In clinical surgery, the vertical midline abdominal incision is popular but associated with healing failures. A murine model of the ventral vertical midline incision was developed in order to study the healing of this incision type.
The strength of the wild type murine ventral abdominal wall in the midline was contained within the dermis; the linea alba made a negligible contribution. Unwounded abdominal wall had a downward trend (nonsignificant) in maximal tension between 12 and 29 weeks of age. The incision attained 50% of its final strength by postoperative day 40. The maximal tension of the ventral vertical midline incision was nearly that of unwounded abdominal wall by postwounding day 60; there was no difference in unwounded vs. wounded maximal tension at postwounding day 120.
After 120 days of healing, the ventral vertical midline incision in the wild type mouse was not significantly different from age-matched nonwounded controls. About half of the final incisional strength was attained after 6 weeks of healing. The significance of this work was to establish the kinetics of wild type incisional healing in a model for which numerous genotypes and genetic tools would be available for subsequent study.
Citation: Carlson MA, Chakkalakal D (2011) Tensile Properties of the Murine Ventral Vertical Midline Incision. PLoS ONE6(9): e24212. https://doi.org/10.1371/journal.pone.0024212
Editor: Samuel J. Lin, Harvard Medical School, United States of America
Received: May 9, 2011; Accepted: August 7, 2011; Published: September 7, 2011
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: MC was supported by grants from the National Institutes of Health (K08 GM00703; www.nih.gov) and University of Nebraska Medical Center (www.unmc.edu). DC received partial salary support from Creighton University Medical Center (http://www.creightonhospital.com/en-US/Pages/default.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
The healing of skin and aponeurotic incisions has high relevance for clinical surgery, especially with regard to the kinetics of incisional strength gain and the final incisional strength attained , . In general surgery, the commonly-utilized vertical midline incision (through the linea alba) has been associated with dehiscence and hernia rates of ∼1% and 5–10%, respectively , ; decades of research (not reviewed here) has been devoted to minimizing these complications. Studies on the effects of various cytokines, genes, drugs, physical factors, etc. on incisional healing typically have focused on one or two time points early in the healing process. In contrast, there are few studies (see Discussion) which document rate of strength gain and plateau of final strength in an incisional wound, particularly in the vertical midline incision that is relevant to general surgery. In the present study, we determined the kinetics of strength gain and plateau of final strength in the ventral vertical midline incision in mice. The mouse model was chosen because numerous genotypes and genetic tools are available for this species that could be employed in future studies of incisional healing.
The microscopic anatomy of transverse sections of the wounded murine abdominal wall in the region of the linea alba is compared with that of the nonwounded animal in Figure 1 (panels B, D, F vs. A, C, E, respectively). The vertical midline incision in these transverse sections cut through the central portion of the section (heavy black arrow in Figure 1A). At this location, the abdominal wall consisted of epidermis, dermis, subcutaneous tissue, the linea alba, and peritoneum (Figure 1C). Lateral from the midline, the abdominal wall became thickened by the presence of muscular layers (rectus abdominus and panniculus carnosus; Figure 1A).
Murine ventral abdominal wall from unwounded (A, C, E) vs. wounded (B, D, F) 16 week old subjects is shown. (A&B) Transverse whole section of the ventral midline abdominal wall stained with hematoxylin and eosin. Heavy black arrow = site of vertical midline incision (red line in Figure 3A); dotted oval = site of incisional wound. Bars = 1 mm. (C&D) Low-power micrograph of abdominal wall corresponding to the above heavy black arrow and dotted oval. Bars = 100 µm. (E&F) Higher magnification of ventral midline abdominal wall at the sub-epidermal level. Bars = 10 µm. d = dermis; e = epidermis; g = gland; hf = hair follicle; la = linea alba; p = peritoneum; pc = panniculus carnosus muscle; ra = rectus abdominus muscle; sc = subcutaneous tissue.
The time elapsed between surgery and euthanasia was defined as “postwounding day” (PWD). On PWD 24, the incision was occupied by a typical wound matrix (Figure 1B, D, F) that was free of appendages such as hair follicles and glands (the one hair follicle present in Figure 1D is at the dermal margin). At higher magnification (Figure 1E, F), the cells in the wounded dermis may have been more elongate and had a higher population density compared to the cells in the nonwounded dermis, but this and other putative differences were subtle. The thickness of the abdominal wall at the site of the incision was about twice greater in the wounded vs. the unwounded subject (Table 1).
A plot of tensile force vs. elongation of a test strip (nonwounded abdominal wall in this example) is shown in Figure 2A. \ The linear relationship between the force and elongation in the elastic region is represented by the straight line superimposed on the curve. This test strip underwent irreversible plastic deformation of approximately 0.5 mm (yield-point elongation) at a yield force of ∼7.5 N (see Methods for further discussion of definitions). The test specimen then appears to undergo a change, reminiscent of “strain hardening” in metals, indicated by a small linear elastic region and a small nonlinear elastic region, each corresponding to approximately 0.5 mm elongation, before reaching the maximum tensile force of 9.6 N.
(A) Typical plot of tensile force vs. elongation in the disruption of a single test strip (blue curve) generated during tension testing of a test strip from uninjured abdominal wall loaded, at the elongation rate of 2 mm/min. The black straight line is the calculated slope of the curve in the elastic region. (B) Maximal tension sustained by tissue test strips vs. postwounding day (PWD) of the injured mouse abdominal wall compared with maximal tension vs. age of uninjured abdominal wall from age-matched control mice. Each data point represents the mean maximal tension (± SD) of 14–24 test strips. (C) Tensile stiffness vs. PWD for the same specimens as in panel B. Tensile stiffness was calculated as the slope of the straight line in Figure 2A, and is a measure of the resistance of the tissue to elongation under the applied tensile force. This is not the modulus of elasticity, since the curve in Figure 2A is not a stress vs. strain curve.
The changes in maximum tensile force sustained by the wounded abdominal wall as a function of postwounding day is compared with that of the nonwounded abdominal wall of age-matched mice in Figure 2B. The nonwounded abdominal wall specimens were tested at 12, 16, and 29 weeks of age of the mice (corresponding to PWD 0, 30, and 120 in the injured mice). The mean maximum tension of the nonwounded abdominal wall declined gradually with the age of the mouse: 9%, 7% and 11% in the three consecutive time intervals; but this trend had only marginal significance (p = 0.053, ANOVA). The decline in the mean maximum tension of the wounded abdominal wall from day 60 to 120 was 9%, which is consistent with the age-related decline of maximum tension of the nonwounded abdominal wall during the same period. On day 120, the mean maximum tension of the wounded abdominal wall was 16% less than that of the nonwounded abdominal wall, but this difference was nonsignificant (p = 0.084).
The recovery of tensile stiffness (i.e., the resistance to elongation in the elastic region of the curve in Figure 2A) of the wounded abdominal wall and the age-related decline in stiffness of the nonwounded abdominal wall (Figure 2C) have the general characteristics of the corresponding data on maximal tension (Figure 2B). The age-related decline in mean stiffness of the nonwounded abdominal wall during 12 to 29 weeks of age is approximately 40% (Figure 2C), compared with a 24% decline in mean maximal tension (Figure 2B). During this time the stiffness of the wounded abdominal wall completely recovered to the level of the nonwounded controls.
The ultimate tensile strength (UTS; see Methods) of the wounded abdominal wall on PWD 24 (0.6 MPa) was almost an order of magnitude less than that of the nonwounded tissue of age-matched controls (16 weeks), as shown in Table 1. Cross-sectional area data was available only for test strips from 16 week-old control animals and from wounded animals on PWD 24 (Table 1). Therefore, statistical comparison of UTS of wounded vs. nonwounded tissue at all time points was not possible.
1. The study of the kinetics of tensile strength in healing incisions is an essential component of experimental surgery, particularly if dealing with vascular or gastrointestinal anastomosis, tendon repair, hernia repair, and so forth. This type of experimentation has high clinical relevance, because failure of incised and sutured tissue, whether arterial wall, intestinal wall, aponeurosis, etc. has remained a vexing problem in clinical surgery , . As a soft indication of this relevance, a Google Scholar search spanning 2008–2010 using the key words “incisional healing,” “anastomosis healing” or “tendon healing” returned 16,700, 7,710, and 15,000 hits, respectively.
2. Unfortunately, research into the kinetics of tensile strength recovery in sutured wounds has to be modeled in animals, because such studies in humans are not feasible and/or ethical. Available studies of tensile strength of fascia in humans typically has been limited to study of specimens harvested from cadavers , , , , , which has made construction of a kinetic curve for human incisional healing (such as in Figure 2B) essentially impossible. So in the present study we chose to model the ventral vertical midline incision, which is well-known for its propensity to fail, as manifested acutely by dehiscence  or chronically by incisional hernia .
3. Clinically, the important mechanical property determined for each test strip in this study is the maximal tension that the test specimen can handle (see Figure 2A); this tension also is known as the “disruption force” of the specimen. If this level of tension is exceeded in a surgical wound, then wound dehiscence or incisional hernia is a likely outcome. In animal and cadaver studies of incisional wound healing , , , , , , , , , , , , , , , , , , , this disruption force (a property of the test specimen) typically is reported. The reporting of the UTS (a property of the material, irrespective of specimen size) typically has not been done in studies of tissue tensile strength. The lack of UTS reporting makes it difficult to compare results among different tensiometric studies.
4. The strength of the healing murine abdominal wall at day 120 in our study seemed to approach the strength of the age-matched uninjured abdominal wall (Figure 2B), but the strengths of both groups also appeared to be suffering from age-related decline. Previous work on the maximal force sustained by various biological tissues (including skin, bone, and tendon) in human and animal models has noted a general age-related decline in strength , , , , , , , .
5. The rapidity at which an incision gains strength and the ultimate strength that the incision attains have high clinical relevance , . A sutured incision that gains strength at relatively slow rate and/or has a relatively low final strength will be at a higher risk for failure (e.g., dehiscence or hernia) compared to an incision which gains strength more quickly and/or has a higher final strength. A convenient method to estimate rapidity of strength gain is the time required for an incision to gain 50% of its final strength (the “t50” value) ; in the present study this time can estimated from the plot in Figure 2B as ∼40 days.
6. Derivation of the t50 value requires enough experimental groups tested at appropriate times such that a plot shown in Figure 2B can be constructed. The results of previous studies which contain enough of this data are summarized in Table 2. These studies were identified with (1) a Google Scholar search using combinations of the following keywords: fascia, aponeurosis, linea alba, skin, dermis, incision, tensile, tensiometric, wound, disruption, strength; and (2) a manual search through the bibliographies of the papers found with Google Scholar. Given the time period that was searchable (nearly 100 years), the actual number of studies identified for Table 2 was not that large (n = 12).
7. Interestingly, values for “t50” in Table 2 were widely divergent for both skin (7–180 days) and fascia (3–30 days). Fascia was demonstrated in one direct comparative study to gain strength quicker than skin . The wide range of t50 values in Table 2 was somewhat troublesome, and is not easily explained. Possible causes for such divergent t50 values might include: species-specific differences in healing; location-specific differences in healing (i.e., dorsal skin vs. ventral skin); differences in the tensile testing methodology (these studies spanned a 40 year period); or inadequate numbers and/or time points of test groups.
8. Another observation from Table 2 is that full recovery of native strength in surgical incisions typically does not occur. Final strengths were in the range of 20–85% of the nonwounded tissue. Statistical testing of the Table 2 data was not available, however, so a firm conclusion on differences in final strength was not possible. Similar to the t50 values, the divergent final strengths are difficult to explain. Interestingly, one study of equine linea alba  demonstrated that the tensile strength of incised and sutured tissue actually exceeded that of nonwounded tissue after 24 weeks of healing (there was no statistical difference at the 8 week time point). We were not able to find corroborative studies that indicated that final strength of incised/sutured tissue could exceed that of native tissue.
9. In our study, the tensile strength of the abdominal wall was measured in the ventral vertical midline incision (i.e., through the linea alba), which is a common incision type utilized in open abdominal surgery. Our intent was to model this incision in a genetically “pliable” animal, with the intent that future studies could take advantage of the wide selection of genetically-modified mice and also the molecular tools that are available for that species. Interestingly, we found that the isolated linea alba in mice did not contribute a measurable degree of strength to the nonwounded abdominal wall. The tensile strength resided in the skin. In any event, we documented the rate of strength gain and the plateau strength for this incision in mice, and it is this data in this incision for this species which sets this study apart from previous studies.
10. The data of the present study focused on the tensile strength of skin strips of constant width and length. As mentioned above, the UTS needs to be determined in order to compare the native strength of one material with another. In our study, the UTS was ∼5 MPa for nonwounded skin, while the wounded skin at 24 days was almost an order of magnitude less (Table 1). For comparison, the UTS of spider silk is 1–2 GPa , various formulations of steel are in the range of 600–1,000 MPa , bone is ∼150 MPa , tendon is ∼50–100 MPa , and polypropylene is ∼30 MPa .
11. The relevance of the data in this report is that a commonly-utilized incision in abdominal surgery has been modeled in the mouse, which has not previously been done. This modeling should engender future study of the healing of this incision in this animal model, for which there are numerous genetic variants and related tools available for research use. Improvement and optimization of midline incisional healing would be relevant to open abdominal surgery, because (1) the need for open abdominal surgery will not go away in the near future ; (2) the midline incision frequently is used during open abdominal surgery ; and (3) the midline incision has a well-documented incidence of failure .
12. In summary, the strength of the murine ventral vertical midline incision at postoperative day 120 was not statistically different from nonwounded abdominal; ∼50% of final incisional strength was present at 6 weeks. These findings should have implications for future studies of the effect of various interventions on incisional healing, in that evaluation of tensile strength at an early time point (e.g., 7 or 14 days, as typically has been done) may have limited clinical relevance, because relatively little tensile strength returns in the first two weeks. If an investigator desires to evaluate an interventional effect on tensile strength at a single time point then, based on our data, the experiment may be more relevant if the investigator chooses 6 weeks as the time point, since differences in effect should be easier to discriminate at this interval.
Materials and Methods
The use of mice was approved by the Institutional Animal Care and Utilization Committee (IACUC) of the Omaha Veterans Affairs Medical Center (approval ID number 00308).
C57BL/6J mice (male, 12 weeks old at time of wounding) were anesthetized with inhalational isoflurane. Hair on the ventral abdomen was clipped, followed by depilation with a calcium hydroxide agent (Nair®); and the skin then was scrubbed with a soap solution containing 0.5% triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol; CV Medicated Lotion Soap, Steris Corp.) A 2.0 cm full-thickness abdominal wall incision (exposing the viscera) was made in the ventral midline (i.e., through the linea alba), beginning just below the xiphoid process and extending inferiorly. The incision was immediately closed using a running 7-0 polypropylene suture (Prolene, Ethicon) with 3.5× loupe magnification, taking all layers of the abdominal wall (epidermis to peritoneum). The stitch interval was 1 mm, and the bite size was 1 mm; therefore, each incision contained ∼20 suture loops. No dressing was applied, and no antibiotics were used.
Preparation of Tension Test Specimens
On the tensile testing day, each animal underwent AMVA-approved CO2 euthanasia . All suture material was removed. The anterior abdominal wall was excised with all layers from the costal margins superiorly, out to both extreme flanks laterally, and down to the hindquarters inferiorly (Figure 3A). This specimen contained the linea alba, which bisected the specimen in the vertical direction (red line in Figure 3A). A 20 mm by 10 mm rectangle of abdominal wall was excised from the central portion of this specimen (Figure 3A), and then cut into two test strips, each 20 mm by 5 mm (Figure 3B). The site of incision was positioned in the middle of the test strip during subsequent tensile testing (Figure 3C). The test strips of each subject were inked to discriminate the superior from inferior strip. The strips then were placed in phosphate-buffered saline (PBS) until testing, which was always done within 1 hr of euthanasia.
(A) Ventral image of supine subject after harvest of ventral abdominal wall; note exposure of abdominal viscera. Excised specimen is shown to the left in its approximate anatomic position. Dashed lines demonstrate how test strips were cut from the specimen. Vertical red line shows location of vertical midline incision (scale = cm). (B) Test strips cut from abdominal wall specimen similar to that shown in panel A; orientation is same as that shown in panel A (scale = cm). (C) Disruption of a test strip in the tension tester. This specimen is nearly in two halves, connected by two fine strands of tissue.
Tension Testing: Definitions
We used a standard tension testing procedure  to generate a curve of tensile force vs. elongation (Figure 2A), and to determine the yield force, maximum tensile force, and the stiffness of wounded vs. unwounded skin strips. In this report, “tension” and “tensile force” are used interchangeably.
The initial part of the curve in Figure 2A was a small nonlinear region usually observed in tensile testing of soft tissue specimens, which is devoid of meaningful data. This was followed by the elastic (i.e. linear) region that culminates at the yield point, at which plastic deformation occurred (that is, an increase in elongation without an increase in force). For soft tissue specimens such as a skin strip, the yield point usually occurs before the peak force is reached.
The tension at the yield point was defined as the yield force, and was 7.5 N in Figure 2A. The peak force, or maximum tensile force, that the strip withstood in Figure 2A was 9.6 N. If the composition of the test material is homogeneous, then the ultimate tensile strength (UTS) of the material (or simply “tensile strength”) is defined as the ratio of the peak force to the cross-sectional area of the specimen at test initiation. The typical unit of UTS is the pascal (1 Pa = 1 N/m2).
In this report, the strip composition was assumed to be homogeneous for the determination of the UTS. The UTS is an intrinsic property of the material, and is determined both by material composition and test conditions. The UTS should not be influenced by the size of the test sample.
The peak force (measured in newtons) is related, but technically not the same, as the UTS (measured in pascals); but since care was utilized in this study to maintain a reasonably constant strip size, we employed peak force as a “surrogate” or approximation for UTS in the plots of Figure 2 and in the discussion of wound kinetics.
The stiffness of the test specimen was defined as the slope of the elastic (linear) region of the force vs. elongation curve (Figure 2A) that preceded the yield point. Stiffness is a measure of the resistance of the test specimen to elongation, and is expressed in N/m.
Stiffness is related but different from the modulus of elasticity, which is defined as the slope of the stress vs. strain curve in the linear elastic region, with units of Pa. Similar to the UTS, the modulus of elasticity is an intrinsic property of the material. And analogous to the utilization of peak force as a surrogate for UTS, stiffness was used as a surrogate for the modulus of elasticity.
Tension Testing: Technique
Tension testing was performed with an Instron® Model 1011 Tester, with Series IX Instron® software, a 5 kg load cell, and 4 mm spring-loaded tissue grips (Figure 3C). Initial focus was placed on tensile testing of the linea alba, since this has been the clinically relevant layer in vertical midline incisions . It was observed, however, that the peak force recorded from isolated unwounded linea alba in the murine model was below the level of detection (<0.1 N) of the tension tester. Most, if not all, of the tensile strength of the murine abdominal wall at the ventral midline was sustained by the dermis (data not shown). Therefore, it was decided that subsequent tensile testing of the ventral midline abdominal wall would be done on all layers at this location (i.e., epidermis to peritoneum), with no attempt to isolate individual layers.
Preliminary experimentation with a variety of grip surfaces demonstrated that the least tissue slippage occurred when the grip jaws were covered with coarse-grit wet sandpaper (glued onto the jaws with cyanoacrylate). All tension tests were performed with this sandpaper-grip modification; the sandpaper was changed every ∼10 tension tests. Each test strip was loaded into the grips such that ∼5 mm of the central portion of the test strip (containing the linea alba) was exposed and centered between the superior and inferior grip at the test initiation (Figure 3). The rate of displacement was constant at 2 mm/min. The test strips were kept wet with PBS before and during the test run. The tensile force was applied to each test strip, elongating it beyond the maximal tensile force until the residual tension was less than 0.1 N, which occurred after complete or near-complete disruption of the test strip (Figure 3C).
Other preliminary tension tests revealed that excessive tissue slippage occurred within the grip jaws when the lateral musculature (i.e., the rectus and panniculus) was left intact on the test strips (data not shown). If this musculature was dissected off the test strips prior to testing, then minimal or no slippage occurred. Dissection and removal of the lateral muscles from the test strips did not disturb the integrity of the aforementioned layers at the midline. Therefore, all subsequent tension tests were performed on test strips that had the lateral musculature removed. Preliminary experimentation with the rate of displacement yielded an optimal rate of 2 mm/min. Faster rates were associated with an unacceptable decrease in experimental precision (data not shown).
Statistical analysis of the data (expressed as mean ± standard deviation) was performed using ANOVA and the two-tailed unpaired t-test with unequal variances; statistical significance was set at p<0.05.
This material was the result of work supported with resources and the use of facilities at the Omaha VA Medical Center. The authors would like to acknowledge the technical assistance of Chris Hansen, and helpful discussions with Fred Hamel, Bob Bennett, Courtney Schaffert, and Russ Alberts.
Conceived and designed the experiments: MC DC. Performed the experiments: MC. Analyzed the data: MC DC. Contributed reagents/materials/analysis tools: MC DC. Wrote the paper: MC DC.
- 1. Carlson MA (1997) Acute wound failure. Surg Clin North Am 77: 607–636.MA Carlson1997Acute wound failure.Surg Clin North Am77607636
- 2. Franz MG, Kuhn MA, Wright TE, Wachtel TL, Robson MC (2000) Perspective article: Use of the wound healing trajectory as an outcome determinant for acute wound healing. Wound Repair Regen 8: 511–516.MG FranzMA KuhnTE WrightTL WachtelMC Robson2000Perspective article: Use of the wound healing trajectory as an outcome determinant for acute wound healing.Wound Repair Regen8511516
- 3. Mudge M, Hughes LE (1985) Incisional hernia: a 10 year prospective study of incidence and attitudes. Br J Surg 72: 70–71.M. MudgeLE Hughes1985Incisional hernia: a 10 year prospective study of incidence and attitudes.Br J Surg727071
- 4. Eberl T, Jagoditsch M, Klingler A, Tschmelitsch J (2008) Risk factors for anastomotic leakage after resection for rectal cancer. Am J Surg 196: 592–598.T. EberlM. JagoditschA. KlinglerJ. Tschmelitsch2008Risk factors for anastomotic leakage after resection for rectal cancer.Am J Surg196592598
- 5. Campbell JA, Temple WJ, Frank CB, Huchcroft SA (1989) A biomechanical study of suture pullout in linea alba. Surgery 106: 888–892.JA CampbellWJ TempleCB FrankSA Huchcroft1989A biomechanical study of suture pullout in linea alba.Surgery106888892
- 6. Tera H, Aberg C (1976) Tissue strength of structures involved in musculo-aponeurotic layer sutures in laparotomy incisions. Acta Chir Scand 142: 349–355.H. TeraC. Aberg1976Tissue strength of structures involved in musculo-aponeurotic layer sutures in laparotomy incisions.Acta Chir Scand142349355
- 7. Greenall MJ, Evans M, Pollock AV (1980) Midline or transverse laparotomy? A random controlled clinical trial. Part I: Influence on healing. Br J Surg 67: 188–190.MJ GreenallM. EvansAV Pollock1980Midline or transverse laparotomy? A random controlled clinical trial. Part I: Influence on healing.Br J Surg67188190
- 8. Haxton H (1964) The influence of suture materials and methods on the healing of abdominal wounds. Br J Surg 52: 372–375.H. Haxton1964The influence of suture materials and methods on the healing of abdominal wounds.Br J Surg52372375
- 9. Leaper DJ, Pollock AV, Evans M (1977) Abdominal wound closure: a trial of nylon, polyglycolic acid and steel sutures. Br J Surg 64: 603–606.DJ LeaperAV PollockM. Evans1977Abdominal wound closure: a trial of nylon, polyglycolic acid and steel sutures.Br J Surg64603606
- 10. Carlson MA, Ludwig KA, Condon RE (1995) Ventral hernia and other complications of 1,000 midline incisions. South Med J 88: 450–453.MA CarlsonKA LudwigRE Condon1995Ventral hernia and other complications of 1,000 midline incisions.South Med J88450453
- 11. Fogdestam I (1981) A biomechanical study of healing rat skin incisions after delayed primary closure. Surg Gynecol Obstet 153: 191–199.I. Fogdestam1981A biomechanical study of healing rat skin incisions after delayed primary closure.Surg Gynecol Obstet153191199
- 12. Oxlund H, Fogdestam I, Viidik A (1979) The influence of cortisol on wound healing of the skin and distant connective tissue response. Surg Gynecol Obstet 148: 876–880.H. OxlundI. FogdestamA. Viidik1979The influence of cortisol on wound healing of the skin and distant connective tissue response.Surg Gynecol Obstet148876880
- 13. Benn SI, Whitsitt JS, Broadley KN, Nanney LB, Perkins D, et al. (1996) Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin. J Clin Invest 98: 2894–2902.SI BennJS WhitsittKN BroadleyLB NanneyD. Perkins1996Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin.J Clin Invest9828942902
- 14. Liaw L, Birk DE, Ballas CB, Whitsitt JS, Davidson JM, et al. (1998) Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 101: 1468–1478.L. LiawDE BirkCB BallasJS WhitsittJM Davidson1998Altered wound healing in mice lacking a functional osteopontin gene (spp1).J Clin Invest10114681478
- 15. Muller-Decker K, Hirschner W, Marks F, Furstenberger G (2002) The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin. J Invest Dermatol 119: 1189–1195.K. Muller-DeckerW. HirschnerF. MarksG. Furstenberger2002The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin.J Invest Dermatol11911891195
- 16. Wu N, Jansen ED, Davidson JM (2003) Comparison of mouse matrix metalloproteinase 13 expression in free-electron laser and scalpel incisions during wound healing. J Invest Dermatol 121: 926–932.N. WuED JansenJM Davidson2003Comparison of mouse matrix metalloproteinase 13 expression in free-electron laser and scalpel incisions during wound healing.J Invest Dermatol121926932
- 17. Dovi JV, He LK, DiPietro LA (2003) Accelerated wound closure in neutrophil-depleted mice. J Leukoc Biol 73: 448–455.JV DoviLK HeLA DiPietro2003Accelerated wound closure in neutrophil-depleted mice.J Leukoc Biol73448455
- 18. Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, et al. (1987) Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 237: 1333–1336.TA MustoeGF PierceA. ThomasonP. GramatesMB Sporn1987Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta.Science23713331336
- 19. Wickens JC, Whelan RL, Allendorf JD, Donahue J, Buxton E, et al. (1998) Wound tensile strength and contraction rate are not affected by laparotomy or pneumoperitoneum. Surg Endosc 12: 1166–1170.JC WickensRL WhelanJD AllendorfJ. DonahueE. Buxton1998Wound tensile strength and contraction rate are not affected by laparotomy or pneumoperitoneum.Surg Endosc1211661170
- 20. Thomay AA, Daley JM, Sabo E, Worth PJ, Shelton LJ, et al. (2009) Disruption of interleukin-1 signaling improves the quality of wound healing. Am J Pathol 174: 2129–2136.AA ThomayJM DaleyE. SaboPJ WorthLJ Shelton2009Disruption of interleukin-1 signaling improves the quality of wound healing.Am J Pathol17421292136
- 21. Lee PC, Salyapongse AN, Bragdon GA, Shears LL, Watkins SC, et al. (1999) Impaired wound healing and angiogenesis in eNOS-deficient mice. Am J Physiol 277: H1600–1608.PC LeeAN SalyapongseGA BragdonLL ShearsSC Watkins1999Impaired wound healing and angiogenesis in eNOS-deficient mice.Am J Physiol277H16001608
- 22. Levenson SM, Geever EF, Crowley LV, Oates JF 3rd, Berard CW, et al. (1965) The Healing of Rat Skin Wounds. Ann Surg 161: 293–308.SM LevensonEF GeeverLV CrowleyJF Oates 3rdCW Berard1965The Healing of Rat Skin Wounds.Ann Surg161293308
- 23. Brown GL, Curtsinger LJ, White M, Mitchell RO, Pietsch J, et al. (1988) Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann Surg 208: 788–794.GL BrownLJ CurtsingerM. WhiteRO MitchellJ. Pietsch1988Acceleration of tensile strength of incisions treated with EGF and TGF-beta.Ann Surg208788794
- 24. Mack JA, Abramson SR, Ben Y, Coffin JC, Rothrock JK, et al. (2003) Hoxb13 knockout adult skin exhibits high levels of hyaluronan and enhanced wound healing. FASEB J 17: 1352–1354.JA MackSR AbramsonY. BenJC CoffinJK Rothrock2003Hoxb13 knockout adult skin exhibits high levels of hyaluronan and enhanced wound healing.FASEB J1713521354
- 25. Muehlberger T, Moresi JM, Schwarze H, Hristopoulos G, Laenger F, et al. (2005) The effect of topical tretinoin on tissue strength and skin components in a murine incisional wound model. J Am Acad Dermatol 52: 583–588.T. MuehlbergerJM MoresiH. SchwarzeG. HristopoulosF. Laenger2005The effect of topical tretinoin on tissue strength and skin components in a murine incisional wound model.J Am Acad Dermatol52583588
- 26. Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, et al. (1997) Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136: 729–743.KG DanielsonH. BaribaultDF HolmesH. GrahamKE Kadler1997Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility.J Cell Biol136729743
- 27. Ailawadi M, Lee JM, Lee S, Hackett N, Crystal RG, et al. (2002) Adenovirus vector-mediated transfer of the vascular endothelial growth factor cDNA to healing abdominal fascia enhances vascularity and bursting strength in mice with normal and impaired wound healing. Surgery 131: 219–227.M. AilawadiJM LeeS. LeeN. HackettRG Crystal2002Adenovirus vector-mediated transfer of the vascular endothelial growth factor cDNA to healing abdominal fascia enhances vascularity and bursting strength in mice with normal and impaired wound healing.Surgery131219227
- 28. Reeves B (1968) Experiments on the tensile strength of the anterior capsular structures of the shoulder in man. J Bone Joint Surg Br 50: 858–865.B. Reeves1968Experiments on the tensile strength of the anterior capsular structures of the shoulder in man.J Bone Joint Surg Br50858865
- 29. Vogel HG (1980) Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats. Mech Ageing Dev 14: 283–292.HG Vogel1980Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats.Mech Ageing Dev14283292
- 30. Blevins FT, Hecker AT, Bigler GT, Boland AL, Hayes WC (1994) The effects of donor age and strain rate on the biomechanical properties of bone-patellar tendon-bone allografts. Am J Sports Med 22: 328–333.FT BlevinsAT HeckerGT BiglerAL BolandWC Hayes1994The effects of donor age and strain rate on the biomechanical properties of bone-patellar tendon-bone allografts.Am J Sports Med22328333
- 31. Wall JC, Chatterji SK, Jeffery JW (1979) Age-related changes in the density and tensile strength of human femoral cortical bone. Calcif Tissue Int 27: 105–108.JC WallSK ChatterjiJW Jeffery1979Age-related changes in the density and tensile strength of human femoral cortical bone.Calcif Tissue Int27105108
- 32. Kempson GE (1982) Relationship between the tensile properties of articular cartilage from the human knee and age. Ann Rheum Dis 41: 508–511.GE Kempson1982Relationship between the tensile properties of articular cartilage from the human knee and age.Ann Rheum Dis41508511
- 33. Holm-Pedersen P, Zederfeldt B (1971) Strength development of skin incisions in young and old rats. Scand J Plast Reconstr Surg 5: 7–12.P. Holm-PedersenB. Zederfeldt1971Strength development of skin incisions in young and old rats.Scand J Plast Reconstr Surg5712
- 34. Burstein AH, Reilly DT, Martens M (1976) Aging of bone tissue: mechanical properties. J Bone Joint Surg Am 58: 82–86.AH BursteinDT ReillyM. Martens1976Aging of bone tissue: mechanical properties.J Bone Joint Surg Am588286
- 35. Kempson GE (1991) Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint. Biochim Biophys Acta 1075: 223–230.GE Kempson1991Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint.Biochim Biophys Acta1075223230
- 36. Franz MG, Smith PD, Wachtel TL, Wright TE, Kuhn MA, et al. (2001) Fascial incisions heal faster than skin: a new model of abdominal wall repair. Surgery 129: 203–208.MG FranzPD SmithTL WachtelTE WrightMA Kuhn2001Fascial incisions heal faster than skin: a new model of abdominal wall repair.Surgery129203208
- 37. Chism PN, Latimer FG, Patton CS, Rohrbach BW, Blackford JT (2000) Tissue strength and wound morphology of the equine linea alba after ventral median celiotomy. Vet Surg 29: 145–151.PN ChismFG LatimerCS PattonBW RohrbachJT Blackford2000Tissue strength and wound morphology of the equine linea alba after ventral median celiotomy.Vet Surg29145151
- 38. Cunniff PM, Fossey SA, Auerbach MA, Song JW, Kaplan DL, et al. (1994) Mechanical and thermal properties of dragline silk from the spider Nephila clavipes. Polymers for Advanced Technologies 5: 401–410.PM CunniffSA FosseyMA AuerbachJW SongDL Kaplan1994Mechanical and thermal properties of dragline silk from the spider Nephila clavipes.Polymers for Advanced Technologies5401410
- 39. Cool T, Bhadeshia H, MacKay D (1997) The yield and ultimate tensile strength of steel welds. Materials Science and Engineering: A 223: 186–200.T. CoolH. BhadeshiaD. MacKay1997The yield and ultimate tensile strength of steel welds.Materials Science and Engineering: A223186200
- 40. Currey J (1998) Mechanical properties of vertebrate hard tissues. Proceedings of the Institution of Mechanical Engineers, Part H: J Engin Med 212: 399–411.J. Currey1998Mechanical properties of vertebrate hard tissues.Proceedings of the Institution of Mechanical Engineers, Part H: J Engin Med212399411
- 41. Milthorpe BK (1994) Xenografts for tendon and ligament repair. Biomaterials 15: 745–752.BK Milthorpe1994Xenografts for tendon and ligament repair.Biomaterials15745752
- 42. Fu SY, Lauke B, Mader E, Yue CY, Hu X (2000) Tensile properties of short-glass-fiber-and short-carbon-fiber-reinforced polypropylene composites. Composites Part A: Applied Science and Manufacturing 31: 1117–1125.SY FuB. LaukeE. MaderCY YueX. Hu2000Tensile properties of short-glass-fiber-and short-carbon-fiber-reinforced polypropylene composites.Composites Part A: Applied Science and Manufacturing3111171125
- 43. Delaney CP, Chang E, Senagore AJ, Broder M (2008) Clinical outcomes and resource utilization associated with laparoscopic and open colectomy using a large national database. Ann Surg 247: 819–824.CP DelaneyE. ChangAJ SenagoreM. Broder2008Clinical outcomes and resource utilization associated with laparoscopic and open colectomy using a large national database.Ann Surg247819824
- 44. Seiler CM, Deckert A, Diener MK, Knaebel HP, Weigand MA, et al. (2009) Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227). Ann Surg 249: 913–920.CM SeilerA. DeckertMK DienerHP KnaebelMA Weigand2009Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227).Ann Surg249913920
- 45. AVMA (2007) American Veterinary Medical Association Guidelines on Euthanasia. AVMA2007American Veterinary Medical Association Guidelines on Euthanasia.Online document: http://www.avma.org/issues/animal_welfare/euthanasia.pdf. Accessed January 12, 2011. Online document: http://www.avma.org/issues/animal_welfare/euthanasia.pdf. Accessed January 12, 2011.
- 46. Silver FH (1987) Biological materials: structure, mechanical properties, and modeling of soft tissues. New York University Press New York. FH Silver1987Biological materials: structure, mechanical properties, and modeling of soft tissuesNew York University Press New York
- 47. Howes EL, Sooy JW, Harvey SC (1929) The healing of wounds as determined by their tensile strength. JAMA 92: 42.EL HowesJW SooySC Harvey1929The healing of wounds as determined by their tensile strength.JAMA9242
- 48. Botsford T (1941) The tensile strength of sutured skin wounds during healing. Surg Gynecol Obstet 72: 690–697.T. Botsford1941The tensile strength of sutured skin wounds during healing.Surg Gynecol Obstet72690697
- 49. Hartzell JB, E SW (1942) The relationship of the concentration of ascorbic acid of the blood to the tensile strength of wounds in animals. Surg Gynecol Obstet 75: 1–7.JB HartzellSW E1942The relationship of the concentration of ascorbic acid of the blood to the tensile strength of wounds in animals.Surg Gynecol Obstet7517
- 50. Fast J, Nelson C, Dennis C (1947) Rate of gain in strength in sutured abdominal wall wounds. Surg Gynecol Obstet 84: 685.J. FastC. NelsonC. Dennis1947Rate of gain in strength in sutured abdominal wall wounds.Surg Gynecol Obstet84685
- 51. Nelson CA, Dennis C (1951) Wound healing; technical factors in the gain of strength in sutured abdominal wall wounds in rabbits. Surg Gynecol Obstet 93: 461.CA NelsonC. Dennis1951Wound healing; technical factors in the gain of strength in sutured abdominal wall wounds in rabbits.Surg Gynecol Obstet93461
- 52. Douglas DM (1952) The healing of aponeurotic incisions. Br J Surg 40: 79–84.DM Douglas1952The healing of aponeurotic incisions.Br J Surg407984
- 53. Adamsons RJ, Kahan SA (1970) The rate of healing of incised wounds of different tissues in rabbits. Surg Gynecol Obstet 130: 837.RJ AdamsonsSA Kahan1970The rate of healing of incised wounds of different tissues in rabbits.Surg Gynecol Obstet130837
- 54. Lichtenstein IL, Herzikoff S, Shore JM, Jiron MW, Stuart S, et al. (1970) The dynamics of wound healing. Surg Gynecol Obstet 130: 685–690.IL LichtensteinS. HerzikoffJM ShoreMW JironS. Stuart1970The dynamics of wound healing.Surg Gynecol Obstet130685690
- 55. Forrester JC, Zederfeldt BH, Hayes TL, Hunt TK (1970) Tape-closed and sutured wounds: a comparison by tensiometry and scanning electron microscopy. Br J Surg 57: 729–737.JC ForresterBH ZederfeldtTL HayesTK Hunt1970Tape-closed and sutured wounds: a comparison by tensiometry and scanning electron microscopy.Br J Surg57729737
- 56. White WL, Brody GS, Glaser AA, Marangoni RD, Beckwith TG, et al. (1971) Tensiometric studies of unwounded and wounded skin: results using a standardized testing method. Ann Surg 173: 19–25.WL WhiteGS BrodyAA GlaserRD MarangoniTG Beckwith1971Tensiometric studies of unwounded and wounded skin: results using a standardized testing method.Ann Surg1731925