Dickkopf 2-Expressing Adenovirus Increases the Survival of Random-Pattern Flaps and Promotes Vasculogenesis in a Rat Model.

BACKGROUND: Dickkopf 2 (DKK2) has important roles in vertebrate development; it inhibits Wnt signaling-related processes, such as axial patterning, limb development, somitogenesis, and eye formation. However, DKK2 also acts as a Wnt signaling agonist. Dickkopf 2, induced during endothelial cell morphogenesis, promotes angiogenesis in cultured human endothelial cells. In this study, we explored the effect of DKK2-expressing adenovirus on random-pattern flaps using a rodent model. METHODS: A DKK2-expressing (dE1-RGD/DKK2) adenovirus was generated and 20 Sprague-Dawley rats were randomly divided into 2 groups: a DKK2 group and a control group. Each group was intradermally injected with 1 × 10 plaque-forming units of DKK2-expressing adenovirus (DKK2 group) or control virus (control group) 48 hours before and immediately before surgery. Then, random-pattern dorsal cutaneous flaps of 3 × 9 cm were elevated. Flap survival rates and cutaneous blood flow were measured over time, and immunohistochemical staining was performed 10 days after surgery to detect CD31 and vascular endothelial growth factor (VEGF). RESULTS: Immunofluorescence staining confirmed the expression of DKK2 in the DKK2 group. The flap survival rate was higher in the DKK2 group (80.0 ± 4.49%) than in the control group (57.5 ± 4.21%; P < 0.05). Blood flow to the most distal compartment was higher in the DKK2 group than the control group during the early postoperative period. Although vascular density was greater in the DKK2 group, there was no difference in the VEGF concentration between groups. CONCLUSIONS: The findings of the present study suggest that the DKK2-expressing adenovirus increases the survival of the random-pattern cutaneous flap independently of VEGF. The administration of the DKK2-expressing adenovirus into elevated skin flaps increased the number of capillaries and blood flow, thereby improving skin flap survival.

Antifibrotic Effects of High-Mobility Group Box 1 Protein Inhibitor (Glycyrrhizin) on Keloid Fibroblasts and Keloid Spheroids through Reduction of Autophagy and Induction of Apoptosis.

Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-κB, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-ß, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-ß-treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.

Scaffold Free Bone Regeneration Using Platelet-Rich Fibrin in Calvarial Defect Model.

Bone regeneration is a complex process influenced by various physiological factors. Platelet-rich plasma (PRP) contains many growth factors and has shown osteogenic effects. The PRP is usually activated before use. However, the authors showed that nonactivated PRP (nPRP) and activated PRP have comparable osteogenic effects in the previous study. Generally, a scaffold has been needed for the application of PRP in the cranial defect model. In this study, the authors aimed to compare the performance of scaffold free platelet-rich fibrin (PRF) to nPRP as an adjuvant for bone regeneration.Twenty-four New Zealand White rabbits were randomly allocated into 3 groups: control, nPRP, and PRF. A 15 × 15 mm defect was created on each rabbit's cranium. Acellular collagen sponges (Gelfoam) were placed on the defects of the control group, Gelfoam with nPRP was used for the nPRP group, and PRF membrane was directly applied for the PRF group. nPRP and PRF were obtained from each subject's peripheral blood. Sixteen weeks later, the volume of regenerated bone was measured using 3-dimensional computed tomography. The surface area was measured via autopsy, and the samples were then obtained for histological analysis.Bone regeneration in the experimental groups was significantly greater than that in the control group. There were no significant differences in the area of regeneration or histological characteristics between the nPRP and PRF groups.In the calvarial defect of the rabbits, the use of PRF and scaffolded PRP showed comparable bone regeneration effects, which suggested that PRF might be a therapeutic alternative for bone grafts.

Comparing the Effect of Nonactivated Platelet-Rich Plasma, Activated Platelet-Rich Plasma, and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration.

Although platelet-rich plasma (PRP) is widely used to enhance bone graft survival, the effect of PRP itself on bone regeneration is unclear. Because activated PRP releases many growth factors in a bolus, there are controversies regarding the effect of activation of the PRP on bone regeneration. Thus, we studied the effect of activated versus nonactivated PRP on bone regeneration and compared the effect with that of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a critical-sized cranial defect model. Forty New Zealand white rabbits were randomly divided into 4 groups. Defect sizing 15 × 15 mm(2) was created on the cranium of each rabbit, and then a collagen sponge soaked with normal saline, rhBMP-2, nonactivated PRP, or PRP activated with CaCl2 solution was immediately placed on the defect. After 16 weeks, using three-dimensional computed tomography and digital photography, the volume and new bone surface area were measured. The newly created bone was histologically analyzed. The experimental groups showed a significantly increased volume and surface area of new bone compared with the control group (P < 0.05), but no significant differences were found among the experimental groups. Histologic examination in the experimental groups showed newly created bone that had emerged in the center as well as the margin of the defect. Overall, these results indicate that PRP enhanced bony regeneration regardless of activation with an effect that was comparable to that of rhBMP-2. Thus, PRP has therapeutic effects on bone regeneration and may replace rhBMP-2, which is costly.

Effect of human adipose derived stem cells on scar formation and remodeling in a pig model: a pilot study.

BACKGROUND: Adipose-derived stem cells (ASCs) have positive effects in the wound healing process. OBJECTIVE: To clarify whether ASCs positively mitigate scar formation in the wound remodeling process. MATERIALS AND METHODS: Full-thickness skin defects were created on the dorsal skin of Yorkshire pigs. After the defects were transformed into early scars, ASCs were injected, and the same amount of phosphate buffered saline (PBS) was injected in the control group. Clinical and histologic examinations were performed. RESULTS: In the experimental group, the areas of scars were smaller than those of control groups. The color of scars was more similar to that of the surrounding normal tissue, and scar pliability was better. The number of mast cells decreased, and more-mature collagen arrangement was noted. In the early period of scar remodeling, the expression of transforming growth factor beta (TGF-ß)3 and matrix metalloproteinase 1 (MMP1) was greater in the experimental group than in control group. In the late period, the level of alpha smooth muscle actin and tissue inhibitor of metalloproteinase 1 were dramatically less, although the level of MMP1 was lower in the experimental group than in control group. CONCLUSIONS: Local injection of ASCs decreases scar size and provides better color quality and scar pliability. It decreases the activity of mast cells and inhibits the action of TGF-ß against fibroblasts and positively stimulates scar remodeling through greater expression of MMP molecules.

Initial report of extraperitoneal pedicle dissection in deep inferior epigastric perforator flap breast reconstruction using the da Vinci SP.

The deep inferior epigastric perforator (DIEP) flap has been widely used for autologous breast reconstruction after mastectomy. In the conventional surgical method, a long incision is needed at the anterior fascia of the rectus abdominis muscle to obtain sufficient pedicle length; this may increase the risk of incisional hernia. To shorten the incision, several trials have investigated the use of endoscopic/robotic devices for pedicle harvest; however, making multiple additional incisions for port insertion and operating in the intraperitoneal field were inevitable. Here, we describe the first case, in which a DIEP free flap was successfully made using the da Vinci SP model. Our findings can help surgeons perform operations in smaller fields with a single port in the extraperitoneal space. Moreover, this method is expected to lead to fewer donor-related complications and faster healing.

Determination of adipose-derived stem cell application on photo-aged fibroblasts, based on paracrine function.

BACKGROUND AIMS: Adipose-derived stem cells (ASC) are known to be able to restore injured tissue via differentiation and paracrine effects. In this study, we investigated the effect of ASC on photo-aged human dermal fibroblasts (HDF) based on paracrine function. In particular, we wanted to determine a more effective method of ASC application and the fate of the photo-aged fibroblasts. METHODS: We compared two application methods of ASC: transwell and conditioned medium culture with photo-aged fibroblasts. Proliferation rate, collagen synthesis, matrix metalloproteinase (MMP) production and expression of p16 were measured by real-time polymerase chain reaction (PCR) after culture. Flow cytometry for apoptosis assay was also conducted to determine the fate of the photo-aged fibroblasts. RESULTS: ASC induced proliferation of photo-aged HDF and type I collagen production and decreased MMP-1 production and expression of p16. In an apoptosis assay, ASC converted necrotic or late apoptotic cells to early apoptotic cells. These results were similar in both experimental groups. CONCLUSIONS: The results indicate that the paracrine effects of ASC may have a role that is as important as cell-to-cell communication between ASC and fibroblasts. We believe that conditioned medium may be a useful material for anti-aging skin therapy instead of cell therapy. Also, ASC might have an anti-aging effect on photo-aged fibroblasts even at a genetic level.

Antibiotic use in nasal bone fracture: a nationwide population-based cohort study in Korea.

BACKGROUND: Prophylactic antibiotics are commonly used in craniofacial surgeries. Despite the low risk of surgical site infection after nasal surgery, a lack of consensus regarding the use of antibiotic prophylaxis in the closed reduction of nasal bone fractures has led to inappropriate prescribing patterns. Through this study, we aimed to investigate the status of prophylactic antibiotic use in closed reductions of nasal bone fractures in Korea. METHODS: This retrospective cohort study was conducted using data from the National Health Insurance Service-National Sample Cohort of Korea from 2005 to 2015. We analyzed the medical records of patients who underwent closed reduction of nasal bone fractures. The sex, age, region of residence, comorbidities, and socioeconomic variables of the patients were collected from the database. Factors that affect the prescription of perioperative antibiotics were evaluated using multivariate logistic regression analysis. RESULTS: A total of 3,678 patients (mean± standard deviation of age, 28.7± 14.9 years; 2,850 men [77.5%]; 828 women [22.5%]) were included in this study. The rate of antibiotic prescription during the perioperative period was 51.4%. Approximately 68.8% of prescriptions were written for patients who had received general anesthesia. The odds of perioperative prophylactic antibiotic use were significantly higher in patients who received general anesthesia than who received local anesthesia (odds ratio, 1.59). No difference was found in terms of patient age and physician specialty. Second-generation cephalosporins were the most commonly prescribed antibiotic (45.3%), followed by third- and first-generation cephalosporins (20.3% and 18.8%, respectively). In contrast, lincomycin derivatives and aminoglycosides were not prescribed. CONCLUSION: The findings of this study showed that there was a wide variety of perioperative antibiotic prescription patterns used in nasal bone surgeries. Evidence-based guidance regarding the prescribing of antimicrobial agents for the closed reduction of nasal bone fractures should be considered in future research.

Antibiotic use in nasal bone fracture: a single-center retrospective study.

BACKGROUND: Prophylactic antibiotics are used to prevent surgical wound infection; however, proper indications must be followed with careful consideration of the risks and benefits, especially in clean or clean-contaminated wounds. Nasal bone fractures are the most common type of facial bone fracture. The most common method for treating nasal bone fracture is closed reduction, which is performed inside the nasal cavity without an incision. The purpose of this study was to determine the need for antibiotic use in the closed reduction of nasal bone fractures. METHODS: A retrospective study was conducted using data from the National Insurance Service Ilsan Hospital of the Republic of Korea between 2016 and 2018. The records of patients who underwent closed reduction of nasal bone fracture were reviewed and classified according to sex, age, comorbidities, perioperative antibiotic usage, postoperative complications, nasal packing, anesthesia type, surgeon's specialty, and operation time. RESULTS: Among the 373 patients studied, the antibiotic prescription rate was 67.3%. Just 0.8% of patients were prescribed preoperative antibiotics only, 44.0% were prescribed postoperative antibiotics only, and 22.5% were prescribed both preoperative and postoperative antibiotics. There were no cases that satisfied the definition of "surgical site infection." Furthermore, 2.1% of infection-related complications (e.g., mucosal swelling, synechia, and anosmia) occurred only in the antibiotic usage group. The use of nasal packing, anesthesia type, and surgeon's specialty did not show any difference in infection-related complication rates. CONCLUSION: According to the study findings, the routine use of perioperative antibiotics is not recommended in uncomplicated nasal bone fracture surgery.

Verrucous carcinoma arising from actinic keratosis: a case report.

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma that commonly occurs in the oral cavity. However, VC of the facial skin is relatively rare. We report a case of a 91-year-old woman with VC of the facial skin in the left zygoma area. She was diagnosed with actinic keratosis (4 × 3 cm) of the same site approximately 12 years previously, but declined further treatment. The mass was excised with a minimum of 0.4 cm from gross margins with the result of free from tumor of all margins by frozen section, allowing for primary closure after skin undermining. Basal resection was performed in the preplatysmal plane. The diagnosis of VC was confirmed by histopathological examination. Postoperatively, the wound healed without incident and with no signs of facial nerve injury. To our knowledge, this is the first reported case of VC of facial skin arising from actinic keratosis.

Primary extracranial meningioma presenting as a forehead mass.

Meningioma originates from arachnoid cap cells and is the second most common intracranial tumor; however, it can also be found in an extracranial location. A very rare primary extracranial meningioma without the presence of an intracranial component has also been reported. Primary extracranial meningiomas have been found in the skin, scalp, middle ear, and nasal cavity. A computerized tomography or magnetic resonance imaging scan is necessary to determine the presence or absence of an intracranial meningioma, and a biopsy is essential for diagnosis. We report a case of primary extracranial meningioma located in the forehead skin of a 51-year-old male.

Effects of Human Adipose-Derived Stem Cells on the Survival of Rabbit Ear Composite Grafts.

BACKGROUND: Composite grafts are frequently used for facial reconstruction. However, the unpredictability of the results and difficulties with large defects are disadvantages. Adipose-derived stem cells (ADSCs) express several cytokines, and increase the survival of random flaps and fat grafts owing to their angiogenic potential. METHODS: This study investigated composite graft survival after ADSC injection. Circular chondrocutaneous composite tissues, 2 cm in diameter, from 15 New Zealand white rabbits were used. Thirty ears were randomly divided into 3 groups. In the experimental groups (1 and 2), ADSCs were subcutaneously injected 7 days and immediately before the operation, respectively. Similarly, phosphate-buffered saline was injected in the control group just before surgery in the same manner as in group 2. In all groups, chondrocutaneous composite tissue was elevated, rotated 90 degrees, and repaired in its original position. Skin flow was assessed using laser Doppler 1, 3, 6, 9, and 12 days after surgery. At 1 and 12 days after surgery, the viable area was assessed using digital photography; the rabbits were euthanized, and immunohistochemical staining for CD31 was performed to assess neovascularization. RESULTS: The survival of composite grafts increased significantly with the injection of ADSCs (P<0.05). ADSC injection significantly improved neovascularization based on anti-CD31 immunohistochemical analysis and vascular endothelial growth factor expression (P<0.05) in both group 1 and group 2 compared to the control group. No statistically significant differences in graft survival, anti-CD31 neovascularization, or microcirculation were found between groups 1 and 2. CONCLUSIONS: Treatment with ADSCs improved the composite graft survival, as confirmed by the survival area and histological evaluation. The differences according to the injection timing were not significant.

Hepatocyte growth factor-expressing adenovirus upregulates matrix metalloproteinase-1 expression in keloid fibroblasts.

BACKGROUND: Keloids are marked by an overabundance of extracellular matrix. The antifibrotic effect of hepatocyte growth factor (HGF) is achieved by increasing the expression of matrix metalloproteinases (MMPs) that drive extracellular matrix catabolism. As such, we cultivated an RGD-modified HGF-expressing adenovirus (dE1-RGD/lacZ/HGF) for introduction into keloid fibroblasts (KFs), looking at the subsequent impact on MMP-1 expression. METHODS: KFs infected with either test virus as experimental group (dE1-RGD/lacZ/HGF) or its counterpart (dE1-RGD/lacZ) as control group were examined for HGF protein expression using an enzyme-linked immunosorbent assay (ELISA). Collagen (types I and III) and MMP-1 mRNA levels were also determined by reverse transcriptase-polymerase chain reaction, and ELISA was used to monitor MMP-1 protein expression. RESULTS: In KFs harboring the test virus, high levels of HGF were induced at a multiplicity of infection ratio of 50 (3260.6 ± 162.7 pg/ml) after 72 hours of incubation. Furthermore, reverse transcriptase-polymerase chain reaction and ELISA confirmed that MMP-1 mRNA and protein expression rose significantly in KFs after transduction by the test virus (P < 0.05). However, mRNA levels of collagen were unaffected by the experimental group. CONCLUSION: These results suggest that an HGF-expressing adenovirus may be therapeutic for keloids by increasing MMP-1 expression.

Pretarsal Augmented Lower Blepharoplasty.

BACKGROUND: Narrow and chubby pretarsal fullness is a characteristic of attractiveness and youthfulness, and pretarsal augmentation has gained popularity in Asia. Conventional lower blepharoplasty has focused on correcting the aged appearance of the lower eyelids by repositioning fat and removing excess skin. However, this technique can create flat lower eyelids and provide an indication that cosmetic surgery was performed. Therefore, our pretarsal augmented lower blepharoplasty technique focuses on restoring pretarsal fullness and creating a three-dimensional lower eyelid-cheek complex. The authors present the results of this technique, which demonstrate that it simultaneously enhances lower eyelid support and restores pretarsal fullness. METHODS: This retrospective chart review evaluated 659 consecutive patients who underwent pretarsal augmented lower blepharoplasty between 2011 and 2014. All procedures were performed by a single surgeon (H.L.C.). The outcomes and complications were assessed by evaluating the patients' preoperative and postoperative digital photographs and medical records. RESULTS: There were no permanent major complications, such as retrobulbar hemorrhage, diplopia, or hypertrophic scarring. Chemosis occurred in 90 patients (13.7 percent), 10 patients (1.5 percent) underwent minor revision because of an undercorrected nasojugal groove or loosened orbicularis oculi muscle suspension suture, and three patients (0.46 percent) experienced mild ectropion that resolved spontaneously. Approximately 98 percent of the patients were satisfied. Our technique provided a natural and younger appearance with pretarsal fullness, rather than the flattened appearance that is associated with conventional blepharoplasty. CONCLUSIONS: Pretarsal augmented lower blepharoplasty uses simple methods to restore pretarsal fullness. This technique improves periorbital contouring, rejuvenates the pretarsal roll, and provides excellent aesthetic results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Functional Outcomes of Multiple Sural Nerve Grafts for Facial Nerve Defects after Tumor-Ablative Surgery.

BACKGROUND: Functional restoration of the facial expression is necessary after facial nerve resection to treat head and neck tumors. This study was conducted to evaluate the functional outcomes of patients who underwent facial nerve cable grafting immediately after tumor resection. METHODS: Patients who underwent cable grafting from April 2007 to August 2011 were reviewed, in which a harvested branch of the sural nerve was grafted onto each facial nerve division. Twelve patients underwent facial nerve cable grafting after radical parotidectomy, total parotidectomy, or schwannoma resection, and the functional facial expression of each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results were analyzed according to patient age, follow-up duration, and the use of postoperative radiation therapy. RESULTS: Among the 12 patients who were evaluated, the mean follow-up duration was 21.8 months, the mean age at the time of surgery was 42.8 years, and the mean facial expression score was 14.6 points, indicating moderate dysfunction. Facial expression scores were not influenced by age at the time of surgery, follow-up duration, or the use of postoperative radiation therapy. CONCLUSIONS: The results of this study indicate that facial nerve cable grafting using the sural nerve can restore facial expression. Although patients were provided with appropriate treatment, the survival rate for salivary gland cancer was poor. We conclude that immediate facial nerve reconstruction is a worthwhile procedure that improves quality of life by allowing the recovery of facial expression, even in patients who are older or may require radiation therapy.

Optimal administration routes for adipose-derived stem cells therapy in ischaemic flaps.

Improvement of flap survival represents an ongoing challenge in reconstructive surgery. The angiogenic potential of adipose-derived stem cells (ASCs) offers a promising approach to improve the viability of random pattern flaps. Recently, to maximize the therapeutic effects of ASCs, increasing focus is being placed on how to deliver the stem cells to target lesions. The purpose of the present study was to compare the effectiveness of different administration routes of ASCs to improve the viability of the random pattern skin flap. ASCs labelled with PKH26 were applied via four methods to the cranially-based random pattern skin flaps of rats: (a) intravenous injection; (b) subcutaneous injection; (c) application with collagen sponge seeding; and (d) application with fibrin glue seeding. ASCs led to a significant increase in flap viability in the subcutaneous injection group and the collagen sponge group. Cutaneous blood flow was increased in the intravenous injection, subcutaneous injection and collagen sponge groups. Capillary density in the intravenous injection group and collagen sponge group was significantly greater than in the control group (no treatment). PKH26-positive cells via the collagen sponge were distributed more densely within the flap than in other groups. This study demonstrated that the collagen sponge method delivered ASCs most effectively within the flap and increased flap vascularity. The clinical therapeutic effects of ASCs can therefore be maximized when the optimal delivery route is chosen.

The effect of platelet-rich plasma on composite graft survival.

BACKGROUND: Composite grafts are suitable for facial reconstruction because of good color matching, low donor-site morbidity, acceptable texture, and easy surgical techniques. However, their use is limited to small defects and by unpredictable survival rates. As platelet-rich plasma contains large numbers of growth factors and has been widely used for tissue regeneration, this study aimed to investigate platelet-rich plasma as an adjuvant to enhance composite graft survival. METHODS: Twenty New Zealand White rabbits were used, and chondrocutaneous composite grafts were applied to their ears. The grafts were then returned to their original positions after rotation to block the original circulation from the base of the graft. Each of the individual ears was assigned randomly into one of two groups: experimental (n=20; platelet-rich plasma group) or control (n=20; control group). The surrounding skin of the composite graft was injected with either 1.0 ml of platelet-rich plasma derived from autologous whole blood in the platelet-rich plasma group or normal saline in the control group. Graft survival, cutaneous blood flow, CD31-stained vessels, and vascular endothelial growth factor protein levels were examined. RESULTS: Twelve days after surgery, graft viability in the platelet-rich plasma group was higher than in the control group. Blood perfusion was also higher in the platelet-rich plasma group. Compared with the control group, the number of CD31 blood vessels and vascular endothelial growth factor expression levels were significantly increased in the platelet-rich plasma group. CONCLUSIONS: The authors' results suggest that platelet-rich plasma restores the perfusion of composite grafts by enhancing revascularization and may exert therapeutic effects on the survival of composite grafts.

Development of a porcine skin injury model and characterization of the dose-dependent response to high-dose radiation.

A porcine skin model was developed to characterize the dose-dependent response to high-dose radiation. The dorsal skin of a mini pig was divided into four paraspinal sections, with 11 small irradiation fields (2 cm × 2 cm) in each section, and a single fraction of 15, 30, 50 or 75 Gy was delivered to each section using a 6 MeV electron beam. A spectrophotometer measured gross skin changes, and a biopsy for each radiation dose was performed in the 1st, 2nd, 4th, 6th and 9th weeks for histology, immunostaining with anti-CD31, and western blotting with IL-6 and TGF-ß1 to determine the degree of skin damage. After a 4-week latency period, erythema and dry desquamation, moist desquamation, and ulceration appeared at 4, 6 and 9 weeks, respectively. Gross skin toxicity was more pronounced, occurred early and continued to progress with irradiation >50 Gy, whereas complete healing was observed 12 weeks after 15 Gy. Spectrophotometry showed erythema indices rapidly increased during the first 4 weeks after irradiation. The number of eosinophils began rising sharply at 4 weeks and normalized after reaching peaks at 7-8 weeks. Microvessel density showed a biphasic pattern with a transient peak at 1 week, a nadir at 4-6 weeks, and maximum recovery at 9 weeks. Increase in the levels of IL-6 and TGF-ß1 was detected soon after irradiation. Most of these parameters indicated complete healing of the skin 12 weeks after 15 Gy. Our porcine skin model provides an effective platform for studying high-dose radiation-induced skin injury, in particular histologic and molecular changes, during the early latency period.