Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

BACKGROUND: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. METHODS: Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. RESULTS: Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6Chigh monocyte aggregates near the thrombus, and diminished neutrophils and Ly6Chigh macrophages in the cranial thrombus part compared with isotype-treated controls. Depletion of neutrophils 1 day after thrombus initiation did not phenocopy P-selectin inhibition but led to larger thrombi compared with untreated controls. In vitro, P-selectin enhanced human leukocyte function as P-selectin-coated beads increased reactive oxygen species production by neutrophils and tissue factor expression of classical monocytes. Accordingly, P-selectin inhibition reduced oxidative burst in the thrombus and tissue factor expression in the adjacent vessel wall. Moreover, blocking P-selectin reduced thrombus density determined by scanning electron microscopy and increased urokinase-type plasminogen activator levels in the thrombus, which accelerated caudal fibrin degradation from day 3 to day 14. This accelerated thrombus resolution as thrombus volume declined more rapidly after blocking P-selectin. CONCLUSIONS: Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.

Undetected Long-Term Hypothyroidism Caused by Hashimoto's Thyroiditis with Severe Cardiac Complications - An Unusual Case of Child Neglect.

Neglect in childhood may often be undetected for a long time. Parents of patients of handicapped children are often unable to cope with multiple medical and psychological problems that exist with such patients despite support by the health services [Jacobi G, Dettmeyer R, Banaschak S, Brosig B et al. Child abuse and neglect: diagnosis and management. Dtsch Arztebl Int 2010; 107: 231-240]. This is especially true for patients with trisomy 21 because they frequently suffer from complex congenital heart disease, feeding difficulties and behaviour anomalies. Additionally, various degrees of hypothyroidism are very frequent in Down syndrome but rarely lead - as in our case - to a life threatening disease.

Organ doses in preterm and full-term neonates and infants - a retrospective study on 1,064 chest radiographs.

BACKGROUND: Chest radiography is the most frequent X-ray examination performed in the neonatal period. However, commonly used dosimetric entities do not describe the radiation risk sufficiently. OBJECTIVE: The aim of this study was to investigate selected organ doses and total body dose of chest radiographs in preterm and full-term neonates and infants. MATERIALS AND METHODS: In this retrospective study, we evaluated 1,064 chest radiographs of 136 preterm and 305 full-term babies with respect to field size and centering. We calculated the entrance dose from the dose-area product. Upper and lower field borders referred to the corresponding vertebrae. We calculated individual organ doses of the thyroid, the breast, the liver and active bone marrow for each chest radiograph using the neonatal PCXMC program, a Monte Carlo program for calculating patient doses in medical X-ray examinations. RESULTS: The median field size of chest radiographs ranged from 90 cm2 in preterm neonates at birth to 290 cm2 in full-term infants at the age of 6 months. Median values of entrance dose varied, depending on age, from 15 µGy to 25 µGy. The median organ doses ranged 1-20 µSv for the thyroid, 3-30 µSv for the breast, 2-20 µSv for the liver and 0.5-3.5 µSv for the bone marrow in preterm and full-term neonates and infants, respectively. CONCLUSION: The analysis of chest radiographs in preterm and full-term neonates and infants revealed high variability in field size. By contrast, the entrance dose varied to a minor extent. Organ dose calculations using the PCXMC program might be a valuable tool to calculate the individual radiation risk in neonates and infants.

Intrarenal reflux, an overlooked entity - retrospective analysis of 1,166 voiding cysturethrographies in children.

BACKGROUND: The significance of intrarenal reflux as a risk factor for renal scarring and hypertension has been discussed. Fluoroscopic detection of intrarenal reflux depends on the equipment, the training of the radiologists and the timing of spot film acquisition. OBJECTIVE: To evaluate the prevalence of intrarenal reflux and its association with age, gender, grade of vesico-uretero-renal reflux and the renal segments affected. MATERIALS AND METHODS: We retrospectively analysed 1,166 voiding cysturethrographies. Patients' ages ranged from 1 day old to 19 years old. Vesico-uretero-renal reflux was detected in 209 female and 164 male patients using a standardised technique with digital pulsed fluoroscopy. The point in time and grade of reflux were documented with spot films. All radiographs showing reflux were assessed for the occurrence of intrarenal reflux. RESULTS: Intrarenal reflux was detected in 41 of 373 (11%) patients with vesico-uretero-renal reflux. Unilateral intrarenal reflux was found in 30 patients and bilateral in 11. The left kidney was more frequently affected than the right (31 versus 21). Only patients younger than 9 years of age were affected (mean age: 1.6 years, median: 0.8 years). Intrarenal reflux was independent of gender and was most frequently observed in grade IV reflux (59.6%) and less often in grade V (23.1%) and grade III (17.3%). CONCLUSION: Intrarenal reflux in this study was detected in 11% of patients with vesico-uretero-renal reflux, predominantly with reflux grade IV and in patients younger than 4 years old.

Second follow-up of a German cohort on childhood cancer incidence after exposure to postnatal diagnostic x-ray.

Studies on children exposed to ionising radiation by computed tomography (CT) indicate an increased risk of leukemia and central nervous system (CNS) tumors. Evidence of the risks associated with diagnostic x-ray examinations, the most frequent examination in pediatric radiology, in which the radiation dose is up to 750 times lower compared to CT examinations, is less clear. This study presents results of the second follow-up for the risk of childhood cancer in a cohort of children (<15 years) with diagnostic x-ray exposure at a large German hospital during 1976-2003 followed for additional 10 years until 2016. With a latency period of 6 months, 92 998 children contributed 794 549 person-years. The median effective dose was 7 µSv. Hundred incident cancer cases were identified: 35 leukemia, 13 lymphomas, 12 CNS tumors, 15 blastomas, 15 sarcomas and 10 other solid tumors, consisting of six germ cells tumors, three thyroid cancers and one adrenocortical carcinoma. For all cancer cases combined the standardised incidence ratio (SIR) was 1.14 (95% confidence interval (CI) 0.93-1.39), for leukemia 1.15 (95% CI 0.63-1.61), for lymphomas 1.03 (95% CI 0.55-1.76), for CNS tumors 0.65 (95% CI 0.34-1.14), for blastomas 1.77 (95% CI 0.91-2.91), for sarcomas 1.28 (95% CI 0.71-2.11) and for other solid tumors 2.38 (95% CI 1.14-4.38). Dose-response analysis using Poisson regression revealed no significant trend for dose groups. Results did not differ substantially with a latency period of 2 years for all cancer entities and 5 years for solid tumors in sensitivity analyses. Overall, the null results of the first follow-up were confirmed. Although an association between radiation exposure and a risk for certain solid tumors like thyroid cancer is known, the significantly increased SIR in the group of other solid tumors must be critically interpreted in the context of the small number of cases and the very low doses of radiation exposure in this group.

Fetal cardiac time intervals in healthy pregnancies - an observational study by fetal ECG (Monica Healthcare System).

BACKGROUND: Fetal electrocardiogram (fECG) can detect QRS signals in fetuses from as early as 17 weeks' gestation; however, the technique is limited by the minute size of the fetal signal relative to noise ratio. The aim of this study was to evaluate precise fetal cardiac time intervals (fCTIs) with the help of a newly developed fetal ECG device (Monica Healthcare System). METHODS: In a prospective manner we included 15-18 healthy fetuses per gestational week from 32 weeks onwards. The small and wearable Monica AN24 monitoring system uses standard ECG electrodes placed on the maternal abdomen to monitor fECG, maternal ECG and uterine electromyogram (EMG). Fetal CTIs were estimated on 1000 averaged fetal heart beats. Detection was deemed successful if there was a global signal loss of less than 30% and an analysis loss of the Monica AN24 signal separation analysis of less than 50%. Fetal CTIs were determined visually by three independent measurements. RESULTS: A total of 149 fECGs were performed. After applying the requirements 117 fECGs remained for CTI analysis. While the onset and termination of P-wave and QRS-complex could be easily identified in most ECG patterns (97% for P-wave, PQ and PR interval and 100% for QRS-complex), the T-wave was detectable in only 41% of the datasets. The CTI results were comparable to other available methods such as fetal magnetocardiography (fMCG). CONCLUSIONS: Although limited and preclinical in its use, fECG (Monica Healthcare System) could be an additional useful tool to detect precise fCTIs from 32 weeks' gestational age onwards.

[Intrapartum Foetal Heart Rate Monitoring and Rate of Caesarean Section: A National Survey]. / CTG-Analyse und Sectiorate ­ Ergebnisse einer deutschlandweiten Umfrage.

INTRODUCTION: The rate of Caesarean section has dramatically increased in recent decades. Foetal scalp blood sampling and computer software analysing foetal heart rate detection should help in the decision-making for or against Caesarean section. The main aim of this study was to examine how these 2 factors influence the Caesarean section rate. METHODS: A national survey of all maternity units in Germany was undertaken using a self-reported questionnaire via crowd sourcing. All variables were collected as categorised data sets. Using these data sets, correlation coefficients were calculated. The correlations were additionally analysed using visual mosaic plots. RESULTS: 97 questionnaires were analysed. There were several strong correlations between variables in the data set. Particularly, hospitals that assessed the foetal heart rate in the normal range (110-160 bpm) according to the current FIGO guidelines had a lower C-section rate. CONCLUSION: Computer-assisted foetal heart rate assessment that is based on the FIGO guidelines correlated with a lower Caesarean section rate. The use and further development of computer-based cardiotocograph assessment analysis should be continued.

Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial.

BACKGROUND: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. OBJECTIVE: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. STUDY DESIGN: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. RESULTS: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). CONCLUSION: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses.

Frequency of Miscarriage/Stillbirth and Terminations of Pregnancy Among Women With Congenital Heart Disease in Germany, Hungary and Japan.

BACKGROUND: The 2011 guidelines of the European Society of Cardiology (ESC) on the management of cardiovascular diseases during pregnancy define the maternal predictors for neonatal complications. The aim of this study was to determine whether these are associated with an increased number of miscarriages/stillbirths and terminations of pregnancy (TOPs) also in patients with congenital heart defects (CHD). METHODS AND RESULTS: The 634 women from Germany, Hungary and Japan were surveyed concerning the issues of sexuality and reproductive health, as well as their general life situation and medical care. 25% of the recorded pregnancies in women with CHD resulted in miscarriage, stillbirth or TOP. Affecting 16.8% of all recorded pregnancies, miscarriages or stillbirths occurred more frequently than in the general population and more than previously recorded for patients with CHD. TOP occurred in 8% of the surveyed pregnancies. Underlying maternal predictors for neonatal events had an influence on the number of TOP; among those with underlying predictors, TOP was recorded 3-fold more than in those without such predictors (15.6% vs. 5.5%). Remarkably, a significant deficit regarding the level of information on potential pregnancy-associated risks was observed in all 3 participating countries. CONCLUSIONS: Pregnant women with CHD should always be treated and counseled individually by cardiologists, gynecologists, obstetricians and anesthetists with appropriate expert knowledge. (Circ J 2016; 80: 1846-1851).

Mechanisms of vasculogenesis in 3D fibrin matrices mediated by the interaction of adipose-derived stem cells and endothelial cells.

Vascularization of tissue-engineered constructs is essential to provide sufficient nutrient supply and hemostasis after implantation into target sites. Co-cultures of adipose-derived stem cells (ASC) with outgrowth endothelial cells (OEC) in fibrin gels were shown to provide an effective possibility to induce vasculogenesis in vitro. However, the mechanisms of the interaction between these two cell types remain unclear so far. The aim of this study was to evaluate differences of direct and indirect stimulation of ASC-induced vasculogenesis, the influence of ASC on network stabilization and molecular mechanisms involved in vascular structure formation. Endothelial cells (EC) were embedded in fibrin gels either containing non-coated or ASC-coated microcarrier beads as well as ASC alone. Moreover, EC-seeded constructs incubated with ASC-conditioned medium were used in addition to constructs with ASC seeded on top. Vascular network formation was visualized by green fluorescent protein expressing cells or immunostaining for CD31 and quantified. RT-qPCR of cells derived from co-cultures in fibrin was performed to evaluate changes in the expression of EC marker genes during the first week of culture. Moreover, angiogenesis-related protein levels were measured by performing angiogenesis proteome profiler arrays. The results demonstrate that proximity of endothelial cells and ASC is required for network formation and ASC stabilize EC networks by developing pericyte characteristics. We further showed that ASC induce controlled vessel growth by secreting pro-angiogenic and regulatory proteins. This study reveals angiogenic protein profiles involved in EC/ASC interactions in fibrin matrices and confirms the usability of OEC/ASC co-cultures for autologous vascular tissue engineering.

Pregnancy-related obstetric and cardiologic problems in women after atrial switch operation for transposition of the great arteries.

BACKGROUND: The number of women with congenital heart disease reaching reproductive age has increased due to therapeutic advances. The aim of this study was to examine obstetric and cardiac problems during pregnancy after Mustard/Senning repair for transposition of the great arteries. METHODS AND RESULTS: Sixty pregnancies in 34 women from 3 centers were studied. The women were interviewed, and their records reviewed for clinical status and diagnostic evaluation. Age range was 16-34 years during first pregnancy, and all were in a low functional class. There were 11 miscarriages and 5 abortions. Of 44 successful pregnancies, 20 were vaginal deliveries and 24, cesarean sections. A total of 25% were delivered prematurely. Thirteen babies had birth weight <2,500g. Deterioration in functional class occurred in 7 pregnancies, without recovery in 5. Deterioration in systolic function occurred in 4 of 44 echocardiographically documented pregnancies, without recovery in 75%. In 2 women resuscitation was necessary during delivery, in 1, supraventricular tachycardia occurred during labor. CONCLUSIONS: Pregnancy is usually well-tolerated, but outcome is unforeseeable and life-threatening problems can occur. These women belong in cardiac care conducted by experienced congenital cardiologists, who systematically check for typical residua. The pregnancy should be planned and gynecologists/obstetricians with special expertise integrated into the consultations. During delivery a congenital cardiologist, and an anesthetist experienced in congenital cardiology, should be present for possible severe cardiac events.

Effect of maternal obesity with and without gestational diabetes on offspring subcutaneous and preperitoneal adipose tissue development from birth up to year-1.

BACKGROUND: Maternal obesity and gestational diabetes mellitus (GDM) may independently influence offspring fat mass and metabolic disease susceptibility. In this pilot study, body composition and fat distribution in offspring from obese women with and without GDM and lean women were assessed within the 1st year of life, and maternal and newborn plasma factors were related to offspring adipose tissue distribution. METHODS: Serum and plasma samples from pregnant obese women with (n = 16) or without (n = 13) GDM and normoglycemic lean women (n = 15) at 3rd trimester and offspring cord plasma were used for analyzing lipid profiles, insulin and adipokine levels. At week-1 and 6, month-4 and year-1, offspring anthropometrics and skinfold thickness (SFT) were measured and abdominal subcutaneous (SCA) and preperitoneal adipose tissue (PPA) were determined by ultrasonography. RESULTS: Cord insulin was significantly increased in the GDM group, whereas levels of cord leptin, total and high molecular weight (HMW) adiponectin were similar between the groups. Neonates of the GDM group showed significantly higher SFT and fat mass until week-6 and significantly increased SCA at week-1 compared to the lean group that persisted as strong trend at week-6. Interestingly, PPA in neonates of the GDM group was significantly elevated at week-1 compared to both the lean and obese group. At month-4 and year-1, significant differences in adipose tissue growth between the groups were not observed. Multiple linear regression analyses revealed that cord insulin levels are independently related to neonatal PPA that showed significant relation to PPA development at year-1. Maternal fasted C-peptide and HMW adiponectin levels at 3rd trimester emerged to be determinants for PPA at week-1. CONCLUSION: Maternal pregravid obesity combined with GDM leads to newborn hyperinsulinemia and increased offspring fat mass until week-6, whereas pregravid obesity without GDM does not. This strongly suggests the pivotal role of GDM in the adverse offspring outcome. Maternal C-peptide and HMW adiponectin levels in pregnancy emerge to be predictive for elevated PPA in newborns and might be indicative for the obesity risk at later life. Altogether, the findings from our pilot study warrant evaluation in long-term studies. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004370.

Conversion coefficients for determining organ doses in paediatric spine radiography.

BACKGROUND: Knowledge of organ and effective doses achieved during paediatric x-ray examinations is an important prerequisite for assessment of radiation burden to the patient. OBJECTIVE: Conversion coefficients for reconstruction of organ and effective doses from entrance doses for segmental spine radiographs of 0-, 1-, 5-, 10-, 15- and 30-year-old patients are provided regarding the Guidelines of Good Radiographic Technique of the European Commission. MATERIALS AND METHODS: Using the personal computer program PCXMC developed by the Finnish Centre for Radiation and Nuclear Safety (Säteilyturvakeskus STUK), conversion coefficients for conventional segmental spine radiographs were calculated performing Monte Carlo simulations in mathematical hermaphrodite phantom models describing patients of different ages. The clinical variation of beam collimation was taken into consideration by defining optimal and suboptimal radiation field settings. RESULTS: Conversion coefficients for the reconstruction of organ doses in about 40 organs and tissues from measured entrance doses during cervical, thoracic and lumbar spine radiographs of 0-, 1-, 5-, 10-, 15- and 30-year-old patients were calculated for the standard sagittal and lateral beam projections and the standard focus detector distance of 115 cm. CONCLUSION: The conversion coefficients presented may be used for organ dose assessments from entrance doses measured during spine radiographs of patients of all age groups and all field settings within the optimal and suboptimal standard field settings.

Conversion coefficients for determining organ doses in paediatric pelvis and hip joint radiography.

BACKGROUND: Knowledge of organ and effective doses achieved during paediatric X-ray examinations is an important prerequisite for assessment of radiation burden to the patient. OBJECTIVE: Conversion coefficients for reconstruction of organ and effective doses from entrance doses for pelvis and hip joint radiographs of 0-, 1-, 5-, 10-, 15- and 30-year-old patients are provided regarding the Guidelines of Good Radiographic Technique of the European Commission. MATERIALS AND METHODS: Using the personal computer program PCXMC developed by the Finnish Centre for Radiation and Nuclear Safety (Säteilyturvakeskus STUK), conversion coefficients for conventional pelvis and hip joint radiographs were calculated by performing Monte Carlo simulations in mathematical hermaphrodite phantom models representing patients of different ages. The clinical variation of radiation field settings was taken into consideration by defining optimal and suboptimal standard field settings. RESULTS: Conversion coefficients for the reconstruction of organ doses in about 40 organs and tissues from measured entrance doses during pelvis and hip joint radiographs of 0-, 1-, 5-, 10-, 15- and 30-year-old patients were calculated for the standard sagittal beam projection and the standard focus detector distance of 115 cm. CONCLUSION: The conversion coefficients presented can be used for organ dose assessments from entrance doses measured during pelvis and hip joint radiographs of children and young adults with all field settings within the optimal and suboptimal standard field settings.

Comparison of Decellularized Human Dermal Scaffolds versus Bovine Collagen/Elastin Matrices for Engineering of Soft-Tissue Flaps.

BACKGROUND: Free flap-based soft-tissue reconstruction comes at the price of donor-site morbidity. The arteriovenous loop (AVL) technique can overcome this issue by allowing for the de novo generation of axially vascularized soft-tissue flaps from vein grafts embedded into different matrices. Application of the AVL technique has been limited by insufficient long-term volume retention and poor tissue stability. The authors investigated the suitability of a novel human dermal scaffold to improve volume retention and tissue stability. METHODS: AVLs were created in 28 immunocompetent rats and embedded in either decellularized human dermal scaffolds (experimental group, n = 14) (Epiflex) or bovine collagen/elastin matrices (control group, n = 14) (MatriDerm) in subcutaneous polytetrafluoroethylene chambers. The weight and volume of engineered tissues, the extent of angiogenesis, and the proportion of proliferating cells were compared between groups on postoperative days (PODs) 21 and 28 by means of immunohistochemistry and micro-computed tomography. RESULTS: On POD 28, both groups displayed homogeneous microvascular networks on histopathology and micro-computed tomography. Mean microvessel counts and surface areas and the percentage of proliferating cells did not differ between the groups. However, the experimental human scaffold group displayed significantly smaller volume loss and significantly less tissue degradation compared with bovine matrix controls (volume retention, 102% ± 5% versus 27% ± 7% on POD 21, and 79% ± 12% versus 12% ± 7% on POD 28, respectively; P < 0.0001). CONCLUSION: Compared with bovine matrices, decellularized human scaffolds allow for superior volume retention and tissue stability of de novo engineered soft-tissue AVL flaps in rats. CLINICAL RELEVANCE STATEMENT: AVLs allow for the de novo generation of vascularized soft-tissue flaps. However, insufficient long-term volume retention is still an issue. The authors' study shows that decellularized human matrices guarantee superior volume stability of de novo grown soft-tissue flaps in rats.

Recent advances in harnessing biological macromolecules for wound management: A review.

Wound dressings (WDs) are an essential component of wound management and serve as an artificial barrier to isolate the injured site from the external environment, thereby helping to prevent exogenous infections and supporting healing. However, maintaining a moist wound environment, providing protection from infection, good biocompatibility, and allowing for gas exchange, remain a challenge in device design. Functional wound dressings (FWDs) prepared from hybrid biological macromolecule-based materials can enhance efficacy of these systems for skin wound management. This review aims to provide an overview of the state-of-the-art FWDs within the field of wound management, with a specific focus on hybrid biomaterials, techniques, and applications developed over the past five years. In addition, we highlight the incorporation of biological macromolecules in WDs, the emergence of smart WDs, and discuss the existing challenges and future prospects for the development of advanced WDs.

Silk Fibroin/Wool Keratin Composite Scaffold with Hierarchical Fibrous and Porous Structure.

The present study describes a silk microfiber reinforced meniscus scaffold (SMRMS) with hierarchical fibrous and porous structure made from silk fibroin (SF) and wool keratin (WK) using electrospinning and freeze-drying technology. This study focuses on the morphology, secondary structure, mechanical properties, and water absorption properties of the scaffold. The cytotoxicity and biocompatibility of SMRMS are assessed in vivo and in vitro. The scaffold shows hierarchical fibrous and porous structure, hierarchical pore size distribution (ranges from 50 to 650 µm), robust mechanical properties (compression strength can reach at 2.8 MPa), and stable biodegradability. A positive growth condition revealed by in vitro cytotoxicity testing indicates that the scaffold is not hazardous to cells. In vivo assessments of biocompatibility reveal that only a mild inflammatory reaction is present in implanted rat tissue. Meniscal scaffold made of SF/WK composite shows a potential application prospect in the meniscal repair engineering field with its development.

Woven Vascular Stent-Grafts with Surface Modification of Silk Fibroin-Based Paclitaxel/Metformin Microspheres.

In-stent restenosis caused by tumor ingrowth increases the risk of secondary surgery for patients with abdominal aortic aneurysms (AAA) because conventional vascular stent grafts suffer from mechanical fatigue, thrombosis, and endothelial hyperplasia. For that, we report a woven vascular stent-graft with robust mechanical properties, biocompatibility, and drug delivery functions to inhibit thrombosis and the growth of AAA. Paclitaxel (PTX)/metformin (MET)-loaded silk fibroin (SF) microspheres were self-assembly synthesized by emulsification-precipitation technology and layer-by-layer coated on the surface of a woven stent via electrostatic bonding. The woven vascular stent-graft before and after coating drug-loaded membranes were characterized and analyzed systematically. The results show that small-sized drug-loaded microspheres increased the specific surface area and promoted the dissolution/release of drugs. The stent-grafts with drug-loaded membranes exhibited a slow drug-release profile more for than 70 h and low water permeability at 158.33 ± 17.56 mL/cm2·min. The combination of PTX and MET inhibited the growth of human umbilical vein endothelial cells. Therefore, it was possible to generate dual-drug-loaded woven vascular stent-grafts to achieve the more effective treatment of AAA.

Biodegradable, Self-Reinforcing Vascular Grafts for In Situ Tissue Engineering Approaches.

Clinically available small-diameter synthetic vascular grafts (SDVGs) have unsatisfactory patency rates due to impaired graft healing. Therefore, autologous implants are still the gold standard for small vessel replacement. Bioresorbable SDVGs may be an alternative, but many polymers have inadequate biomechanical properties that lead to graft failure. To overcome these limitations, a new biodegradable SDVG is developed to ensure safe use until adequate new tissue is formed. SDVGs are electrospun using a polymer blend composed of thermoplastic polyurethane (TPU) and a new self-reinforcing TP(U-urea) (TPUU). Biocompatibility is tested in vitro by cell seeding and hemocompatibility tests. In vivo performance is evaluated in rats over a period for up to six months. Autologous rat aortic implants serve as a control group. Scanning electron microscopy, micro-computed tomography (µCT), histology, and gene expression analyses are applied. TPU/TPUU grafts show significant improvement of biomechanical properties after water incubation and exhibit excellent cyto- and hemocompatibility. All grafts remain patent, and biomechanical properties are sufficient despite wall thinning. No inflammation, aneurysms, intimal hyperplasia, or thrombus formation are observed. Evaluation of graft healing shows similar gene expression profiles of TPU/TPUU and autologous conduits. These new biodegradable, self-reinforcing SDVGs may be promising candidates for clinical use in the future.