systems and the nonspecific mechanisms of actionprove the rate of reepithelialization in acute partial-thickness wounds.21,32 The proliferative response of por- of some antimicrobials.

In vitro povidone-iodine is highly cytotoxic to kera-cine keratinocytes in acute partial-thickness wounds in-creased 21% with film occlusion.33 Identical results have tinocytes and fibroblasts even at low concentrations.47,48

Of eight antimicrobials tested by Cooper et al.,48been found in human studies. In one study comparingtwo different film dressings to fine mesh gauze in 60 povidone-iodine was the most toxic to fibroblasts in cul-

ture. However, povidone-iodine shows little toxicity inconsecutive skin graft donor sites, reepithelializationwas noted to be significantly more rapid in film-treated porcine or human wound healing trials. Geronemus et al.

failed to see any significant effect on the healing partial-wounds.34 In a double blind study of five patients compar-ing the efficacy of common adhesive bandages (nonoc- thickness wounds in swine when treated with a povi-

done-iodine ointment.49 Results in man correlate wellclusive dressing) to a polyurethane dressing for thetreatment of experimentally induced suction blister with porcine studies. In studies of partial-thickness

wounds in man performed by Gruber et al., wounds werewounds, the polyurethane dressing–treated wounds hada superior rate of reepithelialization.35 At least 7 addi- treated with 10% povidone-iodine every 6 hours until

complete healing.50 Povidone-iodine–treated woundstional studies confirm these results.24,36–41 Occlusivedressings, including films, have also been shown to speed healed significantly more rapidly than control wounds

Table 2. Result of topical application of antimicrobial agents on wounds in various species of animals and in vitro

Treatment References Human Pig Other Animal In Vitro

Bacitracin 42, 43, 109–111 ↔ ↑ ↔ ↓Benzoyl Peroxide 105, 112–116 ↑ ↑ ↓ N/DPovidone-Iodine 42–45, 111, 117–123 ↔ ↔ ↔ ↓Nitrofurazone 42, 46, 112, 113, 124–126 ↑ ↓ N/D ↓Mupirocin 46, 105, 127–133 ↔ ↔ N/D ↓Scarlet Red 31, 86, 91, 105, 134–141 ↑ ↑ N/D N/DTriple Antibiotic Ointment 41–48, 111 ↑ ↑ ↓ ↓

↑ Increased Healing Rate ↓ Decreased Healing Rate ↔ No Change in Healing Rate N/D No Data

Shading indicates concordance of results between human and pig studies.


exposed to air (9.3 days vs. 12.4 days) and did not heal at results using EGF in partial-thickness wounds in pigs.55–57

Additionally, full-thickness wounds in the pig treateda rate significantly different from saline-treated wounds.These results indicate that povidone-iodine did not nega- with EGF have shown trends toward improved healing.58

Studies in humans have paralleled these results. In atively affect wound healing, the predicted result basedon in vitro results. prospective, randomized, double blind trial of EGF for

the treatment of skin graft donor sites in 12 patients,Similarly, in vitro testing has generally shown thecomponents of triple antibiotic ointment (bacitracin zinc, Brown’s group demonstrated significantly accelerated re-

epithelialization as compared to vehicle-treated con-neomycin, and polymyxin B sulfate) to be cytotoxic inconcentrations found in wounds.41,42,51 Porcine and trols.59 Another well-controlled human trial showed

benefit from EGF treatment in both partial-thicknesshuman studies contrast sharply with these in vitro re-sults. Geronemus et al. demonstrated that triple antibi- burns and skin graft donor sites.60 Although the prepon-

derance of evidence shows that EGF speeds the reepithe-otic ointment significantly increased the rate ofreepithelialization of partial-thickness wounds in the pig lialization of human wounds, it should be noted that

Cohen et al. did not find this result in their work.61 In aover both untreated and vehicle-treated controls.49 Simi-larly, three authors have shown benefit in man from the placebo-controlled double blind study they found that

EGF, when used to treat partial-thickness wounds in nor-treatment of partial-thickness wounds with triple antibi-otic ointment.41,52,53 This same agreement of results be- mal volunteers, did not significantly increase the rate of

wound reepithelialization.61 The cause of these discor-tween human and porcine trials has been seen in studiesof benzoyl peroxide, mupirocin, and scarlet red. dant results may be a small study size or the subjective

nature of the evaluation of human wounds. The authors’These studies show a weakness of in vitro testingand a corresponding strength of the porcine model. Cell hypothesis that their divergent results arise from their

use of patients without concurrent disease (patients withcultures are relatively delicate systems with little homeo-static regulatory ability. Cells in culture are easily dis- severe burn injuries were included in the other studies)

is an excellent one. Pigs used in wound healing studiesturbed by minor changes in growing conditions, whereascells in the wound environment are more robust. In vivo receive numerous wounds, are handled frequently, and

undergo general anesthesia multiple times, placing greatthe organism’s homeostatic mechanisms create a com-plex self-regulating milieu where cells are able to effec- physiological stress on the animal. As such the pig model

may most closely approximate wounds in patients withtively compensate for changes in the wound environmentas induced by the addition of antimicrobials and antibiot- severe illness. Another possible reason for the discrep-

ancy may be the use of a vehicle with potent wound-ics. Porcine wound healing much more closely modelswhat occurs in a human wound. healing effects. Although the authors in this study used

a vehicle control, if the vehicle’s effects on the rate ofGrowth factors wound healing are great (i.e., it rapidly promotes heal-

ing), it can obscure the effects of an active but weakThe isolation of various growth factors and the develop-ment of recombinant technology over the past several promoter of wound healing. We have seen this effect

frequently in our own studies of wound healing in thedecades has resulted in the testing of many of thesefactors in animals and humans. Within this group of pig.

Studies of interleukin-1� (IL-1�) and basic fibroblastagents there is excellent agreement between human andpig studies. (Table 3) growth factor (bFGF), indicate superiority of the pig as

a model for human wound healing as compared to otherEpidermal growth factor (EGF) has been extensivelystudied in the pig. In one study, varying concentrations animal models. Preliminary evidence suggests that IL-1�

may impair wound strength in rats.62 However, in studiesof EGF significantly accelerated partial-thickness woundhealing.54 At least three other authors have shown similar of both partial-thickness and full-thickness wounds in

Table 3. Effect of growth factor applied to human and animal wounds and in vitro


Epidermal Growth Factor 49–56, 142–145 ↑ ↑ ↑ ↑Interleukin-1� 57–61, 146–150 ↑ ↑ ↓ ↑Basic Fibroblastic Growth Factor 49, 62–69, 151–156 ↔ ↔ ↑ ↑Platelet-Derived Growth Factor 62, 63, 157–168 ↑ ↑ ↑ ↑

↑ Increased Healing Rate ↓ Decreased Healing Rate ↔ No Change in Healing Rate



the pig, IL-1� significantly enhanced healing as compared reliable model for predicting human wound healing re-sults.to both air-exposed and vehicle-treated wounds.63,64 Like-

wise in man, Barbul has reported that IL-1� effectivelyaccelerates the rate of reepithelialization of split-thick- Vehicles and miscellaneous treatments

A variety of substances and techniques have been evalu-ness skin graft donor sites.65 IL-1� appears to improvewound healing in both pig and man primarily through ated in both man and pig as shown in Table 4. Clinicians

have long recognized that oral corticosteroids impairits actions on keratinocytes.66 Since reepithelialization isproportionally more important to wound healing in pig wound healing and increase the risk of wound complica-

tions.75,76 The effect of topical steroids on wound healingand man than to wound healing in the loose-skinnedmammals, this may explain IL-1�’s possible lack of effi- was thought to be similar to the effects of oral steroids,

but it was not empirically proven until Winters demon-cacy in rats despite beneficial effects in porcine andhuman wounds. strated that pretreatment of the skin with topical cortico-

steroids impaired the subsequent reepithelialization ofConversely, bFGF’s primary action is on the fibro-blast, accounting for its superior results when used in partial-thickness wounds in the pig.77 Two other well-

controlled studies of partial-thickness wounds in the pigwound healing trials in loose-skinned animals comparedto similar trials in pig and man. bFGF increases the rate have shown that the topical application of some classes

of corticosteroids after injury can cause significant delayof wound healing and reepithelialization in both ulcersand excisional wounds in the rabbit.67,68 In the guinea in wound reepithelialization. Eaglstein and Mertz found

that the fluorinated steroid triamcinolone acetonide sig-pig, bFGF enhances both reepithelialization and tensilestrength of full-thickness wounds.69,70 Full-thickness nificantly delayed reepithelialization.78 Similar effects

from topical steroids have been observed in man. Reepi-wounds in diabetic mice heal significantly faster as mea-sured by granulation tissue thickness and wound closure thelialization of experimentally induced suction blister

wounds is significantly delayed by topical dexametha-after treatment with bFGF.71,72 Three studies have evalu-ated the use of bFGF in the porcine partial-thickness sone.79 In studies of suction blister wounds and tape-

stripped skin, topical steroids have been shown towound model. In two of the studies bFGF did not signifi-cantly improve the rate of reepithelialization.49,73 Like- decrease DNA synthesis and the normal proliferative re-

sponse of the human epidermis in response to injury.80,81wise, in a small, randomized, double-blind study of 11human patients, bFGF had no effect on reepithelializa- Porcine studies have also been important for empiri-

cally evaluating debridement, a technique commonly em-tion of split skin graft donor sites as compared to vehicle-treated control wounds.74 The disparity between the ployed in burn patients. Elad et al. and Davis et al. found

that early debridement of partial-thickness burn woundshuman and porcine studies and the small-mammal stud-ies may reflect the fact that bFGF exerts its primary in the pig leads to improved reepithelialization.82,83 Inter-

estingly, Davis found that early debridement (< 24 hours)actions on dermal components of the skin which play agreater role in wound healing in small, loose-skinned was required to see benefit. A study of partial-thickness

burns in children parallels the results in the pig andanimals. Since pigs heal in a manner that is physiologi-cally comparable to humans, the use of a porcine model supports the use of debridement for the management of

partial-thickness burns. Similarly, nii-Amon-Kotei et al.allows for a more subtle evaluation of growth factors inwound healing. Because of the anatomical and physiolog- used dermabrasion to debride partial-thickness burn

wounds and found more rapid reepithelialization.84ical similarity between man and pig, the pig is a more

Table 4. Effect of vehicle and miscellaneous treatment of wounds in humans, animals, and in vitro


Corticosteroids 70–76, 170–176 ↓ ↓ ↓ ↓Anabolic Steroids 74, 167, 177–180 ↑ ↑ ↑ ↑Petrolatum 30, 42, 43, 104, 111, 181 ↔ ↔ N/D ↔Aloe Vera-Full Thickness Wounds 105, 182–185 ↓ ↔ ↑ N/D

Burn Debridement 97, 98, 186–191 ↑ ↑ ↓ N/DTretinoin 82–87, 105 ↑ ↑ N/D N/DRGD Peptide 192–196 ↑ ↑ ↑ ↑

↑ Increased Healing Rate ↓ Decreased Healing Rate ↔ No Change in Healing Rate N/D No Data



The pig model has been an effective tool for thestudy of other topical medications, including trans-retinoic acid (tretinoin). Using a porcine model of partial-thickness wounds, Mertz et al. demonstrated a 55% and18% increase in the relative rate of reepithelialization inwounds pretreated with all trans-retinoic acid as com-pared to air-exposed and vehicle controls, respectively.85

Hung et al. also demonstrated that pretreatment with0.05% tretinoin cream significantly increased the rate ofreepithelialization in partial-thickness wounds in pigs.86

Results in man have paralleled those of the porcinemodel. In one study of 123 patients undergoing dermabra-sion, Mandy noted more rapid clinical reepithelializationin the 88 patients who were pretreated with daily 0.05%tretinoin cream.87 A double-blind placebo-controlledstudy of 16 patients pretreated with 0.1% tretinoin cream FIGURE 2. Concordance between results of wound healing stud-for two weeks prior to a 35% trichloroacetic acid peel ies performed in humans and swine, small mammals or in vitro.found significantly more rapid reepithelialization of theface, hands, and forearms of pretreated patients.88 Five

review contains a significant subjective component. Cer-patents undergoing electro-epilation had healing timestain treatments show dissimilar results between thesignificantly reduced by pretreatment with tretinoin inporcine and human studies, such as the treatment ofcomparison to untreated control areas on the same pa-partial-thickness burns with hydrocolloid and hydrogeltients.89 Furthermore, 16 weeks of pretreatment with tret-dressings. It is impossible to say whether these dissimilarinoin cream in actinically damaged skin speededresults represent true differences between burn woundsreepithelialization of full-thickness wounds in a study ofin humans and pigs or just differing study designs. Sincefour elderly men. Pretreated wounds were up to 50%the quality of research in the pig model is generally supe-smaller on days 6, 8 ,and 11 postwounding as comparedrior to similar studies in humans, it is interesting to hy-to untreated controls.90

pothesize that further, more rigorous evaluations inhuman patients might lead to even more concordant re-sults.DISCUSSION

Because no model will ever completely replicate clin-A total of 25 wound therapies have been evaluated inical human wound healing, it is essential that the modelthis paper. Where the various models can be comparedutilized be selected with care. For example, studies ofto human studies the porcine model is in agreement withthe effects of vitamin C deficiency on wound healinghuman studies 78% of the time vs. 53% and 57% for theare generally performed in the guinea pig because, likesmall-mammal and in vitro studies, respectively (Figurehuman beings, guinea pigs require vitamin C from dietary2). Clearly it is difficult to reliably compare studies suchsources. Most other animals, including the pig, are able toas these which vary enormously in quality and studysynthesis their own vitamin C and thus do not make gooddesign. Variables that complicate the comparisons in-models for the effects of dietary vitamin C deficiency. Thisclude methods of wounding, wound assessment tech-example clearly illustrates the importance of carefulniques, treatment schedules, and lack of universalmodel selection. Clearly, human studies of wound healingcontrols (i.e., air-exposed controls) among the variousagents will always be the gold standard. However, thestudies. Povidone-iodine is illustrative of the complexitybody of research presents a clear result: the porcine modelof the comparison. It is available in over 23 productis an excellent tool for the evaluationof therapeutic agentsformulations, more than any other antiseptic. Multiplydestined for used in human wounds.this by the numerous concentrations of iodine and the

difficulty of the comparison becomes evident. These nu-merous variables make a rigorous comparison impossi- REFERENCESble; however, every attempt has been made to compare

1. Meyer W, Scharz R, Neurand K. The skin of domestic mammalssimilar studies and to place more weight on the results as a model for the human skin with special reference to the

domestic pig. Curr Probl Dermatol 1978;7:39–52.of controlled, blinded trials. Nevertheless, ultimately this


2. Vardaxis NJ, Brans TA, Boon ME, Kreis RW, Marres LM. Confocal 27. Nemeth AJ, Eaglstein WH, Taylor JR, Peerson LJ, Falanga V. Fasterhealing and less pain in skin biopsy sites treated with an occlusivelaser scanning microscopy of porcine skin; implications for human

wound healing studies. J Anat 1997;190:601–11. dressing. Arch Dermatol 1991;127:1679–83.28. Blitz H, Keissling M, Kreysel HW. Comparison of hydrocolloid3. Morris GM, Hopewell JW. Epidermal cell kinetics of the pig: a

review. Cell Tissue Kinetics 1990;23:271–82. dressing and saline gauze in the treatment of split skin graft donorsites. An environment for healing: the role of occlusion. In: Ryan4. Montagna W, Yun JS. The skin of the domestic pig. J Invest Derma-TJ, editor. Royal Society of Medicine International Congress andtol 1964;43:11–21.Symposium Series, No 88; London, Royal Society of Medicine,5. Winter GD. A study of wound healing in the domestic pig. PhD1985: 125.Thesis, Birbeck College, University of London, 1966.

29. Cadier MA, Clarke JA. Dermasorb versus jelonet in patients with6. Heinrich W, Lange PM, Stirz T, Iancu C, Heidermann E. Isolationburns skin graft donor sites. J Burn Care Rehabil 1996;17:246–51.and characterization of the large cyanogen bromide peptides from

30. Porter JM. A comparative investigation of re-epithelialization ofthe �1- and �2-chains in pig skin collagen. FEBS Letters 1971;16:split skin graft donor areas after the application of hydrocolloid63–7.and alginate dressings. Br J Plast Surg 1991;44:333–7.7. Marcarian HQ, Calhoun ML. Microscopic anatomy of the integu-

31. Tan ST, Roberts RH, Blake GB. Comparing DuoDerm E with scarletment of adult swine. Am J Vet Res 1966;27:765–72.red in the treatment of split skin graft donor sites. Br J Past Surg8. Forbes PD. Vascular supply of the skin and hair in swine. In:1993;46:79–81.Montagna W, Dobson RL. editors. Advances in the biology of skin:

Hair growth. Vol. 9. Oxford: Pergamon, 1969: 419–32. 32. Eaglstein WH, Davis SC, Mehle AL, Mertz PM. Optimal use of anocclusive dressing to enhance healing. Arch Dermatol 1988;124:9. Bloch BF, Pinkus H, Spalteholtz W, editors. Anatomie der Haut.392–5.Berlin: Springer Verlag, 1927:32–47.

33. Levine R, Agren MS, Mertz PM. Effect of occlusion on cell prolifer-10. Mortite AR, Henriques FC. Studies of thermal injury II. The relativeation during epidermal healing. J Cut Surg Med 1998;2:193–8.importance of time and surface temperature in the causation of

cutaneous burns. Am J Path 1947;23:695–720. 34. Barnett A, Berkowitz RL, Mills R, Vistnes LM. Comparison ofsynthetic adhesive moisture vapor permeable and fine mesh gauze11. Gray GM, Yardely HJ. Lipid compositions of cell isolated from

pig, human, and rat epidermis. J Lipid Res 1975;16:434–40. dressings for split-thickness skin graft donor sites. Am J Surg1983;145:379–81.12. Weinstein GD. Comparison of turnover time and of keratinous

protein fractions in swine and human epidermis. In: Bustad LK, 35. Woodley DT, Kim YH. A double-blind comparison of adhesiveMcClellan RD, editors. Swine in biomedical research. Seattle: bandages with the use of uniform suction blister wounds. ArchFrayn, 1966:287–9. Dermatol 1992;128:1354–7.

13. Nicolaides N, Fu HC, Rice GR. The skin surface lipids of man 36. Lobe TE, Anderson GF, King DR, Boles ET Jr. An improved methodcompared with those of eighteen species of animals. J Invest of wound management for pediatric patients. J Pediatr Surg 1980;Derm 1968;51:83–9. 15:886–9.

14. Gray GM, White RJ, Williams RH, Yardley HJ. Lipid composition 37. Bergman RB. A new treatment of split skin graft donor sites. Archof the superficial stratum corneum of pig epidermis. Br J Dermatol Chir Neerl 1977;29:69–72.1982;106:59–63. 38. Stair TO, Dorta J, Altieri MF, Lippe MS. Polyurethane and silver

15. Wollina U, Berger U, Mahrle G. Immunohistochemistry of porcine sulfadiazine dressings in treatments of partial-thickness burns andskin. Acta histochem 1991;90:87–91. abrasions. Am J Emerg Med 1984:214–7.

16. Hartwell SW. The mechanism of healing in human wounds. Spring- 39. James JH, Watson AC. The use of OpSite a vapour-permeablefield, IL: Charles Thomas, 1955. dressing on skin graft donor sites. Br J Plast Surg 1975;28:107–10.

17. Terris JM. Swine as model in renal physiology and nephrology: an 40. Yadav JK, Singhvi AM, Kumar N, Garg S. Topical phenytoin in theoverview. In: Tumbleson ME, editor. Swine in biomedical research. treatment of split-thickness skin autograft donor sites: a compara-New York:Plenum Press, 1986:1673–89. tive study with polyurethane membrane drape and conventional

dressing. Burns 1993;19:306–10.18. Lee KT. Swine as animal models in cardiovascular research. In:Tumbleson ME, editor. Swine in biomedical research. New York: 41. Leyden JJ, Kligman AM. Wound Healing. In: Leyden JJ, KligmanPlenum Press, 1986:1481–98. AM, editors. Safety and efficacy of topical drugs and cosmetics.

New York: Grune and Stratton, 1982: 275–80.19. Winter GD. Formation of the scab and the rate of epithelializationof superficial wounds in the skin of the young domestic pig. Nature 42. Robins P, Day CL, Lew RA. A Multivariate analysis of factors affect-1962;193:293–4. ing wound healing time. J Dermatol Surg Oncol 1984;10:219–21.

20. Winter GD. Effect of air exposure and occlusion on experimental 43. De Coninck A, Draye JP, Van Strubarq A, Vanpee E, Kaufman L,skin wounds. Nature 1963;200:377–9. Delaey B, Verbeken G, Roseeuw D. Healing of full-thickness

wounds in pigs: effects of occlusive and non-occlusive dressings21. Alvarez OM, Mertz PM, Eaglstein WH. The effect of occlusivedressings on collagen synthesis and re-epithelialization in superfi- associated with a gel vehicle. J Dermatol Sci 1996;13:202–11.cial wounds. J Surg Res 1983;35:142–8. 44. Dyson M, Young S, Pendle CL, Webster DF, Lang SM. Comparison

of the effects of moist and dry conditions on dermal repair. J22. Champsaur A, Amanon R, Nefzi A, Marichy J. Use of DuoDermon skin graft donor sites: comparative study with tulle gras. Ann Invest Dermatol 1988;91:434–9.Chir Plast Esthet 1986;31:273. 45. Marshall DA, Mertz PM, Eaglstein WH. Occlusive dressings. Does

dressing type influence the growth of common bacterial patho-23. Demetriades D, Psaras G. Occlusive versus semi-open dressings inthe management of skin graft donor sites. S Afr J Surg 1992;30:40–1. gens? Arch Surg 1990;125:1136–9.

46. Agren MS, Mertz PM, Franzen L. A comparative study of three24. Madden MR, Nolan E, Finkelstein JL, Yurt RW, Smeland J, Good-win CW, Hefton J, Staiano-Coico L. Comparison of an occlusive occlusive dressings in the treatment of full-thickness wounds in

pigs. J Am Acad Dermatol 1997;36:53–8.and semi occlusive dressing and the effect of the wound exudateupon keratinocyte proliferation. J Trauma 1989;29:924–30. 47. Smoot EC III, Kucan JO, Roth A, Mody N, Debs, N. In vitro toxicity

testing for antibacterials against human keratinocytes. Plast Re-25. Hermans MH. Hydrocolloid dressing versus tulle gauze in thetreatment of abrasions in cyclists. Int J Sports Med 1991;12:581–4. constr Surg 1991;87:917–24.

48. Cooper ML, Laxer JA, Hansbrough JF. The cytotoxic effects of26. Smith DJ, Thomson PD, Bolton LL, Hutchinson JJ. Microbiologyand healing of the occluded skin-graft donor site. Plast Reconstr commonly used topical antimicrobial agents on human fibroblast

and keratinocytes. J Trauma 1991;31:775–84.Surg 1993;91:1094–7.


49. Geronemus RG, Mertz PM, Eaglstein WH. Wound Healing: the 68. Mustoe TA, Pierce GF, Morishma C, Deuel TF. Growth Factorinduced acceleration of tissue repair through direct and inductiveeffects of topical antimicrobial agents. Arch Dermatol 1979;115:

1311–4. analysi of a rabbit dermal ulcer model. J Clin Invest 1991;87:694–703.50. Gruber RP, Vistness L, Pardoe R. The effect of commonly used

69. Slavin J, Hunt JA, Nash JR, Williams DF, Kingsworth AN. Recombi-antiseptics on wound healing. Plast Reconstr Surg 1975;55:472–6.nant basic fibroblast growth factor in red blood cell ghosts acceler-51. Boyce ST, Warden GD, Holder IA. Cytotoxicity testing of topicalates incisional wound healing. Br J Surg 1992;79:918–21.antimicrobial agents to human keratinocytes and fibroblasts

70. Marks MG, Doillon C, Silver FH. Effects of fibroblasts and basicfor cultures skin substitutes. J Burn Care Rehabil 1995;16:97–fibroblast growth factor on the facilitation of dermal wound heal-103.ing by type I collagen matrices. J Biomed Mater Res 1991;25:52. Stahl CM, Grandy RP, Fitzmartin RD, Chelle C, Oshlack B, Gold-683–96.enheim PD. The comparative efficacy and safety of 5% povidone-

71. Okumura M, Okuda T, Nakamura T, Yajima M. Acceleration ofiodine cream for topical antisepsis. Ostomy Wound Managementwound healing in diabetic mice by basic fibroblast growth factor.1990;31:40–9.Biol Pharm Bull 1996;19:530–5.53. Leyden JJ, Bartelt NM. Comparison of topical antibiotic ointments,

72. Tsuboi R, Rifkin DB. Recombinant basic fibroblast growth factora wound protectant, and antiseptic for the treatment of humanstimulates wound healing in healing-impaired db/db mice. J Expblister wounds contaminated with Staphylococcus aureus. J FamMed 1990;172:245–51.Prac 1987;24:601–4.

73. Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound54. Breuing K, Andree C, Helo G, Slama J, Liu PY, Eriksson E. Growthhealing single and synergistic effects on partial thickness porcinefactors in the repair of partial thickness porcine skin wounds.skin wounds. J Clin Invest 1989;84:640–6.Plast Reconstr Surg 1997;100:657–64.

74. Greenhalgh Rieman M. Effect of basic fibroblast growth factor55. Nanney LB. Epidermal and dermal effects of epidermal growthon the healing of partial thickness donor sites. Wound Rep Regfactor during wound repair. J Invest Dermatol 1990;94:624–9.1994;2:113–21.56. Chvapil M, Gaines JA, Gilman T. Lanolin and epidermal growth

75. Wood SH, Lees VC. A prospective investigation of the healing offactor in healing of partial thickness pig wounds. J Burn Caregrafted pretibial wounds with early and late mobilization. Br JRehabil 1988;9:279–84.Plast Surg 1994;47:127–31.57. Mertz PM, Davis SC, Arakawa Y, Cohen A. Pulsed rhEGF treatment

76. Diethelm AG. Surgical management of complications of steroidincreased epithelialization of partial thickness wounds. J Investtherapy. Ann Surg, 1977;185:251–63.Dermatol 1988;90:588. [Abstract]

77. Winters GD. Epidermal regeneration studies in the domestic pig.58. Jijon AJ, Gallup DG, Behzadian MA, Methany WP. AssessmentIn: Maibach DT, Rovee HI, editors. Epidermal Wound Healingof epidermal growth factor in the healing process of clean fullChicago: Year Book Medical Publishers, 1972:71–112.thickness skin wounds. Am J Obstet Gynecol 1989;161:1658–

78. Eaglstein WH, Mertz PM. New Method for assessing epidermal62.wound healing: the effects of triamcinolone acetonide and polyeth-59. Brown GL, Nanney LB, Griffen J, Cramer AB, Yancey JM, Curt-ylene film occlusion. J Invest Derm 1978;71:382–4.singer LJ, Holtzin L, Schultz GS, Jurkiewicz MJ, Lynch JB. En-

79. Jyvasjarvi S, Hopsu-Havu VKA. A model for studies of dermalhancement of wound healing by topical treatment with epidermalsurface epithelialization: with observations on the effects of dexa-growth factor. N Engl J Med 1989;321:76–9.methasone and nandrolone deconate. Arzneim Forsch 1976;3:60. Brown GL, Curtsinger L, Brightwell JR, Ackerman DM, Tobin GR,443–7.Polk HC, George-Nascimento C, Valenzuela P, Schultz G. Enhance-

80. Bauer FW, Boezeman JB, Rijzewijk JJ, Grood RM. Topical cortico-ment of epidermal regeneration by biosynthetic growth factor. Jsteroids delay the proliferative response to sellotape stripping.Exp Med 1986;163:1319–24.Skin Pharmacol 1989;2:204–9.61. Cohen IK, Crossland RN, Garrett A, Diegelmann RF. Topical appli-

81. Devitt H, Clark MA, Marks R, Picton W. A quantitative approachcation of epidermal growth factor onto partial-thickness woundsto epidermal wound healing: the effect of dexamethasone on re-in human volunteers does not enhance re-epithelialization. Plastgenerating epithelium. Br J Dermatol 1978;98:315–23.Reconstr Surg 1995;96:251–4.

82. Eldad A, Simon GA, Kadar T, Kushnir M. Immediate dressing of62. Maish GO, Shumate ML, Ehrlich HP, Vary TC, Cooney RN. Interleu-the burn wound-will it change its natural history. Burns 1991;17:kin-1 receptor antagonist attenuates tumor necrosis factor-233–8.induced alterations in wound breaking strength. J Trauma 1999;

47:533–7. 83. Davis SC, Mertz PM, Bilevich ED, Cazzaniga AL, Eaglstein WH.Early debridement of second-degree burn wounds enhances the63. Sauder DN, Kilian PL, McLane JA, Quick TW, Jakubovic H, Davisrate of epithelization-an animal model to evaluate burn woundSC, Eaglstein WH, Mertz PM. Interleukin-1 enhances epidermaltherapies. J Burn Care Rehabil 1996;17:558–61.wound healing. Lymphokine Res 1990;9:465–73.

84. nii-Amon-Kotei D, Thielen RG, Hofmann-von-herr S, Pieper WM.64. Mertz PM, Sauder DN, Davis SC, Kilian PL, Herron AJ, EaglsteinAbrasion method for the immediate management of surface ther-WH. IL-1 as a potent inducer of wound re-epithelization. Prog Clinmal injuries of childhood. Z Kinderchir Grenzgeb 1980;29:283–91.Biol Res 1991;365:473–80.

85. Mertz PM, Hebda PA, Eaglstein WH. A porcine model for evaluat-65. Barbul A. The effects of Interleukin 1 on the healing of spliting epidermal wound healing. In: Tumbleson ME, editor. Swinethickness donor sites. Reported at the 47th annual sessions of thein biomedical research. New York: Plenum Press, 1986: 291–302.forum on fundamental surgical problems at the clinical congress

of the American college of surgeons; 1991 Oct 20–25; Chicago 86. Hung VC, Lee JY, Zitelli JA, Hebda PA. Topical tretinoin and epithe-lial wound healing. Arch Dermatol 1989;125:65–9.(IL).

66. Chen JD, Lapiere JC, Sauder DN, Peavey C, Woodley DT. Interleu- 87. Mandy SH. Tretinoin in the preoperative and postoperative man-agement of dermabrasion. J Am Acad Dermatol 1986;15:878–9.kin-1 alpha stimulates keratinocyte migration through an epider-

mal growth factor/transforming growth factor-alpha-independent 88. Hevia O, Nemeth AJ, Taylor R. Tretinoin accelerates healing afterpathway. J Invest Dermatol 1995;104:729–33. trichoroacetic acid chemical peel. Arch Dermatol 1991;127:678–82.

89. Anthony J, Miller L, Dinehart SM. Topical tretinoin decreases67. Pierce GF, Tarpley JE, Yanagihara D, Mustoe TA, Fox GM, Thom-healing times of electroepilation-induced wounds. Dermatologicaason A. Platelet-derived growth factor (BB homodimer) trans-1991;183:129–31.forming growth factor beta 1 and basic fibroblastic growth factor

in dermal wound healing Am J Path 1992;140:1375–88. 90. Popp C, Kligman AM, Stoudemayer TJ. Pretreatment of photoaged


forearm skin with topical tretinoin accelerates healing of full- 112. Lyon RA, Renyolds TE. Promotion of healing by benzoyl peroxideand other agents. Proc Soc Exp Med 1929;27:122–4.thickness wounds. Br J Dermatol 1995;132:46–53.

91. Lawrence JE, Blake GB. A comparison of calcium alginate and 113. Lynch WS, Bailin PL. The promotion of wound healing followingscarlet red dressings in the healing of split thickness skin graft chemosurgery (Moh’s technique) by dressing with a lotion of ben-donor sites. Br J Plast Surg 1991;44:247–9. zoyl peroxide. J Dermatol Surg Oncol 1978;4:91–5.

92. Bettinger D, Gore D, Humphries Y. Evaluation of calcium alginate 114. Pace W. Treatment of cutaneous ulcers with benzoyl peroxide.for skin graft donor sites. J Burn Care Rehabil 1995;16:59–61. CMA J 1976;115:1101–6.

93. Rives JM, Pannier M, Castede JC, Martinot V, LeTouze A, Romana 115. Alvarez OM, Mertz PM, Eaglstein WH. Benzoyl peroxide and epi-MC, Guitard J, Bohbot S, Ebel C. Calcium alginate versus paraffin dermal wound healing. Arch Dermatol 1983;19:222–5.gauze in the treatment of scalp graft donor sites. Wounds 1997; 116. Bolton L, Oleniacz B, Constantine BO, Kelliher BO, Jensen D,9:199–205. Means B, Rovee D. Repair and antibacterial effects of topical

94. Basse P, Sim E, Lohman M. Treatment of donor sites-calcium antiseptic agents in vivo. In: Mailbach HI, Lowe NJ, editors. Modelsalginate versus paraffin gauze. Acta Chir Plast 1992;34:92–8. in dermatology. Basel: Karger, 1985: 145–58.

95. O’Donoghue JM, O’Sullivan ST, Beausang ES, Panchal JI, 117. Nance FC, Lewis VL, Hines JL, Barnett DP, O’Neill JA. AggressiveO’Shaughnessy M, O’Connor TP. Calcium alginate dressings pro- outpatient care of burns. J Trauma 1972;12:144–6.mote healing of split skin graft donor sites. Acta Chir Plast 1997; 118. Webber CE, Glanges E, Crenshaw CA. Treatment of second-degree39:53–5. burns: nitrofurazone, povidone-iodine, and silver sulfadiazine.

96. Attwood AI. Calcium alginate dressing accelerates split skin graft JACEP 1977;11:486–90.donor site healing. Br J Plast Surg 1989;42:373–9. 119. Lineaweaver W, Howard R, Soucy D, McMorris S, Freeman J, Cain

97. Young SR, Dyson M, Hickman R, Lang S, Osborn C. Comparison C, Robertson J, Rumley T. Topical antimicrobial toxicity. Archof the effects of semi occlusive polyurethane dressings and hydro- Surg, 1985;120:267–70.colloid dressings on dermal repair: cellular changes. J Invest Der- 120. Kaiser W, von der Lieh H, Potel J, Heymann H. Experimentalmatol 1991;97:586–92. study of the local application of silver sulfadiazine, cefsulodin

98. Wyatt D, McGowan DN, Najarian MP. Comparison of a hydrocol- and povidone-iodine in burns. Infection 1984;12:31–5.loid dressing and silver sulfadiazine cream in the outpatient man- 121. Branemark PI, Albrektsson B, Lindstrom J, Lundborg G. Localagement of second degree burns. J Trauma 1990;30:857–65. tissue effects of wound disinfectants. Acta Chir Scand Suppl 1966;

99. Afilalo M, Dankoff J, Guttman A, Lloyd J. DuoDerm hydroactive 357:166–76.dressing versus silver sulphadiazine/ bactigras in the emergency 122. Brennan SS, Leaper DJ. The effect of antiseptics on the healingtreatment of partial skin thickness burns. Burns 1992;4:313–6. wound: a study using the rabbit ear chamber. Br J Surg 1985;72:

100. Hermans MH, Hermans RP. Preliminary report on the use of a 780–2.new hydrocolloid dressing in the treatment of burns. Burns Incl 123. Constable J. Comparative effects of Betadine ointment (povidone-Therm Inj 1984;11:125–9. iodine) and other topical agents on epidermal regeneration in

101. Hermans MH. Hydrocolloid dressing (DuoDerm) for the treatment rabbits. In: Proceedings from the Symposium Sponsored by theof superficial and deep partial thickness burns. Scand J Plast Department of Surgery; Durham (NC): 1974.Reconstr Surg Hand Surg 1987;21:283–5. 124. Jeffords JW, Hagerty RF. The healing of donor sites. Ann Surg

102. Davis SC, Mertz PM, Eaglstein WH. Second degree burn healing: 1957;145:169–74.the effect of occlusive dressing and a cream. J Surg Res 1990;48: 125. Frenkil J, Fishel ER. The use of nitrofurazone preparations in245–8. industrial practice. Indust Med Surg 1970;39:54–7.

103. Mandy SH. A new primary wound dressing made of polyethylene 126. Miller SF. Outpatient management of minor burns. Am Fam Physi-oxide gel. Dermatol Surg Oncol 1983;9:153–5. cian 1977;16:167–72.

104. Alvarez OM, Hefton JM, Eaglstein WH. Healing wounds: occlusion 127. McLinn S. A bacteriologically controlled, randomized study com-or exposure. Inf Surg 1984;173–81. paring the efficacy of 2% mupirocin ointment (Bactroban) with

105. Gilbert EC, Schenk WN, Upman PJ. Hydrogel dressings II. Healing oral erythromycin in the treatment of patients with impetigo. Jof full thickness skin wounds in swine; treatment with a new non- Am Acad Dermatol 1990;22:883–5.occlusive hydrogel absorbent dressing. Wounds 1990;2:56–63. 128. Eells LD, Mertz PM, Piovanetti Y, Pekoe GM, Eaglstein WH. Topical

106. Siim E, Leicht P, Strensen B. Omiderm treatment of scalds in antibiotic treatment of impetigo with mupirocin. Arch Dermatolchildren. Burns Incl Therm Inj 1989;15:4–6. 1986;122:1273–6.

107. Weber RS, Hankins P, Limitone E, Callender D, Frankenthaler 129. Villiger JW, Robertson WD, Kanji K, Ah Chan M, Fetherston J,RM, Wolf P, Goepfert H. Split thickness skin graft donor site Hague IK, Haycock D, Hunter P. A comparison of the new topicalmanagement. A randomized prospective trial comparing a hydro- antibiotic mupirocin (‘Bactroban’) with oral antibiotics in thephilic polyurethane absorbent foam dressing with a petrolatum treatment of skin infections in general practice. Curr Med Resgauze dressing. Arch Otolaryngol Head Neck Surg 1995;121: Opin 1986;10:339–45.1145–1149. 130. Mertz PM, Dunlap BW, Eaglstein WH. The effects of Bactroban

108. Sailsbury RE, Bevin AG, Dingeldein GP, Grisham J. A clinical and ointment on epidermal wound healing in partial thickness wounds.laboratory evaluation of polyurethane foam: a new donor site In: Dobson RL, Leyden JJ, Noble WC, Price JD, editors. Bactrobandressing. Arch Surg 1979;114:1188–92. (Mupirocin) Proceedings of an International Symposium; 1984

May 21–22; Nassau, Bahamas, Amsterdam: Excerpta Medica, 1985:109. Smack DP, Harrington AC, Dunn C, Howard RS, Szkutnik AJ,Krivda SJ, Calswell JB, James WD. Infection and allergy incidence 211–5.in ambulatory surgery patients using white petrolatum vs. bacitra- 131. BalinAK,LeongI,CarterDM.Effect ofmupirocinonthegrowthandcin ointment. A randomized controlled trial. JAMA 1996;276:972– lifespan of human fibroblasts. J Invest Dermatol 1987;88:736–40.7. 132. White AR, Beale AS, Boon RJ, Griffin KE, Masters PJ, Sutherland

110. Watcher MA, Wheeland RG. The role of topical agents in the R. Antibacterial activity of mupirocin. The effects of Bactrobanhealing of full thickness wounds. J Dermatol Surg Oncol 1989;15: ointment on epidermal wound healing in partial thickness wounds.1188–95. In: Dobson RL, Leyden JJ, Noble WC, Price JD, editors. Bactroban

(Mupirocin) Proceedings of an International Symposium; 1984111. Cooper ML, Boyce ST, Hansbrough JF, Foreman TJ, Frank, DH.

Cytotoxicity to cultured human keratinocytes of topical antimicro- May 21–22; Nassau, Bahamas, Amsterdam: Excerpta Medica, 1985:19–36.bial agents. J Surg Res 1990;48:190–5.


133. Boyce ST, Warden GD, Holder IA. Non-cytotoxic combinations of cin on cultured human skin fibroblasts: relevance to wound heal-ing. J Dermatol 1992;19:664–6.topical antimicrobial agents for use with cultured skin substitutes.

Antimicrobial Agents Chemother 1995;39:1324–8. 156. Bhora FY, Dunkin BJ, Batzri S, Aly HM, Bass BL, Sidawy AN,134. Fuscher B. Organ fur amtliche und pracktische arzte Munch. Med Harmon JW. Effect of growth factors on cell proliferation and

Wochenschr 1906;42:2041–7. epithelilization in human skin. J Surg Res 1995;59:236–44.135. Davis JS. A further note on the clinical use of scarlet red and its 157. Robson MC, Philips LG, Thomason A, Altrock BW, Pence PC,

component, amidoazotoluol, in stimulating the epithelialization Heggers JP, Johnston AF, McHugh TP, Anthony MS, Robson LE.

of granulating surfaces. Ann Surg 1911;53:702–19. Recombinant human platelet derived growth factor-BB for thetreatment of chronic pressure ulcers. Ann Plast Surg 1992;29:136. Davis JS. The effect of scarlet red, in various combinations upon

the epithelialization of granulating surfaces. Ann Surg 1910;51: 193–201.40–51. 158. Rees RS, Robson MC, Smiell JM, Perry BH, the Pressure Ulcer

137. Morris WT, Lamb AM. Painless split skin donor sites: a controlled Study Group. Belcaplermin gel in the treatment of pressure ulcers.double blind trial of OpSite, scarlet red and bupivacaine 1990;60: A phase II randomized, double blind, placebo-controlled study.617–20. Wound Rep Reg 1999;7:141–7.

138. Prasad JK, Feller I, Thompson PD. A prospective controlled trial 159. Steed DL. Clinical evaluation of recombinant human platelet-of Biobrane versus scarlet red on skin graft donor areas. J Burn derived growth factor for the treatment of lower extremity dia-Care Rehabil 1987;8:384–6. betic ulcers. Diabetic Ulcer Study Group. J Vasc Surg 1995;21:

79–81.139. Zapata-Sirvent R, Hansbrough JF, Carroll W, Johnson R, WakimotoA. Comparison of Biobrane and scarlet red dressings for treatment 160. Mustoe TA, Cutler NR, Allman RM, Goode PS, Deuel TF, Prauseof donor site wounds. Arch Surg 1985;120:743–5. JA, Bear M, Serdar CM, Pierce GF. A Phase II study to evaluate

recombinant platelet-derived growth factor-BB in the treatment140. Gemberling RM, Miller TA, Caffee H, Zawacki BE. Dressing com-parison in the healing of donor sites. J Trauma 1976;16:812–4. of stage 3 and 4 pressure ulcers. Arch Surg 1994;129:213–9.

161. Danilenko DM, Ring BD, Tarpley JE, Morris B, Van GY, Morawiecki141. Salisbury RE, Bevin AG, Dingeldein P, Grisham J. A clinical andlaboratory evaluation of a polyurethane foam. Arch Surg 1979; A, Callahan W, Goldenberg M, Hersenson S, Pierce GF. Growth

factors in porcine full and partial thickness burn repair. Am J114:1188–92.Pathol 1995;147:1661–275.142. Roesel JF, Nanny LB. Assessment of differential cytokine effects

on angiogenesis using an in vivo model of cutaneous wound repair. 162. Lepisto J, Laato M, Niinikoski J. Effects of homodimeric isoformsof platelet derived growth factor on wound healing in the rat. JJ Surg Res 1995;58:449–59.Surg Res 1992;53:596–601.143. Thornton JW, Hess CA, Cassingham V, Bartlett RH. Epidermal

growth factor in the healing of second-degree burns: a controlled 163. Pierce GF, Mustoe TA, Senior RM, Reed J, Griffin GL, Thomason A,Deuel TF. In vivo incisional wound healing augmented by plateletanimal study. Burns Incl Therm Inj 1982;8:156–60.derived growth factor and recombinant c-sis gene homodimeric144. Franklin JD, Lynch JB. Effects of topical applications of epidermalproteins. J Exp Med 1988;167:974–87.growth factor on wound healing. Experimental study on rabbit

ears. Plast Reconstr Surg 1979;64:766–70. 164. Pierce GF, Tarpley JE, Yanagihara D, Mustoe TA, Fox GM, Thom-ason A. Platelet derived growth factor (BB homodimer), trans-145. Rheinwald JG, Green H. Epidermal growth factor and the multipli-forming growth fator-beta 1 and basic fibroblast growth factor incation of cultured human epidermal keratinocytes. Nature 1977;dermal wound healing. Am J Pathol 1992;140:1375–88.265:421–4.

165. Hill E, Turner-Beatty M, Groteweil M, Fosha-Thomas S, Cox C,146. Schmidt JA, Mizel SB, Cohen D, Grien I. Interleukin 1, a potentTurman C, Drees D, Baird L, Maratea D, Tucker R. The effects ofregulator of fibroblast proliferation. J Immunol 1982;128:2177–PDGF on the healing of fulll thickness wounds in hairless guinea82.pigs. Comp Biochem Physiol A (England) 1991;100:365–70.147. Ristow HJ. A major factor contributing to epidermal proliferation

166. Senior RM, Griffin GL, Huang JS, Walz DA, Deuel TF. Chemotacticin inflammatory skin diseases appears to be interleukin or a re-activity of platelet � granules proteins for fibroblasts. J Cell Biollated protein. Proc Natl Acad Sci USA 1987;84:1940–4.1983;96:382–5.148. Sauder DN, Stanulis-Prager BM, Gilchrist BA. Autocrine growth

167. Kuhler N, Lipton A. Platelets as a source of fibroblast growthstimulation of human keratinocyte by epidermal cell derived thy-promoting activity. Exp Cell Res 1974;87:297–301.mocyte activating factor: implication of skin aging. Arch Dermatol

Res 1988;280:71–6. 168. Kaplan DR, Chao FC, Stiles CD, Antoniades HN, Scher CD. Platelet� granules contain a growth factor for fibroblasts. Blood 1979;149. Postlethwaite AE, Lachman LB, Kang AH. Induction of fibroblast53:1043–52.proliferation by interleukin 1 derived from human monocytic leu-

kemia cells. Arthritis Rheum 1984;27:995–1001. 169. Ahonen J, Jiborn H, Zederfeldt B. Hormone influence on woundhealing. In: Hunt TK, editor. Wound healing and wound infection.150. Matsushima K, Bano M, Hidwell WR, Oppenheim JJ. InterleukinTheory and surgical practice. New York: Appleton-Century-1 increases collagen type IV production by murine mammaryCrofts,1977: 99–105.epithelial cells. J Immunol 1985;134:904–9.

170. Wells GC. The effect of hydrocortisone on standardized skin sur-151. Hebda PA, Klingbeil CK, Abraham JA, Fiddes JC. Basic fibroblastface trauma. Br J Dermatol 1957;69:11–18.growth factor stimulation of epidermal wound healing in pigs. J

Invest Dermatol 1990;95:626–31. 171. Rio J-PA, Cohen JR, Johnson H Jr. Factors influencing wounddehiscence. Am J Surg 1992;163:324–30.152. Tsuboi R, Sato C, Shi CM, Ogawa H. Stimulation of keratinocyte

migration by growth factors. J Dermatol 1992;19:652–3. 172. Alvarez OM, Levendorf KD, Smerbeck RV, Mertz PM, EaglsteinWH. Effect of topically applied steroidal and nonsteroidal anti-153. Imaizumi T, Jean-Louis F, Dubertret ML, Bailly C, Cicurel L,inflammatory agents on skin repair and regeneration. Fed ProcPetchot-Bacque JP, Dubertret L. Effect of human basic fibroblast1984;43:2793–8.growth factor on fibroblats proliferation, cell volume, collagen

lattice contraction: in comparison with acidic type. J Dermatol 173. Nieder R, Schopf E. Effects of corticosteroids on wound healing.In: Christophers E, editor. Topical corticosteroid therapy: a novelSci 1996;11:134–41.approach to safer drugs. New York: Raven Press Inc, 1988: 71–3.154. Gospodarowicz D, Bialecki H, Thakral TK. The angiogenic activity

of the fibroblast and epidermal growth factor. Exp Eye Res 1979; 174. Ponec M, Kempenaar JA, Van Der Meulen G, Bachra BN. Effects28:501–14. of glucocorticoids on cultured skin fibroblasts-IV. Biochem Phar-

macol 1979;28:2777–83.155. Saski T. The effects of basic fibroblast growth factor and doxorubi-


175. Ponec M, de Hass C, Kempenaar JA, Bachra BN. Effects of gluco- injuries through the use of prompt eschar excision. Ann Surg1988;208:577–85.corticoids on cultured skin fibroblasts. Arch Dermatol Res 1979;

266:75–82. 187. Engrav LH, Heimbach DM, Reus JL, Harnar TJ, Marvin JA. Earlyexcision and grafting vs. nonoperative treatment of burns of inde-176. Berliner DL, William RJ, Taylor GN, Nabors CJ. Decreased scar

formation with topical corticosteroid treatment. Surgery 1967;61: terminate depth: a randomized prospective study. J Trauma 1983;23:1001–4.619–25.

177. Altmeyer P, Buhles N. Tolerance to corticoids? Guinea pig epithe- 188. Gray DT, Pine RW, Harnar TJ, Marvin JA, Engrav LH, HeimbachDM. Early surgical excision versus conventional therapy in pa-lium as an experimental system. Arch Dermatol Res 1981;271:3–9.

178. Alvarez OM, Iuzzolino A, O’Hare W, Gilbreath RL. Testosterone tients with 20–40 percent burns. Am J Surg 1982;144:76–9.189. Burke JF, Bondoc CC, Quinby WC. Primary burn excision andincreases collagen deposition in experimentally induced granula-

tion tissue. Fed Proc 1981;40:343. [Abstract] immediate grafting: a method shortening illness. J Trauma 1974;14:389–94.179. Falanga V, Greenberg AS, Zhou L. Stimulation of collagen synthesis

by the anabolic steroid stanozolol. J Invest Dermatol 1998;111: 190. Thompson P, Herndon DN, Abston S, Rutan T. Effect of earlyexcision on patients with major thermal injury. J Trauma 1987;1193–7.

180. Ponec M, de Haas C, Kempenaar JA, Bachra BN. Effects of gluco- 27:205–7.191. Zawacki BE. The reversal of capillary stasis and prevention ofcorticosteroids on cultured human skin fibroblasts. V. Influence

of anabolic steroids on the inhibitory effects of clobetasol-17- necrosis in burns. Ann Surg 1974;180:98–102.192. Hansbrough JF, Herndon DN, Heimbach DM, Solem LD, Gamellipropionate on cell proliferation and collagen synthesis. Arch Der-

matol Res 1979;266:75–82. RL, Tompkins RG. Accelerated healing and reduced need for graft-ing in pediatric patients with burns treated with arginine-glycine-181. Eaglstein WH, Mertz PM. ‘Inert’ vehicles do affect wound healing.

J Invest Dermatol 1980;74:90–1. aspartic acid peptide matrix. RGD Study Group. J Burn CareRehabil 1995;16:377–87.182. Schmidt JM, Greenspoon JS. Aloe vera dermal wound gel is associ-

ated with a delay in wound healing. Obstet Gynecol 1991;78:115–7. 193. Mertz PM, Davis SC, Franzen L, Uchima FD, Pickett MP, Piersch-bacher MD, Polarek JW. Effects of an arginine-gylcine-aspartic183. Heggers JP, Elzaim H, Garfield R, Goodheart R, Listengarten D,

Zhao J, Phillips LG. Effect of the combination of aloe vera, nitro- acid peptide containing artificial matrix on epithelial migrationin vitro and experimental second-degree burn wound healing inglycerin, and L-Name on wound healing in the rat excisional

model. J Altern Complement Med 1997;3:149–53. vivo. J Burn Care Rehabil 1996;17:199–206.194. Warren WC, Mustoe TA, Glenn KC. Tissue repair by thrombin-184. Chitra P, Sajithal GB, Chandrakasan G. Influence of aloe vera on

the healing of dermal wounds in diabetic rats. J Ethnopharmacol derived peptides in the rat. Pept Res 1992; 5:331–5.195. Cooper ML, Hansbrough JF, Polarek JW. The effect of an arginine-1998;59:195–201.

185. Chitra P, Sajithal GB, Chandrakasan G. Influence of Aloe vera on glycine-aspartic acid peptide and hyuronate synthetic matrix onepithelialization of meshed skin graft intericews. J Burn Carecollagen characteristics in healing dermal wounds in rats. Mol

Cell Biochem 1998;181:71–6. Rehabil 1996;17:108–16.196. Pierschbacher MD, Puoslahti E. Cell attachment activity of fibro-186. Tompkins RG, Remensnyder JP, Burke JF, Tompkins DM, Hilton

JF, Schoenfeld DA, Behringer GE, Bondoc CC, Briggs SE, Quinby nectin can be duplicated by small synthetic fragments of themolecule. Nature 1984;309:30–3.WC. Significant reductions in mortality for children with burn

Documents

THE PIG AS A MODEL FOR HUMAN WOUND HEALING