Improvement of wound healing by capsaicin through suppression of the inflammatory response and amelioration of the repair process.

Wound healing is a complex biological process involving cytokines with four phases: Hemostasis, inflammation, proliferation and remodeling. Understanding the molecular mechanism of the inflammation phase could improve wound healing in the clinic as excess inflammation is a critical point for dysregulation of normal wound healing. Capsaicin (CAP), a major component of chili peppers, is known to exhibit anti­inflammatory properties through a range of different pathways, such as the neurogenic inflammation and nociception pathways. To improve the understanding of the relationship between CAP and wound healing, it is crucial to elucidate the CAP­related molecular panel involved in regulating inflammation. Therefore, the present study aimed to analyze the effects of CAP on wound healing using an in vitro cell model and an in vivo animal model. Cell migration, viability and inflammation were examined using fibroblasts, and wounds were evaluated in mice under CAP treatment. In the present study, it was found that 10 µM CAP increased cell migration and decreased interleukin 6 (IL­6) expression in in vitro cell assays. In the in vivo animal experiments, the CAP­treated wounds exhibited lower densities of polymorphonuclear neutrophils and monocytes/macrophages, as well as lower IL­6 and C­X­C motif chemokine ligand 10 protein levels. Furthermore, in CAP­treated wounds, CD31­positive capillaries and collagen deposition at the late phase of wound healing were present at higher densities. In summary, an improvement in wound healing by CAP was shown through suppression of the inflammatory response and amelioration of the repair process. These findings suggest that CAP has potential as a natural therapeutic agent for the treatment of wound healing.

Critical Factors of Dose Distribution in Breast Cancer Tomotherapy With Metallic Port Breast Tissue Expander: Image Correction, Delivery Mode, and Volume Impact.

Objectives: Breast reconstruction helps patients enhance their body image after mastectomy. Metallic ports in tissue expanders lead to dose attenuation during radiotherapy. Tissue expander volume shifts the metallic port position, possibly causing various dose alterations. This study aimed to evaluate the impact of the MAGNA-SITETM tissue expander volume on tomotherapy. Methods: Boluses and MAGNA-SITETM were placed on a Rando phantom to simulate the tissue expander under the pectoralis major. Computed tomography simulation images were transformed through replacing the electron density of (a) metallic artifact region only (Image metallic port) and (b) metallic port and artifact regions (Image Homo). Planning was calculated using fixed-beam and helical-mode techniques. Radiation was delivered with different volumes of the tissue expander. Results: Integrated 997 dose points were calculated. Planning with Image metallic port provided a calculated dose significantly closer to a realistic dose. The percentage of doses achieving the prescribed dose was significantly higher in the helical mode. In layer 2, the 100-mL tissue expander had a significantly lower measurement dose than all other volumes. Volume 150 mL had the highest increase in the measured dose difference from the plan dose at layer 2. Volume 250 mL had the highest percentage of measurement doses passing the 5% dose difference from plan dose. The coldest dose areas were noted in layers 1 and 2, especially in the metallic port-direct image mode. The average dose reduction of the measured cold areas was 6.03 ± 1.94%. Conclusion: Dose distribution was affected by the volume of the metallic port tissue expander. Tomotherapy with proper image heterogeneity correction and helical mode can reduce the attenuation from the metallic port. A tissue expander volume of 150 to 250 mL is suitable. Patients with high risk at the chest wall should be evaluated carefully to avoid underdosing. Radiation oncologists should closely cooperate with plastic surgeons to optimize treatment for each patient.

Oil Cyst Formation after Lower Blepharoplasty with Fat Grafts.

BACKGROUND: Fat grafting is increasingly used as an adjuvant surgery to blepharoplasty to refill the volume loss of an aged face and promote cellular regeneration. Complications, such as hematoma, infection, seroma, and palpable mass, may occur. We collected the patients that underwent lower blepharoplasty combined with fat graft to evaluate the incidence of oil cyst formation in the lower eyelid and to identify risk factors. MATERIAL AND METHODS: A retrospective review was performed of all patients who underwent lower or total blepharoplasty combined with fat graft at the authors' institution between January 2018 and June 2020. Complication rates were observed, and associations between preoperative variables and outcomes were assessed. RESULTS: A total of 119 patients were included in the series (all bilateral, 238 eyelids). The average patient age was 54.88 ± 11.94 years, and the average grafted fat was 1.88 ± 1.0 mL. On a per-eyelid basis for all patients, the complication rate of oil cyst formation was 6.72% (16 of 238 eyelids). The occurrence of oil cyst formation was associated with hypertension (P = 0.012; adjusted odds ratio, 9.27; 95% confidence interval, 1.62-52.99) and diabetes mellitus (P = 0.005; adjusted odds ratio, 14.02; 95% confidence interval, 2.22-88.45), but not associated with anticoagulants use (P = 0.931), age (P = 0.784), sex (P = 0.317), or fat volume (P = 0.215). The mean interval between the fat graft procedure and oil cyst noted was 236.5 ± 118.9 days. CONCLUSIONS: Oil cyst in lower eyelid can be defined as a palpable, firm, and persistent subcutaneous cystic lesion found postoperatively in any size during physical examination. The complication rate of oil cyst formation occurring after lower blepharoplasty with autologous fat grafting is 6.72%. Hypertension and diabetes mellitus maybe are risk factors of oil cyst formation. Steroid injection, needle capsulotomy, liposuction, and excision are safe and effective treatments. Reduce surgical trauma by diminishing anterior lamina trauma and capsulopalpebral fascia repair might decrease the complication rate of oil cyst formation.Transconjunctival lower blepharoplasty with fat graft or 2-stage surgery may be a choice to prevent oil cyst formation.

Eccentric free muscular perforator flaps in the proximal lateral leg for hand and foot reconstruction.

BACKGROUND: We aimed to introduce our modifications by using eccentrically located muscular perforators to shorten the distance between the recipient vessels and the flap pedicle for overcoming the "short pedicle" drawback of the proximal lateral leg perforator (PLLP) flap. PATIENTS AND METHODS: A retrospective review of 12 cases undergoing free PLLP flap for hand and foot regions reconstruction during 2010 and 2019. The mean age was 43.3 years. Most defects resulted from burn and trauma injuries. The dimensions of defects ranged from 8 × 1.5 cm2 to 12 × 6.5 cm2 . Muscular perforators were designed eccentrically 1-3 cm away from the central point of the flap to shorten the distance between the recipient vessels and the pedicle. The flap was designed to be 0.5-1 cm larger than the defect. RESULTS: The flap size ranged from 9 × 2 cm2 to 15 × 6 cm2 . All pedicles were long enough to ensure an appropriate anastomosis without tension. The post-operative course in all cases was uneventful. All flaps survived without complications. Primary repair of the donor sites was performed in all patients. Donor leg function was not hampered by flap harvesting. All patients were satisfied with the scar after at least 1 year of follow-up. CONCLUSION: Based on our experience, selection of the eccentric locations of the musculo-cutaneous perforators were effective methods to overcome the short pedicle length of this flap type. Using our modifications, thin PLLP flaps can be used in foot and hand reconstruction with minimal donor site morbidity and a high success rate.

Curcumin-Loaded Self-Microemulsifying Gel for Enhancing Wound Closure.

INTRODUCTION: Wound healing is a process in which damaged cutaneous tissues are repaired and is a dynamic physiological interaction involving several types of cells, tissues, and proteins. Compared with typical treatments, specifically in terms of multifunctional properties, bioactive drug-loaded wound dressing in a controlled and sustained delivery system is an advanced tool that significantly improves wound healing. Curcumin substantially enhances wound healing and prevents oxidative damage. However, the effects of this compound on improving wound healing are limited by its aqueous solubility, poor tissue absorption, and rapid metabolism. Hence, the current study aimed to investigate the therapeutic effect of curcumin-loaded self-microemulsifying gel on wound healing. METHODS: Ex vivo permeation studies of the skin of BALB/c mice were performed using a diffusion cell sampling system. The in vivo therapeutic effect was investigated with a full-thickness wound model. Two 6-mm full-thickness circular wounds were created on the back of the mice via punch biopsy. Then, they received different topical gels for 12 days to enhance wound closure. RESULTS: The curcumin-loaded self-microemulsifying gel had higher skin flux, cumulative amount, and permeability coefficient than the commercial gels. In addition, it enhanced wound healing. CONCLUSIONS: This is the first study that utilized self-microemulsifying gel loaded with curcumin as a delivery system for wound healing. However, the effect of this delivery system on wound healing or skin disease treatment should be further investigated.

Interleukin-6 from Adipose-Derived Stem Cells Promotes Tissue Repair by the Increase of Cell Proliferation and Hair Follicles in Ischemia/Reperfusion-Treated Skin Flaps.

The most common postoperative complication after reconstructive surgery is flap necrosis. Adipose-derived stem cells (ADSCs) and their secretomes are reported to mediate skin repair. This study was designed to investigate whether conditioned media from ADSCs (ADSC-CM) protects ischemia/reperfusion- (I/R-) induced injury in skin flaps by promoting cell proliferation and increasing the number of hair follicles. The mouse flap model of ischemia was ligating the long thoracic vessels for 3 h, followed by blood reperfusion. ADSC-CM was administered to the flaps, and their survival was observed on postoperative day 5. ADSC-CM treatment led to a significant increase in cell proliferation and the number of hair follicles. IL-6 levels in the lysate and CM from ADSCs were significantly higher than those from Hs68 fibroblasts. Furthermore, a strong decrease in cell proliferation and the number of hair follicles was observed after treatment with IL-6-neutralizing antibodies or si-IL-6-ADSC. In addition, ADSC transplantation increased flap repair, cell proliferation, and hair follicle number in I/R injury of IL-6-knockout mice. In conclusion, IL-6 secreted from ADSCs promotes the survival of I/R-induced flaps by increasing cell proliferation and the number of hair follicles. ADSCs represent a promising therapy for preventing skin flap necrosis following reconstructive and plastic surgery.

Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen.

Curcumin, a constituent of the turmeric plant, has antitumor, anti-inflammatory, and antioxidative effects, but its effects on wound healing are unclear. We created back wounds in 72 mice and treated them with or without topical curcumin (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 3, 5, 7, 9, and 12 days. Healing in wounds was evaluated from gross appearance, microscopically by haematoxylin and eosin staining, by immunohistochemistry for tumour necrosis factor alpha and alpha smooth muscle actin, and by polymerase chain reaction amplification of mRNA expression levels. Treatment caused fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. Curcumin increased the levels of tumour necrosis factor alpha mRNA and protein in the early phase of healing, which then decreased significantly. However, these levels remained high in controls. Levels of collagen were significantly higher in curcumin-treated wounds. Immunohistochemical staining for alpha smooth muscle actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment significantly suppressed matrix metallopeptidase-9 and stimulated alpha smooth muscle levels in tumour necrosis factor alpha-treated fibroblasts via nuclear factor kappa B signalling. Thus, topical curcumin accelerated wound healing in mice by regulating the levels of various cytokines.

Adipose-Derived Stem Cells Protect Skin Flaps against Ischemia/Reperfusion Injury via IL-6 Expression.

Flap necrosis is the most frequent postoperative complication encountered in reconstructive surgery. We elucidated whether adipose-derived stem cells (ADSCs) and their derivatives might induce neovascularization and protect skin flaps during ischemia/reperfusion (I/R) injury. Flaps were subjected to 3 hours of ischemia by ligating long thoracic vessels and then to blood reperfusion. Qtracker-labeled ADSCs, ADSCs in conditioned medium (ADSC-CM), or ADSC exosomes (ADSC-Exo) were injected into the flaps. These treatments led to significantly increased flap survival and capillary density compared with I/R on postoperative day 5. IL-6 levels in the cell lysates or in conditioned medium were significantly higher in ADSCs than in Hs68 fibroblasts. ADSC-CM and ADSC-Exo increased tube formation. This result was corroborated by a strong decrease in skin repair after adding IL-6-neutralizing antibodies or small interfering RNA for IL-6 ADSCs. ADSC transplantation also increased flap recovery in I/R injury of IL-6-knockout mice. IL-6 was secreted from ADSCs through signal transducer and activator of transcription phosphorylation, and then IL-6 stimulated angiogenesis and enhanced recovery after I/R injury by the classic signaling pathway. The mechanism of skin recovery includes the direct differentiation of ADSCs into endothelial cells and the indirect effect of IL-6 released from ADSCs. ADSC-CM and ADSC-Exo could be used as off-the-shelf products for this therapy.

Factors Influencing Postoperative Complications in Reconstructive Microsurgery for Head and Neck Cancer.

PURPOSE: The present study aimed to analyze multiple variables and to determine the factors influencing postoperative complications in reconstructive microsurgeries for head and neck cancer. MATERIALS AND METHODS: This was a retrospective review of the medical records of patients with head and neck cancer who underwent free flap reconstruction after ablation surgery at the Cathay General Hospital (Taipei, Taiwan) from January 2010 to December 2014. Clinical and surgical procedure-related factors were retrieved from a database and analyzed. Major complications included flap failure and life-threatening events. Minor complications were defined as requiring only routine wound care or conservative treatments. To evaluate group differences, the χ2 test was applied for categorical variables and the Mann-Whitney U test was used for continuous variables. RESULTS: In total, 158 patients (145 men [91.8%], 13 women [8.2%]) were included in this study. The mean age of the study population was 52.4 years (range, 34 to 84 yr). The mean body mass index (BMI) was 23.71 kg/m2. Most patients (93.7%) had a history of cigarette smoking. Some patients had diabetes (20.3%) and hypertension (31.6%). The percentage of patients who underwent radiotherapy before surgery was 19.6%. The percentage whose flap required a salvage operation was 8.9%. The success rate of the microvascular surgeries was 95.6%. The major complication rate was 6.3% and the minor complication rate was 27.8%. No surgical mortality was noted. CONCLUSION: In these patients, poor nutrition status, indicated by low BMI and low albumin level, was associated with a greater tendency to develop postoperative complications. Patients who had diabetes or who had received radiotherapy before surgery had a high risk for major complications. A large skin paddle seemed to be an influencing factor for minor complications, such as wound dehiscence and superficial loss of flaps.

Thalidomide inhibits fibronectin production in TGF-ß1-treated normal and keloid fibroblasts via inhibition of the p38/Smad3 pathway.

Keloids are characterized by the vigorously continuous production of extracellular matrix protein and aberrant cytokine activity in the dermis. There is a growing body of evidence that thalidomide, α-N-phthalimidoglutarimide, has anti-fibrotic properties. The aims were to examine possible therapeutic effects of thalidomide on fibronectin expression in transforming growth factor-ß1 (TGF-ß1)-treated normal fibroblasts (NFs) and keloid-derived fibroblasts (KFs) and the underlying mechanism of action, especially the involvement of mitogen-activated protein kinase (MAPKs) and Sma- and Mad-related family (Smads) pathways. In surgically removed human tissues, TGF-ß1 and fibronectin immunoreactivity was high in keloid tissue, but barely detectable in normal tissue. TGF-ß1 induced significant fibronectin expression in NFs and KFs and the effect was inhibited by pretreatment with thalidomide. TGF-ß1 also induced phosphorylation of MAPKs (ERK1/2, p38, and JNK) and Smad2/3 and pretreatment with PD98059 (an ERK1/2 inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor) inhibited TGF-ß1-induced fibronectin expression. Furthermore, pretreatment with thalidomide inhibited the TGF-ß1-induced phosphorylation of p38 and Smad3, but not that of ERK1/2, JNK, and Smad2. In addition, thalidomide pretreatment inhibited the TGF-ß-induced DNA binding activity of AP-1 and Smad3/4, caused fibronectin degradation by increasing the activity of matrix metalloproteinase 9, and decreased production of TGF-ß1 and fibronectin and the number of fibroblasts in an in vivo keloid model. These results show that thalidomide has an antifibrotic effect on keloid fibroblasts that is caused by suppression of TGF-ß1-induced p38 and Smad3 signaling. Our findings indicate that thalidomide may be a potential candidate drug for the treatment and prevention of keloids.

Using segmental renal artery as recipient artery for spinal reconstructive surgery.

STUDY DESIGN: Report of the use of one segmental artery from the left renal artery as inflow source for reconstructing a spine with recalcitrant osteomyelitis. OBJECTIVE: To describe one difficult case of spinal osteomyelitis and our reconstruction procedure. SUMMARY OF BACKGROUND DATA: The use of a vascularized fibular flap for spinal osteomyelitis has been reported previously, with vascular graft having a higher successful rate of bone union and overcoming poor perfusion beds. Because repeated spinal surgery may lead to severe scarring, the choice of recipient vessels may become a difficult issue. METHODS: A 49-year-old man with T12-L1 vertebral osteomyelitis experienced progressive spinal cord involvement. Because previous multiple sessions of antibiotic treatment and surgery proved unsuccessful, a 2-stage surgery was planned. Posterior lateral fusion from T9 to L3 with MOSS Miami spine system (DePuy, Spine Inc, Raynham, MA) and allogenous bone graft were performed, followed by anterior debridement and reconstruction with free vascularized fibular graft 1 week later. End-to-side vascular anastomosis was performed between the peroneal artery and the upper anterior segment artery of the left renal artery. RESULTS: After more than 50 months follow-up, the patient was able to walk smoothly without the aid of a brace, walker, or crutches. There were no complications, and the radiograph showed good bony union. Furthermore, renal function was normal. CONCLUSION: The segmental renal artery can be selected as one of the recipient vessels in spinal reconstruction surgery without detrimental effect on renal function in our case. The use of vascularized fibular flap is preferable in cases of recalcitrant spinal osteomyelitis. Staged surgery in the presence of spinal infection can offer good spinal stability and good bony union with lower infection risk.