Advantages of a High-Powered Ultrasonic Vibration Cutting Device for Orthognathic Surgeries.

This study aimed to evaluate the advantages of using a high-powered ultrasonic vibration cutting device (HP-UVCD) in orthognathic surgeries. We analyzed 22 consecutive patients who underwent Le FortⅠosteotomy and bilateral sagittal split osteotomies for cleft lip and palate. We used conventional power instruments, such as reciprocating saws and rotating burrs in the first 10 patients, and an HP-UVCD in the remaining 12 patients. Surgical time, intraoperative blood loss, and postoperative inferior alveolar nerve affection were retrospectively investigated. The surgical time in the ultrasonic group (223±12.217 min) was significantly shorter than that in the conventional group (278±11.153 min, P =0.008). The amount of intraoperative blood loss in the ultrasonic group was an average of 230±45.154 g, and that in the conventional group was an average of 343±49.463 g. Although the blood loss in the ultrasonic group was reduced compared with that in the conventional group, this difference was not statistically significant ( P =0.118). All patients in both groups recovered normal sensation by 6 months postoperatively. Our findings suggest that the HP-UVCD can be used in place of a reciprocating saw or rotating burrs in orthognathic surgeries, resulting in reduced surgical time and minimal blood loss. The use of an ultrasonic bone-cutting device may allow for a safer and less invasive orthognathic surgery.

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds.

Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell-deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.

Congenital Lateral Palatal Synechia Associated With Cleft Palate: A Case Report With Long-Term Follow-Up and Review of the Literature.

Lateral palatal synechiae are rare congenital adhesions running from the free borders of the cleft palate to the lateral parts of the tongue or the oral cavity floor, typically found in cleft palate lateral synechiae syndrome. We present a case of congenital lateral palatal synechia associated with a cleft palate that we treated and followed up for 10 years. We present the long-term prognosis. We also discuss variations in intraoral synechiae associated with cleft palate and the etiology of lateral palatal synechiae through a literature review.

Reliability of Ultrasound-Guided One-Point Fixation for Zygomaticomaxillary Complex Fractures.

This study aimed to analyze the precision and postoperative stability of ultrasound guided 1-point fixation on the zygomaticomaxillary buttress for the treatment of zygomaticomaxillary complex (ZMC) fractures. The authors analyzed 24 consecutive patients who underwent ultrasound-guided 1-point fixation for ZMC fractures without separation of the fracture at the frontal process of the zygomatic bone. The authors used titanium plates in the first 6 cases, and biodegradable plates in the remaining 18 cases. The authors obtained computed tomography images preoperatively, and again the first day after surgery (T1) and 6 months after the surgery (T2). The authors calculated vertical change (VC) and horizontal change (HC) of the zygoma on computed tomography. Precision was evaluated with T1 images. Stability was evaluated from T1 to T2, and titanium and biodegradable plates were compared. From T1 images, the mean VC and HC was 0.22° (range, 1.60°-1.08°) and 0.33° (range, 1.86°-1.03°), respectively. From T1 to T2, the mean VC and HC was 0.08° and 0.28°, respectively. Comparing the types of plates, the mean HC in the biodegradable plate group was 0.39°, which was significantly greater than that in the titanium plate group (mean -0.10°). However, as the degree of change was relatively small, this did not pose any clinical problems. Our findings suggest that ultrasound-guided 1-point fixation on the zygomaticomaxillary buttress provides accurate reduction on ZMC fractures without the separation of the frontal process of the zygomatic bone fracture. Sufficient stability was obtained, even with the use of biodegradable plates.

Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation.

Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-γKO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-γKO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-γ may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.

The Birth Prevalence of Cleft Lip and/or Cleft Palate After the 2011 Tohoku Earthquake and Tsunami.

OBJECTIVE: This study examined whether the 2011 Tohoku earthquake and tsunami affected the birth prevalence of cleft lip and/or cleft palate (CL/P) in Miyagi Prefecture, where the earthquake and tsunami caused severe damage. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at university and children's hospitals in Miyagi Prefecture. PARTICIPANTS: The annual and monthly numbers of infants born with CL/P were obtained from medical records. The affected period of birth was defined as 1 year from December 1, 2011, to November 30, 2012. The control period was 5 years from January 1, 2006, to December 31, 2010. The annual and monthly numbers of births in Miyagi Prefecture were obtained using e-Stat, which is a portal for Japanese government statistics. MAIN OUTCOME MEASURES: Main outcome measures were birth prevalence of CL/P during the control and affected periods. RESULTS: There were no significant differences between the control and affected periods in the prevalence (per 10 000 live births) of cleft lip with or without palate (13.8 vs 16.7; P = .342), isolated cleft palate (5.2 vs 3.2; P = .267), or overall CL/P (19.0 vs 19.9; P = .799). CONCLUSIONS: We did not observe that the 2011 Tohoku earthquake and tsunami affected the birth prevalence of CL/P in Miyagi Prefecture, even though it severely impacted human health in the area.

Mental Development and Surgical Prognosis of Pai Syndrome: A Case Report and Review of the Literature.

Pai syndrome is a rare congenital disorder, and there are few reports about the long-term prognosis of mental development and surgical results. Here, we report a patient with Pai syndrome who was followed up from birth up to the age of 8 years. Additionally, we review 32 articles and discuss the long-term prognosis of Pai syndrome. In our case, an intracranial lipoma grew a little, but neither epilepsy nor intellectual disabilities occurred. However, she showed attention-deficit/hyperactivity disorder. Furthermore, her nasal airway was gradually obstructed by a residual intranasal polyp.

Nasopharyngoscopic Analyses through Anterior Maxillary Distraction Osteogenesis for Adolescent Patients With Cleft Palate.

Anterior maxillary distraction osteogenesis (AMDO) is a novel technique for correcting hypoplastic maxilla by sagittal expansion of the maxilla. Recent reports suggest that AMDO does not have an effect on fragile velopharyngeal function in patients with cleft palate. Furthermore, no studies have evaluated the impact of AMDO on velopharyngeal function.We adopted AMDO to correct severe hypoplastic maxilla in adolescent patients with cleft palate and evaluated its impact on velopharyngeal space and function in 8 patients aged 12 to 21 years who underwent AMDO from 2006 to 2014. All the patients had received treatment for cleft palate; however, they still exhibited marginal velopharyngeal insufficiency. The mean activation of the distractor was 10.9 ±â€Š0.9 mm.We determined changes in velopharyngeal closure ratio and closure pattern via nasopharyngoscopy. Additionally, skeletal changes were evaluated using lateral cephalograms.The mean horizontal advancement in the cephalogram obtained 1 year after the distraction was +6.4 mm. Nasopharyngoscopic examination revealed that no deterioration of velopharyngeal gap had occurred after AMDO in all 8 patients. The velopharyngeal closure pattern changed from coronal to circular in 1 patient.Our results indicate that AMDO achieved correction of hypoplastic maxilla without deterioration in velopharyngeal gap and function. Therefore, AMDO is an effective and optimal approach for correcting hypoplastic maxilla especially in patients with fragile velopharyngeal function, such as those with cleft palate.

IL-17A promotes neutrophilic inflammation and disturbs acute wound healing in skin.

In the wound healing process, neutrophils are the first inflammatory cells to move to the wound tissues. They sterilize wounds by killing microbes, and they stimulate other immune cells to protect the host from infection. In contrast, neutrophil-derived proteases cause damage to host tissues, so neutrophils play dual opposite roles in wound healing. Interleukin-17A (IL-17A) is a proinflammatory cytokine that promotes the recruitment of these cells. The role of this cytokine in the wound healing process is not fully clarified. In the present study, therefore, we examined how defect in IL-17A production affected the wound healing in skin. IL-17A-knockout (KO) mice showed promoted wound closure, myofibroblast differentiation and collagen deposition and decreased the neutrophil accumulation compared with wild-type (WT) mice. In contrast, the administration of recombinant IL-17A led to delayed wound closure, low collagen deposition and accelerated neutrophilic accumulation. In addition, the treatment of IL-17A-administered mice with a neutrophil elastase inhibitor improved the wound repair to the same level as that of WT mice. These results indicated that IL-17A hampered the wound healing process and suggested that neutrophilic inflammation caused by IL-17A may be associated with impaired wound healing in skin.

Contribution of CARD9-mediated signalling to wound healing in skin.

The inflammatory response after skin injury involves the secretion of a variety of cytokines and growth factors that are necessary for tissue repair. Caspase recruitment domain-containing protein 9 (CARD9) is an essential signalling adaptor molecule for NF-κB activation upon triggering through C-type lectin receptors (CLRs), which are expressed in macrophages and dendritic cells. However, the role of CARD9 in inflammatory responses at the wound site has not been elucidated. In this study, we analysed the role of CARD9 in the healing process of skin wounds. Wounds were created on the backs of wild-type (WT) C57BL/6 mice and CARD9 gene-disrupted (knockout [KO]) mice. We analysed per cent wound closure, and the wound tissues were harvested for analysis of leucocyte accumulation and cytokine and chemokine expressions. CARD9KO mice exhibited significant attenuation of wound closure compared with WT mice on days 5, 7 and 10 postwounding, which was associated with decreased macrophage accumulation and reduced TNF-α, IL-1ß, CCL3 and CCL4 expressions. These results suggest that CARD9 may be involved in the wound-healing process through the regulation of macrophage-mediated inflammatory responses.

Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response.

The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (Jα18KO mice) than in wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO mice than in WT mice. Treatment with anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils.

Midfacial Changes Through Anterior Maxillary Distraction Osteogenesis in Patients With Cleft Lip and Palate.

Maxillary hypoplasia is a major issue in cleft lip and palate patients, and predictable surgical maxillary advancement is required. In the present study, the changes and stability of the maxilla and soft tissue profile achieved after the application of anterior maxillary distraction osteogenesis (AMDO) using intraoral expander in unilateral cleft lip and palate and isolated cleft palate patients were investigated by comparing to the Le Fort I osteotomy (LFI) and maxillary distraction osteogenesis (DO) with rigid external distraction (RED) system.Ten patients who underwent orthognathic treatment with AMDO were examined (AMDO group). Changes in the positions of soft and hard tissue landmarks were calculated from the lateral cephalograms taken before the distraction, at the end of the distraction, and 1 year after the surgery. They were compared with the changes in 7 other unilateral cleft lip and palate patients who underwent LFI (LFI group) and 6 others who underwent DO with RED (RED group).The mean maxillary advancement of the AMDO group was similar to that of the RED group, judged by the change of point A. During DO, the AMDO group showed less clockwise rotation of mandible compared to the RED group. The soft tissue advancement of the upper lip and nose in the AMDO group was similar to that in the RED group, which was significantly larger than that in the LFI group.Our results indicate that AMDO can be surgical option to cleft lip and palate patients with less invasive but excellent improvement in both midfacial skeletal and soft tissue similar to DO-RED.

Contribution of Invariant Natural Killer T Cells to Skin Wound Healing.

In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase.

In vitroanalysis of insoluble salt formation mechanism associated with Mg corrosion-variations depending on the diffusion environment in model tissue.

Magnesium (Mg) alloys have attracted attention as biodegradable metals, but the details of their corrosion behavior under biological environment have not been elucidated. Previous studies have suggested that diffusion through blood flow may influence Mg corrosion. Therefore, to understand the degradation behaviors of Mg, we analyzed insoluble salt precipitation associated with Mg corrosion in model tissue with different diffusion rates. A pure Mg specimen was immersed into a model tissue prepared with cell culture medium supplemented by a thickener at a different concentration (0.2%-0.5%) to form the gel. Micro-focus x-ray computed tomography of the gel was performed to observe gas cavity formation around the specimen. The insoluble salt layer formed on the specimen surface were analyzed by scanning electron microscopy with energy-dispersive x-ray spectroscopy, and Raman spectroscopy. As results, gas cavity formation was observed for all specimens. At day 7, the gas cavity volume was the highest at 0.5% thickener gel followed by 0.3% thickener gel. The insoluble salts were classified into three types based on their morphology; plate-like, granular-like, and crater-like salts. The crater-like salts were observed to cover 16.8 ± 3.9% of the specimen surface immersed in the 0.5% thickener gel, at the specimen area contacted to the gas cavity. The crater-like salts were composed by Mg hydroxide and carbonate from the deepest to the top layer. In plate-like or granular-like salts, Mg carbonate was formed in the deepest layer, but phosphates and carbonates, mainly containing calcium not Mg, were formed on the surface layer. In conclusion, the increase in the thickener concentration increased the gas cavity volume contacting to the specimen surface, resulting in the increase in precipitation of Mg hydroxide and carbonate, composing crater-like salts. Mg hydroxide and carbonate precipitation suggests the local increase in OH-concentration, which may be attributed to the decrease in diffusion rate.

Multiple Buttresses Reconstruction of Maxilla with Fibular Flap Using Computer-aided Design/Computer-aided Manufacturing after Maxillectomy.

Background: The maxilla comprises horizontal and vertical buttresses, each with specific functions, supporting various organs, such as the eyes, nose, and oral cavity. Notably, they combine to form a three-dimensional structure, which enables the buttresses to provide their inherent support strength. However, reconstructing the maxilla after maxillectomy by assembling new buttresses is challenging. We successfully reconstructed all the buttresses crucial for facial appearance and dental rehabilitation using a vascularized fibular flap. Methods: Four patients underwent maxillary buttress reconstruction with a fibular flap after total or subtotal maxillectomy. We used computer-aided design/computer-aided manufacturing digital technology to osteotomize the fibula into multiple segments and assemble them to reconstruct the maxillary buttresses. Each buttress was assembled based on a preoperative simulation. Results: All patients underwent immediate one-stage maxillary reconstruction. They had good maxillary buttress alignment and acquired good facial appearance, eye position, nasal airway, and prosthetically suitable maxillary alveolus ridge. Conclusions: The combination of computer-aided design/computer-aided manufacturing digital technology and surgical techniques has enabled novel maxillary reconstruction, providing great hope to patients experiencing facial disfigurement and loss of function after maxillectomy.

Surgical treatment of nonuremic calciphylaxis: a case report and review of literature.

Calciphylaxis is characterized by extremely painful skin ulcers and develops in patients with or without severe kidney diseases. Herein, a female patient without renal dysfunction developed calciphylaxis in the right lower extremity and underwent successful surgical debridement and split-thickness skin grafting. Nevertheless, prompt wound evaluation and proper surgical approaches are essential.

Impact of palatoplasty techniques on tympanic membrane findings and hearing prognosis in children with cleft palate.

OBJECTIVE: Children with cleft palate (CP) are at high risk of developing otitis media with effusion (OME) due to Eustachian tube (ET) dysfunction. Palatoplasty has been reported to decrease the frequency of middle ear disease and improve ET function, and although various techniques have been developed, there is no consensus on the differences in the impact of different techniques on the middle ear. The purpose of this study was to determine the differential effects of palatoplasty on middle ear function and hearing. METHODS: We performed a retrospective observational survey of pediatric patients who underwent palatoplasty for CP between June 2010 and October 2018 at Tohoku University Hospital. Cases were divided into three groups depending on the palatoplasty procedures performed: the push-back palatoplasty group, the two-flap palatoplasty group, and the Furlow double-opposing Z-plasty group. We examined the differences in clinical characteristics between patients who underwent each procedure. The primary outcome variable was tympanic membrane (TM) findings, and the secondary outcome was hearing test results. RESULTS: Children who underwent the two-flap palatoplasty had a higher tympanostomy tube (TT) insertion rate and a higher total number of TT insertions than those who underwent the Furlow double-opposing Z-plasty or the push-back palatoplasty. The TM retraction rate tended to be lower in the Furlow double-opposing Z-plasty group than in the push-back palatoplasty group or the two-flap palatoplasty group. The hearing test results at the last visit were not significantly different among the three groups. CONCLUSIONS: Children who underwent the two-flap palatoplasty had a higher rate of TT insertions, potentially increasing the risk of TM perforation. In contrast, the Furlow double-opposing Z-plasty group had a lower tendency for TM regression, possibly due to improved ET function and reduced incidence of OME. It is important to understand the advantages and disadvantages of each technique before selecting one suitable for the child's cleft and arch width. Additionally, it is important to conduct regular follow-up of TM findings and hearing test results even after palatoplasty.

Cutaneous wound healing promoted by topical administration of heat-killed Lactobacillus plantarum KB131 and possible contribution of CARD9-mediated signaling.

Optimal conditions for wound healing require a smooth transition from the early stage of inflammation to proliferation, and during this time alternatively activated (M2) macrophages play a central role. Recently, heat-killed lactic acid bacteria (LAB), such as Lactobacillus plantarum (L. plantarum) have been reported as possible modulators affecting the immune responses in wound healing. However, how signaling molecules regulate this process after the administration of heat-killed LAB remains unclear. In this study, we examined the effect of heat-killed L. plantarum KB131 (KB131) administration on wound healing and the contribution of CARD9, which is an essential signaling adaptor molecule for NF-kB activation upon triggering through C-type lectin receptors, in the effects of this bacterium. We analyzed wound closure, histological findings, and inflammatory responses. We found that administration of KB131 accelerated wound closure, re-epithelialization, granulation area, CD31-positive vessels, and α-SMA-positive myofibroblast accumulated area, as well as the local infiltration of leukocytes. In particular, M2 macrophages were increased, in parallel with CCL5 synthesis. The acceleration of wound healing responses by KB131 was canceled in CARD9-knockout mice. These results indicate that the topical administration of KB131 accelerates wound healing, accompanying increased M2 macrophages, which suggests that CARD9 may be involved in these responses.

CARD9-mediated macrophage responses and collagen fiber capsule formation caused by textured-type breast implants.

BACKGROUND: An increasing number of women are undergoing breast implantation for cosmetic purposes and for reconstructive purposes after breast excision. The surface morphology of the breast implant is one of the key factors associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response following implant insertion remains unclear, however. This study conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets. METHODS: Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9, Dectin-1, Dectin-2, or Mincle. We also analyzed the collagen fiber capsule thickness, histological findings, and macrophage inflammatory response, including TGF-ß synthesis. RESULTS: We found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-ß-expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-ß synthesis, although the responsible C-type lectin receptors (CLRs) remain to be clarified. CONCLUSIONS: These results suggest that CARD9 may have a strong impact on silicone sheet insertion through the regulation of macrophage responses.

Low-energy extracorporeal shock wave therapy enhances skin wound healing in diabetic mice: a critical role of endothelial nitric oxide synthase.

Low-energy extracorporeal shock wave (LE-ESW) treatment has been shown to accelerate wound repair; however, the mechanisms of treatment remain unclear. In the present study, we addressed the role of endothelial nitric oxide synthase (eNOS). A single LE-ESW treatment accelerated the healing of wounds in diabetic mice caused by the injection of streptozotocin. This accelerated healing was accompanied by the increased expression of eNOS and vascular endothelial growth factor (VEGF) and the generation of new vessels at the wound tissues. These results raised the possibility that eNOS may be involved in the beneficial effects of LE-ESW treatment. To address this possibility, we compared the effects of this treatment between mice with a genetic disruption of eNOS knockout (eNOS-KO mice) and wild-type (WT) control mice. Interestingly, the LE-ESW-induced acceleration of wound closure and the increase in VEGF expression and neovascularization was significantly attenuated in eNOS-KO mice compared with WT mice. Considered collectively, these results showed that eNOS was induced at the wound tissues by LE-ESW treatment and played a critical role in the therapeutic effects of this treatment by accelerating the wound healing by promoting VEGF expression and neovascularization.