Yur-Ren Kuo

Extracorporeal shock-wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ-induced diabetes

Extracorporeal shock‐wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio‐mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin‐induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW‐1) on day 3 (800 impulses at 0.09 mJ/mm2) postwounding; group IV included rats that underwent two sessions of ESWT (ESW‐2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW‐3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT‐treated rats, especially in the ESW‐2 and ESW‐3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro‐inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW‐2 and ESW‐3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo‐angiogenesis and tissue regeneration, and topical anti‐inflammatory response.

Extracorporeal shock wave treatment modulates skin fibroblast recruitment and leukocyte infiltration for enhancing extended skin-flap survival

Extracorporeal shock wave (ESW) treatment has a positive effect of rescuing ischemic skin flaps. This study assessed whether ESW treatment rescues the compromised flap tissue by suppressing the apoptosis of ischemic tissue and recruiting tissue remodeling. We used a random‐pattern extended dorsal–skin‐flap (10 × 3 cm) rodent model. Thirty‐six male Sprague–Dawley rats were divided into three groups. Group I, the control group, received no treatment. Group II received one session of ESW treatment (500 impulses at 0.15 mJ/mm2) immediately after surgery. Group III received two sessions of ESW treatment, immediately and the day after the surgery. Results indicated that the necrotic area in the flaps in group II was significantly smaller than that of the flaps in group I (p<0.01). Transferase dUTP‐nick end labeling (TUNEL) analysis revealed a significant decrease in the number of apoptotic cells in group II. Hydrogen peroxide (H2O2) expression in circulation blood was significantly decreased in group II on the day after ESW treatment. Immunohistochemical staining indicated that compared with no treatment, ESW treatment could substantially increase proliferating cell nuclear antigen (PCNA), endothelial nitric oxide synthase, and prolyl 4‐hydroxylase (rPH) expression, reduce CD45 expression, and suppress 8‐hydroxyguanosine (8‐OG) expression in the ischemic zone of the flap tissue. In conclusion, ESW treatment administered at an optimal dosage exerts a positive effect of rescuing ischemic extended skin flaps. The mechanisms of action of ESWs involve modulation of oxygen radicals, attenuation of leukocyte infiltration, decrease in tissue apoptosis, and recruitment of skin fibroblasts, which results in increased flap tissue survival.

Comparison of the outcomes of free jejunal flap reconstructions of pharyngoesophageal defects in hypopharyngeal cancer and corrosive injury patients

Free jejunal flap is one of the optimal choices for restoring upper digestive tract. The purpose of this study was to introduce the treatment strategies and to compare the outcomes of free jejunal flap for pharyngoesophageal reconstruction between hypopharyngeal cancer and chemical corrosive injured esophagus.

Micro-Autologous Fat Transplantation for Treating a Gummy Smile

Abstract Background A gummy smile is treated using many techniques, including botulinum toxin injection and various surgical interventions. Micro-autologous fat transplantation (MAFT) is a potentially advantageous alternative approach that has not been previously evaluated. Objectives This study sought to determine the long-term results of MAFT in patients with a gummy smile. Methods Seven patients with gummy smiles were evaluated for MAFT treatment between October 2015 and April 2017. Centrifuged purified fat was micro-transplanted into the nasolabial groove, ergotrid, and upper lip areas using the MAFT-GUN while the patients were under total intravenous anesthesia. Results The mean age of the 7 patients was 31 years (range, 23-40 years). The mean operating time for MAFT was 52 minutes (range, 40-72 minutes), and the mean volume of fat delivered to the nasolabial groove, ergotrid, and upper lip was 16.1 mL. The mean decreases of gingival display in the right canine incisor, left canine incisor, right canine, and left canine teeth were 4.9, 4.6, 3.8, and 4.4 mm, respectively. The smiles of the 7 patients showed significant improvement at an average follow-up time of 12.9 months. Conclusions Gummy smile treatment using MAFT is an effective, reliable, and relatively simple method, with high patient satisfaction and minimal risk of complications. Level of Evidence: 4

Extracorporeal shockwave therapy for treatment of keloid scars: Extracorporeal shockwave therapy for treatment of keloid scars

The purpose of this investigation was to study the effectiveness of extracorporeal shockwave therapy (ESWT) for the treatment of keloid scars, and compared the results with intralesional steroid injection. Thirty‐nine patients were randomly divided into 22 in ESWT group and 17 in steroid group. The ESWT group received 3 ESWT treatments in 6 weeks. The steroid group received three intra‐lesional triamcinolone injections in 6 weeks. The evaluations included gross morphology, functional outcome, local blood flow perfusion, biopsy for histopathological examination, and immunohistochemical analysis. Both groups showed significant improvements in appearance with less discoloration, flattening and softer consistency, and more elasticity of the lesions. There is a significant reduction in keloid height after treatment in both groups, and significant differences are noticed between two groups after treatment. The volume of keloid was decreased after treatment but there is no statistically significant difference between two groups. Both groups showed comparable functional scores, POSAS patient, and observer scales. The blood flow perfusion rates were statistically not significant between two groups before and after treatments. Histopathological findings revealed no significant difference in cell count, cell activity, and cell concentration between two groups. After ESWT, the significant decreases in collagen type I, type III, and Masson Trichrome stain were observed as compared with steroid group. However, very little changes were noticed in angiogenesis, inflammatory cytokines, proliferating and regeneration, and apoptosis, with no statistical significance noticed between two groups before and after treatment. This study revealed that ESWT showed comparable functional outcome and POSAS patient and observer scales as compared with steroid injection for keloid scars. Treatment of keloid scars with ESWT resulted in significant decreases in collagen fibers and increases in MMP‐13 enzyme.

Development for Wound Dressing Based on Blended Chitosan and Gelatin Hydrogels

Chitosan and gelatin are potential wound dressing materials. However, chitosan takes too much time to degrade and gelatin degrades too fast. As a result, chitosan and gelatin are blended to adjust their degradation rate. The degree of degradation test by means of weight loss and thermogravimetric analyzer after being incubated with lysozyme, which is a common enzyme in body fluid. Optical microscopy was used to observe the materials morphology after immersed in water. Finally, fibroblast cells were cultured with various material extracts to examine cell adhesion In Vitro. Cell adhesion tests showed there are no negative effect on cells. Therefore, there is no cell toxicity of chitosan on cells. Chitosan and gelatin can be promising wound dressing raw materials in future.

Fat grafting for resurfacing an exposed implant in lower extremity: A case report

Rationale: Although numerous reconstruction protocols have been reported for lower leg trauma, those for distal leg trauma remain few. We present the case of a woman with an implant exposure wound, who was successfully treated through fat grafting, without major flap surgery. Patient concerns: An 83-year-old woman with an exposed implant in lower extremity received reconstruction surgery once and the surgery failed. She refused additional major surgery and negative pressure wound therapy. Diagnoses: The diagnosis of a tibia and fibula shaft open fracture (type IIIA) complicated with an exposed implant was made. Interventions: The procedure was performed by deploying purified and emulsified fat with a Micro-Autologous Fat Transplantation gun. The required lipoaspirate amount was grossly estimated using a standard formula: 0.5 cc of a lipoaspirate per square centimeter of wound. We prepared the lipoaspirate simply through centrifugation followed by physical emulsification. The endpoint of fat grafting was when lipoaspirate began to flow out of the wound. The initial dressing after the procedure included the topical usage of biomycin ointment with AQUACEL Foam (ConvaTec Inc., NC, USA) coverage, which was later changed to INTRASITE gel (Smith & Nephew, London, UK) with a gauze dressing for 4 weeks. After 4 weeks, dressing components were changed to Mepilex (Mölnlycke Health Care, Gothenburg, Sweden) alone. Outcomes: The wound healed completely without requiring major flap surgery by 18 weeks after surgery. Lessons: Fat grafting is one kind of cell therapy and potentially has regenerative effects during wound healing. Fat grafting is critical in the healing processes of complicated wounds and might be considered a step in reconstruction surgery.

Dual Role of MiR-21-Mediated Signaling in HUVECs and Rat Surgical Flap under Normoxia and Hypoxia Condition

Restoring sufficient vascularity of the ischemia/hypoxia flap is always the critical issue in flap surgeries. In a previous studies microRNA-21 (miR-21) expression was upregulated after rat skin flap surgery. MiR-21 has been reported to be induced by hypoxia and the function of miR-21 involves in the process of angiogenesis. However, the precise regulatory mechanisms in miR-21-mediated pathways are still unclear. These issues were investigated via in vitro and in vivo experiments in this study. In human umbilical vein endothelial cells (HUVEC), the expression of hsa-miR-21-5p was induced after hypoxic culture and the induction of hsa-miR-21-5p was suppressed after sequential normoxic culture. Moreover, transfection of hsa-miR-21-5p mimic enhanced tube formation capacity in normoxia, but attenuated it in hypoxia. Furthermore, bioinformatic analysis suggested that SMAD7 was a predicted target of hsa-miR-21-5p. Our results demonstrated the effect of hsa-miR-21-5p was different on SMAD7 expression in normoxia and hypoxia. In rat skin flaps, blockage of miR-21-5p significantly increased angiogenesis via analysis of color laser Doppler imaging and repressed SMAD7 expression in ischemic skin tissue. Our study showed the opposite effect of miR-21-5p mediating angiogenesis in normoxia and hypoxia, providing important implications regarding the design of novel miRNA-based therapeutic strategies in flap surgeries.

Autologous Adipose-Derived Stem Cells Reduce Burn-Induced Neuropathic Pain in a Rat Model

Background: Burn scar pain is considered as neuropathic pain. The anti-inflammation and anti-neuroinflammation effects of adipose-derived stem cells (ASCs) were observed in several studies. We designed a study using a murine model involving the transplantation of autologous ASCs in rats subjected to burn injuries. The aim was to detect the anti-neuroinflammation effect of ASC transplantation and clarify the relationships between ASCs, scar pain, apoptosis and autophagy. Methods: We randomized 24 rats into 4 groups as followings: Group A and B, received saline injections and autologous transplantation of ASCs 4 weeks after sham burn, respectively; Group C and D, received saline injections and autologous transplantation 4 weeks after burn injuries. A designed behavior test was applied for pain evaluation. Skin tissues and dorsal horn of lumbar spinal cords were removed for biochemical analysis. Results: ASC transplantation significantly restored the mechanical threshold reduced by burn injury. It also attenuated local inflammation and central neuroinflammation and ameliorated apoptosis and autophagy in the spinal cord after the burn injury. Conclusion: In a rat model, autologous ASC subcutaneous transplantation in post-burn scars elicited anti-neuroinflammation effects locally and in the spinal cord that might be related to the relief of post-burn neuropathic pain and attenuated cell apoptosis. Thus, ASC transplantation post-burn scars shows the potential promising clinical benefits.