Thermal injury model in the rabbit ear with quantifiable burn progression and hypertrophic scar

Hypertrophic scar is a major clinical outcome of deep‐partial thickness to full thickness thermal burn injury. Appropriate animal models are a limitation to burn research due to the lack of, or access to, animal models which address the endpoint of hypertrophic scar. Lower species, such as rodents, heal mainly by contracture, which limits the duration of study. Higher species, such as pigs, heal more similarly to humans, but are associated with high cost, long duration for scar development, challenges in quantifying scar hypertrophy, and poor manageability. Here, we present a quantifiable deep‐partial thickness burn model in the rabbit ear. Burns were created using a dry‐heated brass rod for 10 and 20 seconds at 90 °C. At the time of eschar excision on day 3, excisional wounds were made on the contralateral ear for comparison. Burn wound progression, in which the wound size expands over time is a major distinction between excisional and thermal injuries, was quantified at 1 hour and 3 days after the injuries using calibrated photographs and histology and the size of the wounds was found to be unchanged from the initial wound size at 1 hour, but 10% in the 20 seconds burn wounds at 3 days. A quantifiable hypertrophic scar, measured by histology as the scar elevation index, was present in both 20 seconds burn wounds and excisional wounds at day 35. ImageJ measurements revealed that the 20 seconds burn wound scars were 22% larger than the excisional wound scars and the 20 seconds burn scar area measurements from histology were 26% greater than in the excisional wound scar. The ability to measure both burn progression and scar hypertrophy over a 35‐day time frame suits this model to screening early intervention burn wound therapeutics or scar treatments in a burn‐specific scar model.     

105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

建立一种兔耳增生性瘢痕的动物模型

目的　建立由动物自身产生的与人增生性瘢痕类似的增生性动物模型。方法　选用2 4只新西兰大耳白兔 ,分别在兔耳腹侧、背侧面作直径 1.5cm的全层皮肤缺损各 14 4个、72个 ,对创面愈合后形成的增生块进行组织病理学、层黏连蛋白 (LN)mRNA及整合素 β1mRNA检测等检查。结果　兔耳腹侧创面可产生类似人增生性瘢痕样的过度增生 ,其发生率为 71% ,以兔耳腹侧面中部为著 ,增生块最长持续时间超过伤口愈合后 15 0d ,而兔耳背侧面的创面增生块发生率不到3 0 % ,且增生块持续时间短 ,为 76d。切片镜下显示 ,增生块的真皮层存在大量成纤维细胞 ,与人增生性瘢痕结构类似。结论　兔耳腹侧面尤其腹侧面的中部可产生类似人增生性瘢痕样病理改变 ,可望成为研究瘢痕的动物模型。     

增生性瘢痕动物实验模型的建立与应用

目的建立由动物自身产生的增生性瘢痕实验模型.方法选用47只日本大耳白兔,在耳腹侧面制作6mm圆形全层皮肤缺损创面、1.5cm×4.5cm长方形创面以及耳背圆形创面共388个,进行组织学等多项观察.结果70%兔耳圆形创面可发生与人增生性瘢痕类似的增生块,增生块持续时间最长为150d;长方形创面增生块发生率为80%以上,持续时间已超过262d.增生块内有特征性的结节或漩涡状结构.创基注入TGF-β1、IFN-y,可以促进或抑制增生块的发生.原位杂交,查明内源性TGF-β1mRNA为强阳性表达.利用此模型证实成纤维细胞凋亡在病理性瘢痕发生、发展过程中起着重要的调控作用.结论兔耳可以产生与人增生性瘢痕类似的病理改变,可以用作瘢痕研究的实验模型.     

Skin wound healing in the first generation (F1) offspring of Yorkshire and red Duroc pigs: evidence for genetic inheritance of wound phenotype

Fibroproliferative scars in humans often demonstrate familial inheritance patterns, and genetics may contribute to healing and scarring. Genetic factors may also influence the scarring phenotype in a porcine model. Healing of full thickness excisional skin wounds in Yorkshire pigs closely resembles normal healing in humans, while identical wounds in red Duroc pigs form hypercontracted, hyperpigmented scars. The present study has evaluated the healing process in the first generation cross (F1) of red Duroc and Yorkshire pigs. Gross and histologic analysis revealed that the F1 animals exhibit an intermediate healing phenotype, with some features of each parent breed. F1 full thickness wounds were significantly hypercontracted and fibrotic, but apigmented. Analysis of mRNA expression patterns for a panel of relevant molecules (N=32) in the F1 animals revealed some similarities to each parent breed, as well as unique patterns for other molecules. Furthermore, a depth dependency to the healing response was observed at the gross, histologic, and molecular levels, with deep dermal wounds healing similar to Yorkshire wounds. These findings suggest that the genetic contribution to scar phenotype in this animal model is complex. However, the results indicate that further understanding in this model may provide insights into risk factors for hypertrophic scarring in human burn patients.     

Further similarities between cutaneous scarring in the female, red Duroc pig and human hypertrophic scarring

Knowledge of the pathophysiology of hypertrophic scarring following deep dermal injuries is minimal due to the lack of an animal model. We previously confirmed that thick scars in female, red Duroc pigs (FRDP) are similar to human hypertrophic scar. The purpose of this study was to evaluate TGFbeta1, IGF-1, decorin, and versican expression in FRDP wounds. Deep and shallow wounds on the backs of two FRDPs were studied over 5 months. Immunohistochemistry was performed for TGFbeta1, IGF-1, decorin, and versican. TGFbeta1 and IGF-1 mRNA were evaluated by in situ hybridization and RT-PCR. In shallow wounds (1) TGFbeta1 protein was not detectable and IGF-1 protein was seen at 10 days post-wounding. TGFbeta1 and IGF-1 mRNA were elevated for 30 days. (2) Decorin protein was not detected at 10th day, but returned to levels of uninjured skin. (3) Versican protein was not detectable at any time. In deep wounds, (1) TGFbeta1 and IGF-1 protein and mRNA were elevated early, (2) decorin protein was greatly reduced for the first 90 days, and (3) versican protein was present from 30 to 150 days. These findings correlate with findings reported in the literature for human hypertrophic scar and further validate the FRDP model of hypertrophic scarring.     

Genetic analysis of skin wound healing and scarring in a porcine model

Contraction is a normal part of skin wound healing and wound closure; however, excessive contraction and severe scarring concern patients and physicians alike. The present study has investigated the degree and kinetics of wound contraction in a porcine model of wound healing, to elucidate the genetic and molecular basis for abnormal skin wound healing and scarring. Healing of excisional skin wounds in juvenile female Yorkshire pigs closely resembled normal healing in humans. In contrast, identical wounds in female red Duroc pigs contracted significantly more, forming hypercontracted, hyperpigmented scars. Yorkshire x red Duroc F1 animals healed without hyperpigmentation, but with significantly greater wound contraction than observed in either parent breed. To examine the genetic transmission of the hypercontractile phenotype, all F1 animals were bred to a single Yorkshire boar, generating 20 backcross animals. All backcross animals healed with significantly less contraction than the normal Yorkshire animals. These findings suggest that the genetic contribution to scar phenotype in this animal model is complex, with a limited number of major genes controlling wound contraction, and an unknown number of minor genes that appear to modulate the impact of the major genes.     

Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.     

Effect of skin graft thickness on scar development in a porcine burn model

Animal models provide a way to investigate scar therapies in a controlled environment. It is necessary to produce uniform, reproducible scars with high anatomic and biologic similarity to human scars to better evaluate the efficacy of treatment strategies and to develop new treatments. In this study, scar development and maturation were assessed in a porcine full-thickness burn model with immediate excision and split-thickness autograft coverage. Red Duroc pigs were treated with split-thickness autografts of varying thickness: 0.026 in. (“thin”) or 0.058 in. (“thick”). Additionally, the thin skin grafts were meshed and expanded at 1:1.5 or 1:4 to evaluate the role of skin expansion in scar formation. Overall, the burn-excise-autograft model resulted in thick, raised scars. Treatment with thick split-thickness skin grafts resulted in less contraction and reduced scarring as well as improved biomechanics. Thin skin autograft expansion at a 1:4 ratio tended to result in scars that contracted more with increased scar height compared to the 1:1.5 expansion ratio. All treatment groups showed Matrix Metalloproteinase 2 (MMP2) and Transforming Growth Factor β1 (TGF-β1) expression that increased over time and peaked 4 weeks after grafting. Burns treated with thick split-thickness grafts showed decreased expression of pro-inflammatory genes 1 week after grafting, including insulin-like growth factor 1 (IGF-1) and TGF-β1, compared to wounds treated with thin split-thickness grafts. Overall, the burn-excise-autograft model using split-thickness autograft meshed and expanded to 1:1.5 or 1:4, resulted in thick, raised scars similar in appearance and structure to human hypertrophic scars. This model can be used in future studies to study burn treatment outcomes and new therapies.     

Pulsed dye laser in burn scars: Current concepts and future directions

Hypertrophic scarring after partial-thickness burns is common, resulting in raised, erythematous, pruritic, and contracted scars. Treatment of hypertrophic scars, especially on the face, is challenging and has high failure rates. Excisional treatment has morbidity and can create iatrogenic deformities. After an extensive experience over 10 years with laser therapy for the treatment of difficult scars, the pulsed dye laser (PDL) has emerged as a successful alternative to excision in patients with hypertrophic burn scars. Multiple studies have shown its ability to decrease scar erythema and thickness while significantly decreasing pruritis and improving the cosmetic appearance of the scar. The history of laser therapy and the mechanism of action and results of the PDL in burn scars will be reviewed. The PDL should become an integral part of the management of burn scarring and will significantly decrease the need for excisional surgery.     

Pulsed dye laser therapy and z-plasty for facial burn scars: the alternative to excision

Hypertrophic scarring after partial thickness facial burns is common when epithelialization takes longer than 3 weeks. Well-healed areas continue to mature unfavorably, resulting in raised, erythematous, and contracted scars. Excisional treatment of such scars has morbidity and can create iatrogenic deformities. The flashlamp-pumped, pulsed dye laser (PDL) in combination with z-plasty can be used as a successful alternative to excision in patients with facial hypertrophic burn scars. Fifty-seven patients with hypertrophic facial burn scars (mean age 12 years; range, 2-21 years) were treated with the PDL over the past 8 years. Thirty-four patients (60%) were also treated with z-plasties to relieve scar tension. There was one complication of postoperative blistering. Patients were divided into 3 groups based on time from burn to initial laser treatment. Group I (<1 year) had 11 patients and the laser diminished scar proliferation in these patients. Group II (1-4 years) included 24 patients and treatment resulted in reversal of hypertrophic scarring and elimination of erythema. Group III (>5 years) consisted of 22 patients. The PDL was effective in treating their stable and persistent erythema as long as 17 years after burn injury. No scars required excision in this cohort of 57 patients. The PDL should become an integral part of the management of facial burn scarring and will significantly decrease the need for excisional surgery.     

Prophylactic treatment of deep dermal burn scar to prevent hypertrophic scarring using the pulsed dye laser: a preliminary study

The pulsed dye laser, by selectively targeting blood vessels, has been used to treat established hypertrophic scars with good effect. This prospective clinical study aims to assess the feasibility of treating deep dermal burn wounds prophylactically before the formation of hypertrophic scars. Patients with burn wounds that took longer than 2 weeks to heal were primarily recruited. Each patient's burn area was divided into a treated area and a negative control. The area was laser treated with the pulsed dye laser (Chromos 585; SLS, Wales) twice at 6 weekly intervals. The appearance of the wound at both sites was inspected visually and scored at 6 weeks, and at 3, 6, and 9 months. Five patients with six burn sites (forearm, arm, and back) were treated. Treated areas achieved better scarring at 6 weeks ( = 0.04, paired -test) and at 3 months ( = 0.003, paired -test). The difference, however, became insignificant at 6 and 9 months. No notable side effects were seen in all patients. Prophylactic treatment of burn wounds with the pulsed dye laser is effective in hastening the resolution of scarring. In the authors' opinion, this treatment may revolutionize the traditional method of hypertrophic burn scar prevention, and should be considered early, especially for patients who are prone to hypertrophic scarring, and in areas where hypertrophic scarring are common.     

Partial thickness wound: Does mechanism of injury influence healing?

Wound healing is a complex multistep process which is temporally and spatially controlled. In partial thickness wounds, regeneration is possible from the stem cells in the edges of the wound and from the remnants of the epidermal appendages (such as hair follicles and sebaceous glands). This study examines whether the mechanism of injury influences healing of wounds of similar depth. Burn and excisional wounds were created on the back of Hampshire pigs and harvested at 7, 14, 28, 44, 57 and 70 days after injury and processed for histology and immunohistochemistry. Quantitative analysis of re-epithelialisation, inflammatory response and thickness of the scar and semi-quantitative analyses of the architecture of the resultant scar were performed and subjected to statistical analysis. Results demonstrated a higher number of neutrophils, macrophages and lymphocytes present in the burn on day 7 compared to the excisional wounds. The inflammatory profile of burn wounds was higher than that of excisional wounds for the first month after injury albeit less marked than on day 7 after injury. Re-epithelialisation was markedly advanced in excisional wounds compared to burn wounds at day 7 after injury, corresponding to the higher number of hair follicles in the underlying dermis of excisional wounds at this time point. The thickness of the neo-epidermis increased with time and at day 70 after wounding, the neo-epidermis of the burn was significantly thicker than the neo-epidermis of the excisional scar. Interestingly, following partial thickness excision of skin, there was neo-dermal reformation albeit with an altered architecture, lacking the normal basket-weave pattern of collagen. The thickness of the dermis of partial thickness excisional scar was greater than that of the adjacent unwounded skin. The neo-dermis of the burn scar was even thicker, with the collagen arranged more compactly and disorganised compared to excisional scar and normal skin. This study provides evidence that the mechanism of injury does influence wound healing and the resultant scarring.     

The therapeutic potential of a C‐X‐C chemokine receptor type 4 (CXCR‐4) antagonist on hypertrophic scarring in vivo

Effective prevention and treatment of hypertrophic scars (HTSs), a dermal form of fibrosis that frequently occurs following thermal injury to deep dermis, are unsolved significant clinical problems. Previously, we have found that stromal cell‐derived factor 1/CXCR4 signaling is up‐regulated during wound healing in burn patients and HTS tissue after thermal injury. We hypothesize that blood‐borne mononuclear cells are recruited into wound sites after burn injury through the chemokine pathway of stromal cell‐derived factor 1 and its receptor CXCR4. Deep dermal injuries to the skin are often accompanied by prolonged inflammation, which leads to chemotaxis of mononuclear cells into the wounds by chemokine signaling where fibroblast activation occurs and ultimately HTS are formed. Blocking mononuclear cell recruitment and fibroblast activation, CXCR4 antagonism is expected to reduce or minimize scar formation. In this study, the inhibitory effect of CXCR4 antagonist CTCE‐9908 on dermal fibrosis was determined in vivo using a human HTS‐like nude mouse model, in which split‐thickness human skin is transplanted into full‐thickness dorsal excisional wounds in athymic mice, where these wounds subsequently develop fibrotic scars that resemble human HTS as previously described. CTCE‐9908 significantly attenuated scar formation and contraction, reduced the accumulation of macrophages and myofibroblasts, enhanced the remodeling of collagen fibers, and down‐regulated the gene and protein expression of fibrotic growth factors in the human skin tissues. These findings support the potential therapeutic value of CXCR4 antagonist in dermal fibrosis and possibly other fibroproliferative disorders.     

A porcine deep dermal partial thickness burn model with hypertrophic scarring

We developed a reproducible model of deep dermal partial thickness burn injury in juvenile Large White pigs. The contact burn is created using water at 92 degrees C for 15s in a bottle with the bottom replaced with plastic wrap. The depth of injury was determined by a histopathologist who examined tissue sections 2 and 6 days after injury in a blinded manner. Upon creation, the circular wound area developed white eschar and a hyperaemic zone around the wound border. Animals were kept for 6 weeks or 99 days to examine the wound healing process. The wounds took between 3 and 5 weeks for complete re-epithelialisation. Most wounds developed contracted, purple, hypertrophic scars. On measurement, the thickness of the burned skin was approximately 1.8 times that of the control skin at week 6 and approximately 2.2 times thicker than control skin at 99 days after injury. We have developed various methods to assess healing wounds, including digital photographic analysis, depth of organising granulation tissue, immunohistochemistry, electron microscopy and tensiometry. Immunohistochemistry and electron microscopy showed that our porcine hypertrophic scar appears similar to human hypertrophic scarring. The development of this model allows us to test and compare different treatments on burn wounds.     

Nerve quantification in female red Duroc pig (FRDP) scar compared to human hypertrophic scar

A significant impediment to studying hypertrophic scar is the lack of an animal model. We have confirmed similarities between scarring in the female red Duroc pig (FRDP) and human hypertrophic scar and conclude that this model warrants validation. Reports have suggested that the cutaneous nervous system may play a role in hypertrophic scar development and several studies have shown nerve density in hypertrophic scar to be increased. The purpose of this study was to further validate the FRDP model of hypertrophic scar by quantifying nerves in FRDP tissue and comparing the findings to human hypertrophic scar. Wounds of varying depth were created on the backs of two FRDP and tissue samples were harvested at 10 days, 1 month and 5 months post-wounding. Human specimens were obtained from six burn patients. Immunohistochemistry was performed and digital images were captured. Color subtractive computer-assisted image analysis was used to quantify nerve density and nerve area fraction. The results demonstrate that nerve tissue is increased in FRDP scar tissue and is quite similar to that in human hypertrophic scar and to that described in the literature. These data provide additional evidence that the FRDP model may be useful for studying hypertrophic scarring.     

Effect of chymase activity on skin thickness in the Clawn miniature pig hypertrophic scarring model

Objective: The female red Duroc pig, a heavy and cumbersome animal, is routinely used as an animal model for hypertrophic scarring. Chymase, a chymotrypsin-like serine protease, plays an important role in skin fibrosis. This study aimed to create a lightweight pig hypertrophic scarring model using Clawn miniature pigs, and to investigate the role of chymase in hypertrophic scarring.

Methods: After creating four skin wounds (7.5?×?7.5?cm, depth?=?0.15?cm) in each pig, skin biopsies were performed after 15, 30, 60, 90, 120, and 150?days. Skin thickness, water content, hydroxyproline percentage, chymase activity, and transforming growth factor-beta 1 concentration were measured, and pathological analyses were performed.

Results and conclusions: Both tissue thickness and chymase activity were increased in scar tissue, peaked on day 90 after injury, and then gradually decreased. Peripheral scar tissue showed higher chymase activity than central scar tissue. Neither chymase activity nor transforming growth factor-beta 1 was detected in the surrounding normal skin, whereas central scar tissue showed a high transforming growth factor-beta 1 concentration, peaking on day 15, and decreasing to normal by day 120. We found the Clawn miniature pig to be a useful model for hypertrophic scarring. Chymase activity and skin thickness were well-correlated, suggesting that scars thicken when chymase activity is high.     

The effect of the angiogenesis inhibitor, angiostatin, on hypertrophic scarring

Introduction: Hypertrophic scarring is commonly seen by plastic surgeons in China. Since the etiology of hypertrophic scarring is still unknown, the only reliable treatment is surgical excision. To understand if angiogenesis plays an important role in the formation of hypertrophic scars, we investigated the effect of angiostatin, a potent angiogenesis inhibitor, on hypertrophic scar formation. Our hypothesis is that angiogenesis is required for increased scar formation and angiogenesis inhibition may be one of the methods that can be used to prevent the formation of hypertrophic scars. Methods: We have developed a reliable model in rabbits that results in hypertrophic scarring by creating a 6mm x 6mm full thickness skin wound on both ears. The cDNA for angiostatin is cloned into the pcDNA 3.1 mammalian expression vector. After the wounds re-epithelialized but prior to excessive scarring, the angiostatin expression vector was injected with Lipofectin 2000 once every two days. The expression of angiostatin was confirmed by RT-PCR. The scar tissue was harvested 14 days after injection and processed for histology and total protein. Histology was examined with routine stains, the amount of collagen deposition in the scar tissue was detected by proline assay, and TGF-β1 and VEGF expression was detected by western blot. Results: Compared to the control injection scar, the injection of angiostatin led to a much more normal-looking of scar in the rabbit ear. The proline assay demonstrated that the injection of the angiostatin expression vector resulted in much less collagen in the scar tissue. Western blot analysis showed there was less TGF-β1 and VEGF protein expression in the treated ear compared to the control. Conclusion: The introduction of a vector over-expression angiostatin can result in the decreased formation of hypertrophic scars in a rabbit ear model. This is corroborated by evidence of decreased collagen deposition, the primary extracellular matrix component of scars. In addition, we demonstrate the decreased expression of τηε pro-fibrosis growth factor, TGF-1, and the potent angiogenic factor, VEGF. These data suggest that angiogenesis inhibitors may have a potential role in the treatment of hypertrophic scarring.     

Incorporation of 3D stereophotogrammetry as a reliable method for assessing scar volume in standard clinical practice

Significant disfigurement and dysfunction is caused by hypertrophic scarring, a prevalent complication of burn wounds. A lack of objective tools in the assessment of scar parameters makes evaluation of scar treatment modalities difficult. 3D stereophotogrammetry, obtaining measurements from 3D photographs, represents a method to quantitate scar volume, and a 3D camera may have use in clinical practice. To validate this method, scar models were created and photographed with a 3D camera. Measurements from 3D image analysis of these scar models were compared to physical measurements of scar model volume. Reliability of 3D image analysis was assessed with both scar models and burn patient scars. Measurements of scar models by two independent observers were compared to determine inter-rater reliability, and measurements from 3D images of burn patient hypertrophic scars were compared to determine the consistency of the method between observers. The time taken for patient photography was recorded. No significant differences were found between the two methods of volume calculation (p = 0.89), and a plot of the differences showed agreement between the methods. The correlation coefficient between the two observers’ measurements of scar model volume was 0.92, and the intra-class correlation coefficient for patient scar volume was 0.998, showing good reliability. The time required to capture 3D photographs ranged from 2 to 6 min per patient, showing the potential for this tool to be efficiently incorporated into clinical practice. 3D stereophotogrammetry is a valid method to reliably measure scar volume and may be used to objectively measure efficacy of scar treatment modalities to track scar development and resolution.     

Development of a porcine incisional wound model and novel scarring scales

A major goal of wound management is to reduce scarring. Prior to evaluating novel anti-scarring therapies, we developed a porcine incisional wound model and scarring outcome measures. Forty-eight full-thickness incisions (3 cm in length) and excisional wounds (3 x 0.5 cm) were created on two animals and closed with sutures (n=24) or tissue adhesive (n=24). Scars were evaluated using two validated clinical scar scales and a novel scale developed for animals. Full-thickness biopsies were obtained at 5 and 8 weeks for determination of scar morphology using H&E and Congo red staining with and without polarized light. Scar tissue was classified based on the collagen fiber morphology and "redness" ratio, which is a measure of the relative distribution of collagen fiber in all three spatial dimensions. The clinical cosmetic scales were highly reliable, yet nondiscriminatory. The novel gross cosmetic and histomorphological scores were both highly reliable (0.75 and 0.70, respectively), yet poorly correlated with each other (0.17). The "redness" ratio and cross-sectional surface area measurements were also highly reliable (r=0.96 and 0.99, respectively) but unrelated to cosmetic outcomes. However, the "redness ratio" did correlate with the histomorphologic appearance of the scars, with poorer appearing clinical scars receiving lower ratios (ANOVA p=0.001). Significant differences in cosmetic scores were noted between excisional and incisional wounds favoring incisions (p=0.0019). We describe a novel porcine model for incisional and excisional wounds. The new clinical and histomorphologic outcomes were highly reliable yet poorly correlated. In general, incisional wounds healed with less apparent scarring than excisional wounds.