Comprehensive characterization of polyproline tri-helix macrocyclic nanoscaffolds for predictive ligand positioning.

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially crossover helix ends is elucidated. This structural model aligns well with scanning tunneling microscopy (STM) imaging. The present work enhances the precision of nanoscale organic synthesis, offering prospects for controlled ligand positioning on scaffolds. This advancement paves the way for further applications in nanomedicine through selective protein interaction, manipulation of cell surface receptor functions, and developments of more complex polyproline-based nanostructures.

Dilute Povidone-Iodine Solution Soaking Is Ineffective in Improving Outcomes of Necrotizing Fasciitis Caused by Diabetic Foot.

ABSTRACT: Wound soaking is a physical debridement method that helps reduce bacterial colonization and consequently promotes wound healing. Although soaking in povidone-iodine solution was ineffective in reducing bacterial colonization in acute trauma wounds, there is still a lack of evidence supporting the efficacy of this method in treating severe soft tissue infection. This study aimed to explore the effects of wound soaking in 1% dilute povidone-iodine solution on necrotizing fasciitis caused by diabetic foot ulcers. We retrospectively reviewed and finally included 153 patients who were admitted because of diabetic foot ulcers after undergoing fasciotomy for necrotizing infection from January 2018 to December 2021. Results showed no statistical difference in the outcomes between patients in the soaking and nonsoaking groups. End-stage renal disease (P = 0.029) and high serum C-reactive protein level (P = 0.007) were the only independent factors for below-knee amputation in the univariate and multivariate logistic regression analyses. Therefore, soaking diabetic wounds with severe infection in 1% dilute povidone-iodine solution may not reduce the hospital length of stay, risk of below-knee amputation, and readmission rate.

Outcome analysis of free flap reconstruction for head and neck cancer with intraoperative indocyanine green angiography.

BACKGROUND: Intraoperative indocyanine green (ICG) angiography is used in free flap surgery to evaluate the patency of vessel anastomosis. This study evaluated the outcomes of intraoperative ICG angiography in free flap surgery for head and neck cancer. MATERIALS AND METHODS: This was a retrospective study of free flap reconstruction for head and neck cancer performed between 2015 and 2021. The outcomes analyzed were the total flap failure rate, re-exploration rate, and flap salvage rate. Differences in outcomes were compared in patients treated using intraoperative ICG angiography and those treated without. RESULTS: Of the 520 free flap surgeries in the 486 enrolled patients, 259 cases underwent intraoperative ICG angiography. In this group, there were 10 (3.9%) cases of total flap failure. In the non-ICG group, there were 22 cases (8.4%). There were 35 (13.5%) cases requiring re-exploration in the ICG group and 40 (15.3%) in the non-ICG group. The difference was not statistically significant. The flap salvage rate was 75.8% (25/33) in the ICG group and 51.4% (18/35) in the non-ICG group, which was a significant difference. CONCLUSION: We found that free flap surgery with intraoperative ICG angiography significantly decreased total flap failure rate and significantly increased salvage rate but did not significantly affect the re-exploration rate.

Total Surface Area of a Through-and-Through Oromandibular Defect Is Associated With Thromboembolic Events for Reconstruction With a Single Fibula Free Flap.

BACKGROUND: Reconstruction of through-and-through composite oromandibular defects (COMDs) has been a challenge to plastic surgeons for decades. When using a free osteoseptocutaneous fibular flap, the skin paddle is restricted by the orientation of the peroneal vessels and the inset of bone segment(s). Although the combination of double flaps for extensive COMDs is viable and reliable, the decision of single- or double-flap reconstruction is still debated, and the risk factors leading to complications and flap failure of single-flap reconstruction are less discussed. AIM AND OBJECTIVES: The aim of this study was to determine objectively predictive factors for postoperative vascular complications in through-and-through COMDs reconstructed with a single fibula flap. METHODS: This was a retrospective cohort study in patients who underwent single free fibular flap reconstruction for through-and-through COMDs in a tertiary medical center from 2011 to 2020. The enrolled patients' characteristics, surgical methods, thromboembolic event, flap outcomes, intensive care unit care, and total hospital length of stay were analyzed. RESULTS: A total of 43 consecutive patients were included in this study. Patients were categorized into a group without thromboembolic events (n = 35) and a group with thromboembolic events (n = 8). The 8 subjects with thromboembolic events were failed to be salvaged. There was no significant difference in age, body mass index, smoking, hypertension, diabetes mellitus, and history of radiotherapy. The length of bony defect (6.70 ± 1.95 vs 9.04 ± 2.96, P = 0.004) and the total surface area (105.99 ± 60.33 vs 169.38 ± 41.21, P = 0.004) were the 2 factors that showed a significant difference between the groups. Total surface area was the only significant factor in univariate logistic regression for thromboembolic event (P = 0.020; odds ratio, 1.02; 95% confidence interval [CI], 1.003-1.033) and also in multivariate logistic regression analysis after adjusting confounding factors (P = 0.033; odds ratio, 1.026; 95% CI, 1.002-1.051).The cutoff level of total surface area in determining thromboembolic event development was 159 cm2 (P = 0.005; sensitivity of 75% and specificity of 82.9%; 95% CI, 0.684-0.952). CONCLUSIONS: Free fibula flap has its advantages and drawbacks on mandible restoration. Because there is a lack of indicators before, a large total surface area may be an objective reference for single-flap reconstruction of through-and-through COMDs due to an elevated risk of thromboembolic event.

Identification of lymph vessels using an indocyanine green camera-integrated operative microscope for lymphovenous anastomosis in the treatment of secondary lymphedema.

OBJECTIVE: Lymphedema is a debilitating disease that impairs a patient's quality of life. Although lymphovenous anastomosis (LVA) can cure lymphedema, successful LVAs rely on the precise identification of the lymph vessels. In the present study, we assessed the use of a near-infrared camera-integrated operating microscope for preoperative mapping of the lymphatic vessels and evaluated the outcome of LVAs in patients with secondary lymphedema of a limb. METHODS: We retrospectively reviewed patients with secondary unilateral lymphedema who had undergone LVA surgery with the lymph vessels identified using a near-infrared camera-integrated operating microscope (Moller 3-1000; Möller-Wedel Optical GmbH, Wedel, Germany) between 2020 and 2021. The lymph vessels identified using near-infrared fluorescence lymphography, diameter of the vessels used for anastomosis, anastomosis configuration, and perioperative limb circumference were recorded. RESULTS: Overall, 35 LVAs were performed in six patients with secondary lymphedema, with a mean number of 5.8 LVAs per limb. The anastomotic configurations were end-to-end in 26 LVAs, side-to-end in 2 LVAs, and end-to-side in 7 LVAs. The diameter of the lymph vessels ranged from 0.3 to 0.9 mm (mean, 0.62 ± 0.18 mm) and that of the vein from 0.4 to 1.2 mm (mean, 0.75 ± 0.21 mm). The changes in the lymphedema index and estimated limb volume indicated a postoperative decrease in edema. CONCLUSIONS: We found a near-infrared camera-integrated operating microscope useful for the preoperative identification of functional lymph vessels. Our results have shown that microsurgical LVAs can be performed using an integrated indocyanine green camera without an independent indocyanine green detector.

Direct mapping from PET coincidence data to proton-dose and positron activity using a deep learning approach.

Objective. Obtaining the intrinsic dose distributions in particle therapy is a challenging problem that needs to be addressed by imaging algorithms to take advantage of secondary particle detectors. In this work, we investigate the utility of deep learning methods for achieving direct mapping from detector data to the intrinsic dose distribution.Approach. We performed Monte Carlo simulations using GATE/Geant4 10.4 simulation toolkits to generate a dataset using human CT phantom irradiated with high-energy protons and imaged with compact in-beam PET for realistic beam delivery in a single-fraction (∼2 Gy). We developed a neural network model based on conditional generative adversarial networks to generate dose maps conditioned on coincidence distributions in the detector. The model performance is evaluated by the mean relative error, absolute dose fraction difference, and shift in Bragg peak position.Main results. The relative deviation in the dose and range of the distributions predicted by the model from the true values for mono-energetic irradiation between 50 and 122 MeV lie within 1% and 2%, respectively. This was achieved using 105coincidences acquired five minutes after irradiation. The relative deviation in the dose and range for spread-out Bragg peak distributions were within 1% and 2.6% uncertainties, respectively.Significance. An important aspect of this study is the demonstration of a method for direct mapping from detector counts to dose domain using the low count data of compact detectors suited for practical implementation in particle therapy. Including additional prior information in the future can further expand the scope of our model and also extend its application to other areas of medical imaging.

A 2D strip ionization chamber array with high spatiotemporal resolution for proton pencil beam scanning FLASH radiotherapy.

PURPOSE: Experimental measurements of two-dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip-segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates. METHODS: A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250-MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel-plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT-XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip-type detector. RESULTS: The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20-kHz sampling rate (50 µs per event) and a linearity of R2  > 0.99 for both dose and dose rate with nozzle beam currents ranging from 1 to 215 nA. The 2D dose comparison to the film measurement resulted in a gamma passing rate of 99.8% (2 mm/2%). A measurement-based proton PBS 2D FLASH dose rate distribution was compared to simulation results and showed a gamma passing rate of 97.3% (2 mm/2%). CONCLUSIONS: The newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH-RT.

Accuracy of the Application of 3-Dimensional Printing Models in Orbital Blowout Fractures-A Preliminary Study.

BACKGROUND: Application of 3-dimensional (3D) printing technology has grown in the medical field over the past 2 decades. In managing orbital blowout fractures, 3D printed models can be used as intraoperative navigators and could shorten the operational time by facilitating prebending or shaping of the mesh preoperatively. However, a comparison of the accuracy of computed tomography (CT) images and printed 3D models is lacking. MATERIAL AND METHODS: This is a single-center retrospective study. Patients with unilateral orbital blowout fracture and signed up for customized 3D printing model were included. Reference points for the 2D distance were defined (intersupraorbital notch distance, transverse horizontal, sagittal vertical, and anteroposterior axes for orbital cavity) and measured directly on 3D printing models and on corresponding CT images. The difference and correlation analysis were conducted. RESULTS: In total, 9 patients were reviewed from June 2017 to December 2020. The mean difference in the intersupraorbital notch measurement between the 2 modules was -0.14 mm (P = 0.67). The mean difference in the distance measured from the modules in the horizontal, vertical, and anteroposterior axes of the traumatic orbits was 0.06 mm (P = 0.85), -0.23 mm (P = 0.47), and 0.51 mm (P = 0.32), whereas that of the unaffected orbits was 0.16 mm (P = 0.44), 0.34 mm (P = 0.24), and 0.1 mm (P = 0.88), respectively. Although 2D parameter differences (<1 mm) between 3D printing models and CT images were discovered, they were not statistically significant. CONCLUSIONS: Three-dimensional printing models showed high identity and correlation to CT image. Therefore, personalized models might be a reliable tool of virtual surgery or as a guide in realistic surgical scenarios for orbital blowout fractures.

Postoperative Sedation Duration as an Independent Risk Factor for Postoperative Pneumonia in Head and Neck Cancer Patients Undergoing Free Flap Reconstruction.

OBJECTIVE: Patients who had reconstruction for head and neck cancer usually have long duration of postoperative sedation and intensive care. This is due to the complex nature of large-area soft tissue defect surgeries and upper respiratory tract infections associated with them. Postoperative pulmonary complications are common in these patients. In this study, we analyzed the risk factors and the relationship between postoperative complications and the duration of sedation to improve the patients' recovery process after free flap reconstruction for head and neck surgery. MATERIALS AND METHODS: This was a retrospective study that included 188 patients who had head and neck surgery with free flap reconstruction in 2011 (traditional recovery group) and 2018 (early recovery group). Postoperative recovery events were compared between the 2 groups. Complications such as pneumonia, wound infection, vascular thrombosis, and bleeding were also analyzed. RESULTS: The results showed that the early recovery group had a shorter duration of sedation (P < 0.001), shorter duration of intensive care unit stay (P = 0.05), more rapid ventilator weaning (P < 0.001), and fewer pneumonia events (8.8% vs 39.1%) than the traditional recovery group. Wound- and vessel-related complications were not affected by the duration of sedation. CONCLUSIONS: Our study demonstrated that shortening the duration of postoperative sedation can effectively decrease the length of intensive care unit stay and reduce postoperative incidence of pneumonia without increasing wound- and vessel-related complications.

Frozen Fat Grafts Maintain Vascular Endothelial Growth Factor Expression and Mediate Angiogenesis During Adipose-Derived Stem Cell Enrichment for Soft Tissue Augmentation.

BACKGROUND: Fresh fat grafts are commonly used in both esthetic and reconstructive surgeries, but the graft resorption rate varies. Cryopreservation of unused fat for later touch-up is one option to resolve this variation. In our previous studies, we found that fat cryopreservation may be a practical strategy for storing fat tissue. To explore the cryopreservation method, we evaluated the role of vascular endothelial growth factor (VEGF) in human frozen fat grafts. METHODS: The concentration of VEGF in human frozen fat grafts subjected to different preservation times was determined using Western blotting and enzyme-linked immunosorbent assay. The angiogenic effect of frozen fat grafts was evaluated using a chorioallantoic membrane assay. Furthermore, the impact of adding human adipose-derived stem cells (hADSCs) or different concentrations of avastin (bevacizumab) to frozen fat grafts on angiogenesis was assessed. The viability of frozen fat grafts with or without hADSCs was evaluated using a nude mouse implantation study. Explanted fat tissues were examined on days 1, 4, 7, 14, 28, and 90, and morphological and histological analyses, immunohistochemistry, and enzyme-linked immunosorbent assay (VEGF concentration) were carried out. RESULTS: No significant difference in VEGF concentration between fresh and frozen fat was observed with respect to preservation duration. In the chorioallantoic membrane assay, frozen fat grafts with hADSCs displayed significantly enhanced angiogenesis. Avastin was found to decrease angiogenesis in frozen fat grafts. However, in the nude mouse implantation study, frozen fat grafts displayed VEGF maintenance, with the highest concentration observed on day 7. Adding hADSCs to the graft further increased the VEGF concentration and CD31 expression. Fat graft viability was found to be higher in the frozen fat grafts containing hADSCs than in grafts without hADSCs. CONCLUSIONS: Human fat grafts can maintain VEGF expression under frozen conditions for at least 12 months. The addition of hADSCs to the frozen fat graft could further enhance angiogenesis, VEGF expression, and fat cell viability.

Supermicrosurgical lymphovenous anastomosis for the treatment of recurrent cellulitis-associated lymphedema in the lower limb.

Recurrent leg cellulitis can damage the lymphatic system and result in chronic lymphedema. Antibiotic therapy is administered to prevent cellulitis; however, antibiotic-resistant bacteria frequently occur. Supermicrosurgical lymphovenous anastomosis (LVA) can play a role in stopping the vicious circle by improving lymph circulation. In the present report, we have described the case of a 40-year-old male patient with frequent cellulitis and subsequent left leg edema. Based on the lymphoscintigraphy findings, LVA was performed on the left leg (six anastomoses). One year later, the lymphedema had subsided without further cellulitis. Lymphoscintigraphy revealed no dermal backflow. Thus, LVA is a treatment option for recurrent cellulitis-associated lymphedema.

Using Various Skin Graft Techniques in Major Burn Reconstruction: A Lesson Learned From a Taiwanese Cornstarch Explosion.

PURPOSE: Four hundred and ninety-nine patients had burn injuries in an explosion in Taiwan on June 27, 2015, 24 were admitted to the intensive care units of Taipei Veterans General Hospital. This study details our experience with surgical management of these patients, focusing primarily on various skin graft techniques. MATERIALS AND METHODS: This single-center retrospective study included patients who underwent at least one of the previously mentioned skin graft techniques because of extensive skin defects. The demography, burn diagram, treatment modalities, postoperative outcome, and costs were all analyzed, and a comparison with traditional mesh skin grafts was performed. The literature was also reviewed. RESULTS: Fourteen patients underwent the Meek skin graft technique. Only 3 received ReCell and 1 cultured epithelial autograft (CEA) at separate time point. Overall, the autologous skin grafts, including Meek/ReCell/CEA were completed within 6 months. The average skin graft success rate was approximately 72.9%, 79.2%, and 38% in Meek, ReCell, and CEA, respectively. The infection rate was approximately 35.7%, 25%, and 100% in Meek, ReCell, and CEA, respectively. The average surgical cost and total medical cost were significantly higher in patients who underwent Meek/ReCell/CEA treatments. CONCLUSIONS: In our experience, Meek and ReCell treatments had acceptable success rates, but CEA treatment not. ReCell and CEA treatments are useful in the event of extremely limited donor sites, and they are fragile, easily infected, and technically challenging. These techniques also require longer hospitalization and tend to be more expensive, all factors that should be considered when assessing treatment options.

Intra-arterial injection of human adipose-derived stem cells improves viability of the random component of axial skin flaps in nude mice.

BACKGROUND: Skin flap necrosis is a common postoperative complication in reconstructive surgery. Recent evidence suggests that subcutaneously injected adipose-derived stem cells (ASCs) increase the viability of random skin flaps. Here, we examined whether intra-arterial human ASC administration could improve random component survival of axial skin flaps in nude mice. METHODS: Human ASCs isolated from a healthy volunteer by liposuction were injected into nude mice through the right femoral artery at a low (1 × 103 cells), medium (1 × 104 cells), or high (1 × 105 cells) dose. After ASC infusion, right superficial inferior epigastric vessels were ligated to create unipedicled superficial inferior epigastric artery (SIEA) flap with random extension. RESULTS: Flap survival was higher in mice from all three ASC-treated groups, and particularly the medium-dose group was 30% better, than in the control group. Histological examination demonstrated a significantly higher vascular density in the axial skin flap in nude mice treated with the medium ASC dose than in control mice. PKH26-labeled ASCs were identified in skin flaps of ASC-treated mice; some endothelial cells exhibited positive staining for human HLA-A. Compared to the control group, mice in ASC-treated groups had higher vascular endothelial growth factor levels and lower tumor necrosis factor α, interferon γ, and interleukin-6 levels. CONCLUSIONS: Intra-arterial human ASC administration increased the survival of axial skin flaps by attenuating inflammatory reactions and enhancing neovascularization. Intra-arterial ASC administration might yield a higher rate of these cells and of engraftment in the skin flaps. This approach may have a therapeutic role in increasing flap survival.

Review of preclinical and clinical studies of using cell-based therapy for secondary lymphedema.

Secondary lymphedema is associated with impaired lymph fluid drainage and remains incurable. Alternatively, cell-based therapy may pave the way for lymphedema treatment. We found 11 animal and seven human studies had been conducted from 2008 to 2018. Most studies showed great potential for this treatment modality. Emerging studies have focused on novel techniques, such as coupling cell therapy with lymph node transfer, or adding growth factors to cell therapy.

Dietary Supplementation with Hazelnut Oil Reduces Serum Hyperlipidemia and Ameliorates the Progression of Nonalcoholic Fatty Liver Disease in Hamsters Fed a High-Cholesterol Diet.

Objective: Hazelnut oil (HO) is rich in monounsaturated fatty acids and polyunsaturated fatty acids. This study intended to analyze the effects of hazelnut oil supplementation on the serum lipid profile and nonalcoholic fatty liver disease in hamsters fed a high-cholesterol (HC) diet. Methods: Hamsters were fed a basic diet (control group) and an HC diet (HC group) for 16 weeks (n = 10 in each group). Hamsters were fed an HC diet for four weeks to induce hyperlipidemia and were then fed an HC diet enriched with 5% (low-dose HC + HO group; n = 10) and 10% HO (high-dose HC + HO group; n = 10) for 12 weeks. Serum lipid levels, hepatic changes (including steatosis, inflammation, and fibrosis), and hepatic prooxidant-antioxidant status (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST)) were evaluated after the treatment period. Results: Hamsters in the control group showed normal serum lipid profiles, normal liver function, and moderate glycogen storage without hepatic steatosis. Hamsters in the HC group showed severe hyperlipidemia, severe hepatic steatosis, and moderate steatohepatitis (mononuclear cell and neutrophil infiltration, oval cell hyperplasia, and fibrosis). Compared to the HC group, both the low-dose and the high-dose HC + HO groups showed a significant reduction of hyperlipidemia (serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C levels)) and improved liver function (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). Additionally, compared to the HC group, intrahepatic triglyceride accumulation (IHTC) was significantly higher in the HC + HO group, while the incidence of steatohepatitis was significantly lower. The intake of the HC diet was associated with a higher level of lipid peroxidation (malondialdehyde, MDA) and a lower concentration of hepatic antioxidant enzymes (SOD, GPx, and GST), and all these factors were partially improved in the low-dose and high-dose HC + HO groups. Conclusions: Our findings indicate that the intake of HO reduced serum hyperlipidemia and oxidative stress and ameliorated the progression of nonalcoholic fatty liver disease in hamsters fed a high-cholesterol diet.

Adipose-derived stem cells-induced burn wound healing and regeneration of skin appendages in a novel skin island rat model.

BACKGROUND: The study of effectiveness of adipose-derived stem cells (ASCs) in treating burn wounds is still a developing field. The process of wound contraction in areas of loose skin is a major confounding factor in the evaluation and study of burn wound healing in animal models. METHODS: To evaluate the effect of local ASCs administration, deep partial thickness burn wounds were induced by 30 s application of hot copper plates in a novel skin island burn wound rat model to avoid interference from primary wound contraction. Skin islands were divided into two treatment groups-control group (n = 9) injected with PBS and ASCs-treated group (n = 9) injected with 5 × 10 ASCs intradermally. Progress in wound healing was checked at regular intervals after injury (on 1st, 2nd, 3rd, and 4th week) by measuring the mean wound area and analyzing the wound histologically and immunohistochemically, after unstitching the overlaying skin to expose the skin island. RESULTS: It was found that local intradermal injection of ASCs improved burn wound healing at all given time points when compared with control groups, especially in the first 2 weeks (p < 0.05). The percentage of live follicles increased gradually in the ASCs-treated groups compared with control groups between the 3rd and 4th weeks (p < 0.05). The vascular density and proliferating cell nuclear antigen index were also significantly increased in the ASCs-treated groups. CONCLUSION: Thus, in this study, a novel burn wound rat model with reduced interference from wound contraction has been put forth to investigate the therapeutic effects of local administration of ASCs on burn wound healing. Local injection of ASCs not only improved burn wound recovery but also enhanced angiogenesis and skin appendage regeneration.

Sphingosine-1-phosphate in Endothelial Cell Recellularization Improves Patency and Endothelialization of Decellularized Vascular Grafts In Vivo.

BACKGROUND: S1P has been shown to improve the endothelialization of decellularized vascular grafts in vitro. Here, we evaluated the potential of tissue-engineered vascular grafts (TEVGs) constructed by ECs and S1P on decellularized vascular scaffolds in a rat model. METHODS: Rat aorta was decellularized mainly by 0.1% SDS and characterized by histology. Rat ECs, were seeded onto decellularized scaffolds, and the viability of the ECs was evaluated by biochemical assays. Then, we investigated the in vivo patency rate and endothelialization for five groups of decellularized vascular grafts (each n = 6) in a rat abdominal aorta model for 14 days. The five groups included (1) rat allogenic aorta (RAA); (2) decellularized RAA (DRAA); (3) DRAA with S1P (DRAA/S1P); (4) DRAA with EC recellularization (DRAA/EC); and (5) DRAA with S1P and EC recellularization (DRAA/EC/S1P). RESULTS: In vitro, ECs were identified by the uptake of Dil-Ac-LDL. S1P enhanced the expression of syndecan-1 on ECs and supported the proliferation of ECs on decellularized vascular grafts. In vivo, RAA and DRAA/EC/S1P both had 100% patency without thrombus formation within 14 days. Better endothelialization, more wall structure maintenance and less inflammation were noted in the DRAA/EC/S1P group. In contrast, there was thrombus formation in the DRAA, DRAA/S1P and DRAA/EC groups. CONCLUSION: S1P could inhibit thrombus formation to improve the patency rate of EC-covered decellularized vascular grafts in vivo and may play an important role in the construction of TEVGs.

Determinants of Free Fasciocutaneous Flap Outcomes in Partial Hypopharyngeal Defects.

BACKGROUND: Most of the patients with hypopharyngeal cancer are still diagnosed with advanced stage, and total or partial pharyngectomy with free flap reconstruction is the mainstay of treatment. The aim of this study was to find out the possible risk factors related to surgical complications after free fasciocutaneous flap reconstruction for partial pharyngeal defect and its sequelae in the follow-up. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients with advanced hypopharyngeal cancer who received free fasciocutaneous flaps for partial pharyngeal defects reconstruction. From 2005 to 2015, 79 free fasciocutaneous flaps (59 free fasciocutaneous flaps and 20 anterolateral thigh flaps) were performed in our department. The risk factors for free flap outcome and complications were evaluated with multivariant linear regression model. RESULTS: The mean age of patients was 60.8 years with male predominance. The mean follow-up duration was 39.6 months. Most of the cases (97.5%) were in stage III or IV. Patients with comorbidities showed significant correlation to flap failure (95% confidence interval [CI] = 0.038 to 0.264, P = 0.10). Anastomosis style (end-to-side vs end-to-end) was the only operation-related factors significantly related to flap failure rate (18.8% vs 3.2%, 95% CI = 0.031 to 0.32, P = 0.18). Flap size was significantly associated with fistula formation (95% CI = -0.005 to 0.000, P = 0.38). CONCLUSIONS: In our experience, patients with comorbidities and end-to-side anastomosis illustrate significantly higher flap failure rate in free fasciocutaneous flap reconstruction of partial hypopharyngeal defect. Reconstruction with smaller flap size had higher possibility of fistula formation.

Porcine-induced pluripotent stem cell-derived osteoblast-like cells ameliorate trabecular bone mass of osteoporotic rats.

AIM: We created rat models of osteoporosis and verified a novel idea to recover bone mass via local cell transplantation. MATERIALS & METHODS: The rats were treated with ovariectomy, 0.1% calcium diet or 3 mg/kg body weight/day of prednisolone and porcine-induced pluripotent stem cell (piPSC)-derived osteoblast-like cells were transplanted into the medullary cavity of the left femurs. RESULTS: The piPSC-derived osteoblast-like cells exerted therapeutic potential on prednisolone treatment group, which confirmed by improvements in trabecular bone volume (15.93 ± 2.20%), bone surface/volume ratio (27.82 ± 1.40 1/mm), thickness (1.40 ± 0.01 mm), separation (0.99 ± 0.10 mm), number (1.13 ± 0.13 1/mm) and total porosity (84.06 ± 2.20%). CONCLUSION: These results first uncovered therapeutic potential of xenotransplantation with piPSCs for glucocorticoid-induced osteoporosis treatment in the rat models.