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Original Article |

Transforming Growth Factor β3 Promotes Fascial Wound Healing in a New Animal Model FREE

John W. Tyrone, MD; Jeffrey R. Marcus, MD; Steven R. Bonomo, MD; Jon E. Mogford, PhD; Yuping Xia, PhD; Thomas A. Mustoe, MD
[+] Author Affiliations

From the Department of Surgery, University of California, Davis[[ndash]]East Bay, Oakland (Dr Tyrone), Division of Plastic and Reconstructive Surgery, Northwestern University Medical School, Chicago, Ill (Drs Marcus, Mogford, Xia, and Mustoe), and Department of Surgery, Rush University Medical School, Chicago, Ill (Dr Bonomo).


Arch Surg. 2000;135(10):1154-1159. doi:10.1001/archsurg.135.10.1154.
Text Size: A A A
Published online

Hypothesis  Transforming growth factor β3 (TGF-β3) promotes fascial wound healing in a new animal model, as measured by wound breaking strength, collagen deposition, and cellular proliferation.

Design/Intervention  Bilateral, longitudinal incisions were made in the anterior rectus sheaths of 24 male New Zealand white rabbits. One incision was treated with 1 µg of TGF-β3; the contralateral incision served as a control. The wounds were harvested at 1, 2, 3, 4, 6, and 8 weeks after creation ("wounding").

Main Outcome Measures  Wound tissue was tested for breaking strength using a tensiometer and processed for histological examination of collagen deposition and cellular proliferation at all time points after wounding. Collagen deposition and cellular proliferation were measured in histological cross sections of wounds with Masson trichrome staining and proliferating cell nuclear antigen immunohistochemistry, respectively.

Results  At all time points after wounding, treatment with TGF-β3 significantly increased the wound breaking strength (up to 138%) and collagen deposition (up to 150%) over the control group. Cellular proliferation was increased during the first 3 weeks after wounding (up to 147%), but returned to baseline levels by the fourth week.

Conclusions  Transforming growth factor β3 promotes fascial wound healing. In this new animal model of fascial wound healing, TGF-β3 increased fascia breaking strength, collagen deposition, and cellular proliferation. These results are similar to findings in cutaneous wound models and demonstrate, for the first time, a pharmacologic agent to accelerate fascial healing.

Figures in this Article

SURGEONS have long recognized that the strength of abdominal wound closure relies on restoration of fascial integrity. Inadequate fascial healing can result in a number of potentially serious complications, including fascial dehiscence, incisional hernia formation, and even evisceration. Despite numerous research studies seeking to optimize outcomes, the incidence of wound disruption has changed little in the past 40 years.1 Studies examining mechanical factors in wound closure,24 technical variations in closure,57 incision orientation,8 suture material,9,10 and wound physiology11,12 have resulted in equivocal results with regard to the enhancement of healing strength and the reduction of dehiscence and herniation. Other than vitamin supplements for the nutritionally deficient, no pharmacological agent or technique has been shown to significantly improve fascial wound healing.13

In the early 1950s, experimental evidence first demonstrated prolonged healing in fascia relative to skin and other tissues.14 In cutaneous wounds, inflammatory cells migrate from local blood vessels, and fibroblasts migrate from the wound margin to almost immediately influence healing. In contrast, inflammatory cells and fibroblasts must, to a greater extent, migrate through surrounding tissues to the wound area in healing fascia due to its limited cellularity and vascularity. Other studies demonstrated tissue-specific differences such as longer cell-doubling times, larger cell volume, and higher glucose requirements in fascial fibroblasts.15 As a result of these differences, skin requires 6 weeks to regain 60% of its unwounded strength, while similar percentage gains are not achieved in fascia until after 14 weeks.14

The transforming growth factor betas (TGF-β1,2,3 isoforms), considered to be the main orchestrators of wound healing, affect a broad range of activities in repair of injured tissue, including fascia. Transforming growth factor β has direct effects on target cells and indirect effects on the production and release of other growth factors involved in wound healing.1619 In vivo and in vitro studies have shown that TGF-β is chemotactic and mitogenic for fibroblasts and endothelial cells, and is the most potent stimulator of procollagen alpha 1[I] production by fibroblasts.2022 Of the 3 mammalian isoforms, the TGF-β3 isoform is the most potent with regard to these characteristics.23 Based on our previous work with TGF-β,16,24,25 we hypothesize that homologous stimuli drive wound healing in both skin and fascia, and that TGF-β3 will accelerate fascial healing.

It is the purpose of this work to examine the role of growth factor–stimulated healing in a fascial model. We introduce a modification of Lichtenstein and coworkers' rabbit model for fascial healing, which we believe is an ideal model for the study of recombinant growth factors in fascial healing.26 The outcome measures investigated in this study included wound breaking strength, collagen deposition, and cellular proliferation in response to TGF-β3 stimulation of wound healing.

STUDY DESIGN

Twenty-four New Zealand white rabbits were wounded as described below. The wounds were treated with a single dose of 1-µg TGF-β3 in methylcellulose gel or vehicle alone at the time of wounding. This dose has been previously proven optimal in incisional and excisional wounds of similar size.25 The fascial incisions were harvested at 1, 2, 3, 4, 6, and 8 weeks after wounding; 4 animals were used at each time point. Weeks 5 and 7 were not tested to conserve resources. Each incision was analyzed for breaking strength, collagen deposition, and cellular proliferation, and the results were averaged for each animal. Animals were housed under standard conditions and fed ad libitum under an experimental protocol approved by the Northwestern University Animal Care and Use Committee.

All wounds were created and harvested in a matched fashion, and the data collected in a manner to allow paired analysis, with each animal serving as its own control. A paired, 2-tailed t test was performed at each time point for wound breaking strength, collagen deposition, and cellular proliferation. P<.05 was considered significant. Statistical analysis was performed using SPSS 8.0 software for Windows (SPSS Inc, Chicago Ill).

ANIMAL MODEL

Adult male rabbits, weighing 2 to 2.5 kg, were anesthetized with intramuscular injection of 60-mg/kg ketamine hydrochloride and 5-mg/kg xylazine hydrochloride, and prophylactically treated with 1 million units of intramuscular penicillin G prior to making the skin incision. The abdominal area was shaved and prepared with povidone-iodine solution. Using a sterile technique, a longitudinal, midline skin incision was made from the xiphoid process to 2 cm above the pubic tubercle, down to the level of the linea alba. Soft tissues were dissected from the anterior aspect of both rectus sheaths, in the avascular prefascial plane. Bilateral, longitudinal, 6-cm incisions were made in each rectus sheath under surgical loupe magnification, taking care to not injure the underlying muscle (Figure 1). The incisions were randomized to receive either 1 µg of TGF-β3 isoform in methylcellulose vehicle or vehicle alone. Vehicle was previously compared with nontreated control, and no difference in healing was found (unpublished data). The fascial incisions were closed with a running 6-0 nylon suture, and the skin was closed with a 4-0 nylon suture.

Place holder to copy figure label and caption
Figure 1.

Fascial wound model. The rabbit's anterior rectus fascia is exposed through a midline skin incision. Bilateral, longitudinal rectus fascia incisions (arrows) are made each side of midline. One incision serves as the test wound, and the contralateral side serves as the control wound.

Graphic Jump Location
WOUND TENSILE TESTING

At 1, 2, 3, 4, 6, and 8 weeks after wounding, the animals were humanely killed and the anterior rectus fascia harvested. After removing the nylon fascial suture, a template with parallel surgical blades was used to excise 5-mm strips perpendicular to the incision. Eight strips were taken from each wound; 6 strips were used for breaking strength testing, and 2 for histological analysis. The maximum load tolerated by wound strips prior to breaking was measured in newtons with a tensiometer (Instron Inc, Canton, Mass). The 2 remaining strips were formalin fixed and embedded in paraffin for histological evaluation.

COLLAGEN DEPOSITION

Histological slides were prepared with Masson trichrome staining for evaluation of collagen deposition (Figure 2). Because of the sensitivity of trichrome staining to errors in technique and to reduce variations in staining between specimens, all tissue was prepared and stained together in mass. Slides were viewed under a standard light microscope at ×20 power. Using a grading scale of 0 to 4, two blinded observers (J.W.T. and J.R.M.) graded the collagen deposition of treated and untreated specimens. In addition, computerized histological analysis was performed using a software program (NIH Image; National Institutes of Health, Bethesda, Md) to obtain semiquantitative results. Briefly, digital images were captured using a microscope (Nikon Axioscope; Nikon Inc, Melville, NY) equipped with a color digital camera. These images were imported into a personal computer running the NIH Image software. This software program allows quantification of specific histological tissues by measurement of individual pixels, based on intensity and color, allowing the user to select a specified stain and determine the relative area of a slide that the stain occupies.

Place holder to copy figure label and caption
Figure 2.

Histological analysis of control (A, C, and E) and transforming growth factor β3–treated (B, D, and F) wounds at 2, 4, and 8 weeks after wounding. The unwounded margins of the native fascia (NF) are seen laterally as a homogeneous blue band, whereas the media fascial incisions (IN) are more heterogeneous in appearance. Collagen is stained intensely blue (trichrome stain, original magnification ×5).

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IMMUNOHISTOCHEMISTRY: PROLIFERATIVE CELLULAR FRACTION

Histological slides were prepared by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) to determine cellular proliferation, and counted by 2 blinded observers (Figure 3). Briefly, proliferating cells were identified using a monoclonal antibody to the PCNA (Calbiochem-Novabiochem, San Diego, Calif). This 37-kd protein has been used as a reliable marker for the determination of proliferative cellular fractions in hematological and solid malignant neoplasms as well as benign tumors.27 In accord with our previous dilution curve development, the primary antibody (1:100 dilution) was applied to the slides and incubated at room temperature overnight. Rabbit-absorbed, biotinylated secondary antibody was applied (Super Sensitive Detection System; Biogenix, San Ramon, Calif) and incubated for 20 minutes at 37°C. Streptavidin-horseradish peroxidase complex was applied and incubated at 37°C for 20 minutes. 3-Amino-9-ethylcarbazole (AEC) chromogen labeled the nuclei of proliferating cells in red. Slides were counterstained and mounted with aqueous medium in standard fashion. The specimens were analyzed by 2 blinded observers and reported as nuclear counts per high-power field. All spindle-shaped (representing fibroblasts) and round nuclei (representing inflammatory cells) up to 5 mm on each side of the incision were counted. The final results were expressed as percentage change vs controls.

Place holder to copy figure label and caption
Figure 3.

Histological specimens stained for proliferating cells in control (A) and transforming growth factor β3–treated (B) wounds at 1 week after wounding. Proliferating cells are stained red-orange (proliferating cell nuclear antigen stain, original magnification ×100).

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TENSILE TESTING

The average breaking strength of 6 test samples was compared with that of 6 control samples from the same animal, 4 animals per time point (Table 1). A statistically significant increase in wound breaking strength was seen with TGF-β3 treatment as early as 1 week after wounding and continued throughout the study. The wound breaking strength of the TGF-β3–treated specimens was augmented 22% at week 1, peaked at 39% 2 weeks after wounding, and stabilized at 27% increase of control by 6 weeks (P<.01) (Figure 4A). At the latest time point, 8 weeks after wounding, the increase in breaking strength of the test group continued to demonstrate a 27% increase over the control group.

Place holder to copy figure label and caption
Figure 4.

Percentage increase in average breaking strength (A) and collagen content (B) of transforming growth factor β3–treated specimens over control specimens at 1, 2, 3, 4, 6, and 8 weeks after wounding. Bars represent SD.

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COLLAGEN CONTENT

Collagen content as evaluated by blinded observers and computer-aided histological analysis closely paralleled the breaking strength results (Figure 4B). Blinded observation demonstrated a 25% increase in collagen deposition with TGF-β3 treatment at week 1, peaking at 50% increase during week 3, and stabilizing with a 25% increase over the control specimens. Computer-aided histological analysis demonstrated a similar increase with TGF-β3 treatment over the control condition (P<.05). At each time point, the observational results correlated closely with the computer analysis.

CELLULAR PROLIFERATION

Cellular proliferation as determined by PCNA staining was significantly increased for the first 3 weeks of testing (P<.05). Proliferation was increased in both spindle-shaped cells (representing fibroblasts) and round cells (representing all other cells) equally. No significant difference was seen in proliferation between cell types. At 1 week after wounding, total PCNA counts were increased over control (47%). A 21% and 9% gain in cellular proliferation was seen in treated specimens vs control specimens at 2 and 3 weeks, respectively. At 4 weeks, the PCNA counts returned to baseline, with no statistical difference from control (Figure 5).

Place holder to copy figure label and caption
Figure 5.

Percentage increase in cellular proliferation (by proliferating cell nuclear antigen staining) of transforming growth factor β3–treated specimens over control specimens at 1, 2, 3, and 4 weeks. Results are significantly increased for weeks 1, 2, and 3. No significant difference was seen after week 3. Bars represent SD.

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Our results support the hypothesis that TGF-β3 augments fascial wound healing and demonstrates, for the first time, a pharmacologic agent to accelerate fascial healing. In this new animal model of fascial wound healing, TGF-β3 increased fascia breaking strength, collagen deposition, and cellular proliferation. These results are consistent with results of previous studies examining the effects of TGF-β3 in cutaneous wound models.23,25 However, the sustained increase in fascia strength over the entire 8 weeks of the study is noteworthy and suggests potential clinical utility.

A paucity of fascial wound healing research has resulted in the development of relatively few animal models for testing fascial healing. Using a modification of the fascial wound model created by Lichtenstein et al26 in 1970, we have designed a new model of fascial wound healing that we believe to be useful and clinically relevant. In short, bilateral longitudinal incisions are made in the anterior rectus sheath of New Zealand white rabbits. This method allows easy and precise harvesting of one fascial layer, which is consistently uniform in thickness cephalad to caudad as well as from one animal to another. Accurate evaluation of various measures of fascial wound healing is easily attainable with this model, and bilateral incision allows the animal to serve as its own control. In addition, wounding only the anterior sheath averts potential complications from entering the abdominal cavity, such as intra-abdominal adhesions, infection, or ileus.

In this study, treatment with TGF-β3 was effective in increasing the wound breaking strength between 22% and 39% over the control condition at all time points. An interesting and unexpected result of this study was the finding that the control specimens never attained the same level of wound strength or collagen content as the treated specimen. Although periods later than 8 weeks have not been examined and this finding may be strictly related to the chronology of wound repair, it suggests that exogenously applied growth factor can actually allow a wounded tissue to heal stronger than normal wound healing. In contrast to previous studies that have shown that wounds regain maximally only 80% of the breaking strength of unwounded tissue,28 tensile testing performed on unwounded tissue displayed a breaking strength similar to (22-25 N) that which is required to break the TGF-β3–treated specimens at 8 weeks after wounding (approximately 90% of unwounded strength for TGF-β3–treated vs 65% for control). These results suggest that modulation with growth factors can assist a healing tissue in attaining closer to 100% of the prewound strength.

Collagen deposition as evaluated by computerized image analysis was effective for estimating the amount of collagen present in histological specimens. The amount of collagen present as determined by computerized histological analysis closely paralleled the blinded observer results and correlated closely with the breaking strength. Only during the first 3 weeks after wounding did the collagen deposition mildly overestimate the breaking strength results. We believe this is likely due to poor cross-linking of collagen fibers in the early stages of wound healing, resulting in excess collagen with little tensile strength.

The results of the cellular proliferation by PCNA counts demonstrated that initial cellular proliferation is enhanced. Although no difference in proliferation was seen between spindle-shaped cells and round cells, the increase in total cellular proliferation was highly significant. As expected from a single dose of growth factor, the increase in proliferation was temporary, returning to basal levels by 4 weeks after wounding. Use of a delayed-release formulation may be of benefit in the clinical setting by prolonging the stimulatory effect, and further increasing the cellular proliferation and total collagen deposition.

The ability to augment fascial healing with growth factors has clinical potential in high-risk abdominal wall closures and other fascial defects, as well as routine herniorrhaphy. As early as 1 week after wounding, TGF-β3 treatment significantly increased the wound breaking strength. This rapid gain in strength may help augment an incision at a time when the tissues are at their weakest and the suture is degrading. The sustained increase in collagen and breaking strength offers some evidence that TGF-β3 may also be able to counter the effects of poor tissue integrity, atrophy due to advanced age, or various disease states. Although no complications were noted in any of the animals, potential drawbacks of using TGF-β3 to augment fascial wound healing in humans may include development of intra-abdominal adhesion or increased scar formation. While not yet addressed in human subjects, postoperative peritoneal adhesion formation in animals treated with intra-abdominal injection of TGF-β has been minimal.29 In contrast to the other TGF-β isoforms, treatment with TGF-β3 exhibits no increased scar formation,25 and is therefore the most promising isoform for clinical use.

Another interesting use of growth factor therapy may be in combination with mesh. Synthetic materials are frequently used to reinforce hernia repairs, and the stimulatory effects of TGF-β3 could accelerate tissue incorporation of these materials. This may reduce the incidence of recurrent hernia formation due to dislodgment of the mesh during the early postoperative period, such as in laparoscopic herniorrhaphy, where the mesh is usually held in place by just a few stay sutures or staples. In addition, the increase in breaking strength seen with TGF-β3 in healing fascia may also allow the surgeon to choose absorbable mesh in instances where one otherwise might use permanent, nonabsorbable mesh, or even allow the surgeon to perform repairs without the use of mesh in cases that one might otherwise use it. Further work is needed to determine the most effective method of delivery, whether alone, with fascia or dermal allograft, or in combination with mesh, and clinical studies examining these points are warranted.

The TGF-β3 was supplied by David Cox, PhD, Novartis Pharma AG, Basel, Switzerland.

Reprints: Thomas A. Mustoe, MD, Division of Plastic and Reconstructive Surgery, Northwestern University Medical School, 675 N St Clair St, Suite 19-250, Chicago, IL 60611.

Carlson  MA Acute wound failure. Surg Clin North Am. 1997;77607- 636
Link to Article
Knolmayer  TJCornell  KMBowyer  MWMcCullough  JSKoenig  W Imbrication versus excision for fascial healing. Am J Surg. 1996;172506- 510
Link to Article
Poole  GVJ Mechanical factors in abdominal wound closure: the prevention of fascial dehiscence. Surgery. 1985;97631- 640
Stone  IKvon Fraunhofer  JAMasterson  BJ The biomechanical effects of tight suture closure upon fascia. Surg Gynecol Obstet. 1986;163448- 452
McNeil  PMSugerman  HJ Continuous absorbable vs interrupted nonabsorbable fascial closure: a prospective, randomized comparison. Arch Surg. 1986;121821- 823
Link to Article
Poole  GVJMeredith  JWKon  NDMartin  MBKawamoto  EHMyers  RT Suture technique and wound-bursting strength. Am Surg. 1984;50569- 572
Richards  PCBalch  CMAldrete  JS Abdominal wound closure: a randomized prospective study of 571 patients comparing continuous vs.interrupted suture techniques. Ann Surg. 1983;197238- 243
Link to Article
Greenall  MJEvans  MPollock  AV Midline or transverse laparotomy? a random controlled clinical trial: part I, influence on healing. Br J Surg. 1980;67188- 190
Link to Article
Osther  PJGjode  PMortensen  BBMortensen  PBBartholin  JGottrup  F Randomized comparison of polyglycolic acid and polygluconate sutures for abdominal fascial closure after laparotomy in patients with suspected impaired wound healing. Br J Surg. 1995;821080- 1082
Link to Article
Bucknall  TEEllis  H Abdominal wound closure—a comparison of monofilament nylon and polyglycolic acid. Surgery. 1981;89672- 677
Scher  KSScott-Conner  CEMontany  PF Effect of cephalosporins on fascial healing after celiotomy. Am J Surg. 1988;155361- 365
Link to Article
Taube  MEllis  H Mass closure of abdominal wounds following major laparotomy in jaundiced patients. Ann R Coll Surg Engl. 1987;69276- 279
Oberleas  DSeymour  JKLenaghan  RHovanesian  JWilson  RFPrasad  AS Effect of zinc deficiency on wound-healing in rats. Am J Surg. 1971;121566- 568
Link to Article
Douglas  DM The healing of aponeurotic incisions. Br J Surg. 1952;4079- 84
Link to Article
Lemonnier  FGautier  MWolfrom  CLemonnier  A Some metabolic differences between human skin and aponeurosis fibroblasts in culture. J Cell Physiol. 1980;104415- 423
Link to Article
Mustoe  TAPierce  GFThomason  AGramates  PSporn  MBDeuel  TF Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987;2371333- 1336
Link to Article
Pierce  GFMustoe  TALingelbach  J  et al.  Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol. 1989;109429- 440
Link to Article
Hom  DB Growth factors in wound healing. Otolaryngol Clin North Am. 1995;28933- 953
Roberts  ABSporn  MB Physiological actions and clinical applications of transforming growth factor-beta (TGF-β). Growth Factors. 1993;81- 9
Link to Article
Postlethwaite  AEKeski-Oja  JMoses  HLKang  AH Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 1987;165251- 256
Link to Article
Clark  RAMcCoy  GAFolkvord  JMMcPherson  JM TGF-β1 stimulates cultured human fibroblasts to proliferate and produce tissue-like fibroplasia: a fibronectin matrix-dependent event. J Cell Physiol. 1997;17069- 80
Link to Article
Murata  HZhou  LOchoa  SHasan  ABadiavas  EFalanga  V TGF-β3 stimulates and regulates collagen synthesis through TGF-β1–dependent and independent mechanisms. J Invest Dermatol. 1997;108258- 262
Link to Article
Cox  DA Transforming growth factor-beta 3. Cell Biol Int. 1995;19357- 371
Link to Article
Pierce  GFMustoe  TALingelbach  JMasakowski  VRGramates  PDeuel  TF Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1989;862229- 2233
Link to Article
Wu  LSiddiqui  AMorris  DECox  DARoth  SIMustoe  TA Transforming growth factor β3 (TGFβ3) accelerates wound healing without alteration of scar prominence: histologic and competitive reverse-transcription-polymerase chain reaction studies. Arch Surg. 1997;132753- 760
Link to Article
Lichtenstein  ILHerzikoff  SShore  JMJiron  MWStuart  SMizuno  L The dynamics of wound healing. Surg Gynecol Obstet. 1970;130685- 690
Jonsson  ZONubscher  U Proliferating cell nuclear antigen: more than a clamp for DNA polymerase. Bioessays. 1997;19967- 975
Link to Article
Witte  MBBarbul  A General principles of wound healing. Surg Clin North Am. 1997;77509- 528
Link to Article
Williams  RSRossi  AMChegini  NSchultz  G Effect of transforming growth factor beta on postoperative adhesion formation and intact peritoneum. J Surg Res. 1992;5265- 70
Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Fascial wound model. The rabbit's anterior rectus fascia is exposed through a midline skin incision. Bilateral, longitudinal rectus fascia incisions (arrows) are made each side of midline. One incision serves as the test wound, and the contralateral side serves as the control wound.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Histological analysis of control (A, C, and E) and transforming growth factor β3–treated (B, D, and F) wounds at 2, 4, and 8 weeks after wounding. The unwounded margins of the native fascia (NF) are seen laterally as a homogeneous blue band, whereas the media fascial incisions (IN) are more heterogeneous in appearance. Collagen is stained intensely blue (trichrome stain, original magnification ×5).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Histological specimens stained for proliferating cells in control (A) and transforming growth factor β3–treated (B) wounds at 1 week after wounding. Proliferating cells are stained red-orange (proliferating cell nuclear antigen stain, original magnification ×100).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Percentage increase in average breaking strength (A) and collagen content (B) of transforming growth factor β3–treated specimens over control specimens at 1, 2, 3, 4, 6, and 8 weeks after wounding. Bars represent SD.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Percentage increase in cellular proliferation (by proliferating cell nuclear antigen staining) of transforming growth factor β3–treated specimens over control specimens at 1, 2, 3, and 4 weeks. Results are significantly increased for weeks 1, 2, and 3. No significant difference was seen after week 3. Bars represent SD.

Graphic Jump Location

References

Carlson  MA Acute wound failure. Surg Clin North Am. 1997;77607- 636
Link to Article
Knolmayer  TJCornell  KMBowyer  MWMcCullough  JSKoenig  W Imbrication versus excision for fascial healing. Am J Surg. 1996;172506- 510
Link to Article
Poole  GVJ Mechanical factors in abdominal wound closure: the prevention of fascial dehiscence. Surgery. 1985;97631- 640
Stone  IKvon Fraunhofer  JAMasterson  BJ The biomechanical effects of tight suture closure upon fascia. Surg Gynecol Obstet. 1986;163448- 452
McNeil  PMSugerman  HJ Continuous absorbable vs interrupted nonabsorbable fascial closure: a prospective, randomized comparison. Arch Surg. 1986;121821- 823
Link to Article
Poole  GVJMeredith  JWKon  NDMartin  MBKawamoto  EHMyers  RT Suture technique and wound-bursting strength. Am Surg. 1984;50569- 572
Richards  PCBalch  CMAldrete  JS Abdominal wound closure: a randomized prospective study of 571 patients comparing continuous vs.interrupted suture techniques. Ann Surg. 1983;197238- 243
Link to Article
Greenall  MJEvans  MPollock  AV Midline or transverse laparotomy? a random controlled clinical trial: part I, influence on healing. Br J Surg. 1980;67188- 190
Link to Article
Osther  PJGjode  PMortensen  BBMortensen  PBBartholin  JGottrup  F Randomized comparison of polyglycolic acid and polygluconate sutures for abdominal fascial closure after laparotomy in patients with suspected impaired wound healing. Br J Surg. 1995;821080- 1082
Link to Article
Bucknall  TEEllis  H Abdominal wound closure—a comparison of monofilament nylon and polyglycolic acid. Surgery. 1981;89672- 677
Scher  KSScott-Conner  CEMontany  PF Effect of cephalosporins on fascial healing after celiotomy. Am J Surg. 1988;155361- 365
Link to Article
Taube  MEllis  H Mass closure of abdominal wounds following major laparotomy in jaundiced patients. Ann R Coll Surg Engl. 1987;69276- 279
Oberleas  DSeymour  JKLenaghan  RHovanesian  JWilson  RFPrasad  AS Effect of zinc deficiency on wound-healing in rats. Am J Surg. 1971;121566- 568
Link to Article
Douglas  DM The healing of aponeurotic incisions. Br J Surg. 1952;4079- 84
Link to Article
Lemonnier  FGautier  MWolfrom  CLemonnier  A Some metabolic differences between human skin and aponeurosis fibroblasts in culture. J Cell Physiol. 1980;104415- 423
Link to Article
Mustoe  TAPierce  GFThomason  AGramates  PSporn  MBDeuel  TF Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987;2371333- 1336
Link to Article
Pierce  GFMustoe  TALingelbach  J  et al.  Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol. 1989;109429- 440
Link to Article
Hom  DB Growth factors in wound healing. Otolaryngol Clin North Am. 1995;28933- 953
Roberts  ABSporn  MB Physiological actions and clinical applications of transforming growth factor-beta (TGF-β). Growth Factors. 1993;81- 9
Link to Article
Postlethwaite  AEKeski-Oja  JMoses  HLKang  AH Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 1987;165251- 256
Link to Article
Clark  RAMcCoy  GAFolkvord  JMMcPherson  JM TGF-β1 stimulates cultured human fibroblasts to proliferate and produce tissue-like fibroplasia: a fibronectin matrix-dependent event. J Cell Physiol. 1997;17069- 80
Link to Article
Murata  HZhou  LOchoa  SHasan  ABadiavas  EFalanga  V TGF-β3 stimulates and regulates collagen synthesis through TGF-β1–dependent and independent mechanisms. J Invest Dermatol. 1997;108258- 262
Link to Article
Cox  DA Transforming growth factor-beta 3. Cell Biol Int. 1995;19357- 371
Link to Article
Pierce  GFMustoe  TALingelbach  JMasakowski  VRGramates  PDeuel  TF Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1989;862229- 2233
Link to Article
Wu  LSiddiqui  AMorris  DECox  DARoth  SIMustoe  TA Transforming growth factor β3 (TGFβ3) accelerates wound healing without alteration of scar prominence: histologic and competitive reverse-transcription-polymerase chain reaction studies. Arch Surg. 1997;132753- 760
Link to Article
Lichtenstein  ILHerzikoff  SShore  JMJiron  MWStuart  SMizuno  L The dynamics of wound healing. Surg Gynecol Obstet. 1970;130685- 690
Jonsson  ZONubscher  U Proliferating cell nuclear antigen: more than a clamp for DNA polymerase. Bioessays. 1997;19967- 975
Link to Article
Witte  MBBarbul  A General principles of wound healing. Surg Clin North Am. 1997;77509- 528
Link to Article
Williams  RSRossi  AMChegini  NSchultz  G Effect of transforming growth factor beta on postoperative adhesion formation and intact peritoneum. J Surg Res. 1992;5265- 70
Link to Article

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