Trainability for cardiopulmonary fitness is low in patients with peripheral artery disease.

AIMS: In patients with peripheral arterial disease (PAD), exercise therapy is recommended to relieve leg symptoms, as noted in the 2016 AHA/ACC and 2017 ESC/ESVS guidelines. We assessed the trainability for cardiopulmonary fitness (CPF) and quality of life (QOL); three distinct patient types, namely, PAD, heart failure (HF), and stroke, were compared. METHODS AND RESULTS: This is a multicentre, retrospective analysis of prospectively collected data from three clinical studies. Data collected from 123 patients who completed 36 sessions of supervised aerobic training of moderate intensity were analysed, with 28 PAD, 55 HF, and 40 stroke patients totalling 123. Before and after training, cardiopulmonary exercise testing with non-invasive cardiac output monitoring and QOL evaluation using a 36-Item Short Form Survey (SF-36) were performed. Non-response was defined as a negative change in the post-training value compared with that in the pre-training value. The result showed an improvement in CPF in all three groups. However, cardiorespiratory fitness (CRF) increased by a lesser extent in the PAD group than in the HF and stroke groups; the physical and mental component scores (MCS) of SF-36 exhibited a similar pattern. Non-response rates of peak V˙O2, oxygen uptake efficiency slope, and MCS were higher in the PAD group. In the PAD group, non-responders regarding peak V˙O2 had a higher pulse wave velocity than responders. CONCLUSION: In patients with PAD following exercise therapy, CRF and QOL improved to a lesser extent on average; their non-response rate was also higher compared with that of HF or stroke patients. Therefore, a higher dose of exercise might be needed to elicit adaptation in PAD patients, especially those with high pulse wave velocity.

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury.

Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.

Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies.

The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide-polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide-polyglycolide/indomethacin, polylactide-polyglycolide/collagen, and polylactide-polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat.

Prediction for blood lactate during exercise using an artificial intelligence-Enabled electrocardiogram: a feasibility study.

Introduction: The acquisition of blood lactate concentration (BLC) during exercise is beneficial for endurance training, yet a convenient method to measure it remains unavailable. BLC and electrocardiogram (ECG) both exhibit variations with changes in exercise intensity and duration. In this study, we hypothesized that BLC during exercise can be predicted using ECG data. Methods: Thirty-one healthy participants underwent four cardiopulmonary exercise tests, including one incremental test and three constant work rate (CWR) tests at low, moderate, and high intensity. Venous blood samples were obtained immediately after each CWR test to measure BLC. A mathematical model was constructed using 31 trios of CWR tests, which utilized a residual network combined with long short-term memory to analyze every beat of lead II ECG waveform as 2D images. An artificial neural network was used to analyze variables such as the RR interval, age, sex, and body mass index. Results: The standard deviation of the fitting error was 0.12 mmol/L for low and moderate intensities, and 0.19 mmol/L for high intensity. Weighting analysis demonstrated that ECG data, including every beat of ECG waveform and RR interval, contribute predominantly. Conclusion: By employing 2D convolution and artificial neural network-based methods, BLC during exercise can be accurately estimated non-invasively using ECG data, which has potential applications in exercise training.

Comparison of long-term outcomes of complete vs. incomplete revascularization in elderly patients (≥75 years) with acute coronary syndrome and multi-vessel disease undergoing percutaneous coronary intervention.

Background: The optimal revascularization strategy for elderly patients with acute coronary syndrome (ACS) remains uncertain. We evaluated the impact of complete revascularization (CR) vs. incomplete revascularization (IR) in elderly ACS patients with multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI). Methods: Using registry data from 2011 to 2019, we conducted a propensity-score matched cohort study. Elderly patients (≥75 years) with ACS and MVD who underwent PCI were divided into CR and IR groups based on angiography during index hospitalization. Major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent non-fatal myocardial infarction, and any revascularization, were assessed at 3-year follow-up. Results: Among 1,018 enrolled patients, 496 (48.7%) underwent CR and 522 (51.3%) received IR. After 1:1 propensity-score matching, we analyzed 395 pairs. At 3-year follow-up, CR was significantly associated with lower MACE risk compared to IR (16.7% vs. 25.6%, HR = 0.65, 95% CI: 0.47-0.88, p = 0.006), driven by reduced all-cause mortality. This benefit was consistent across all pre-specified subgroups, particularly in ST segment elevation (STE)-ACS patients. In non-STE (NSTE)-ACS subgroup analysis, CR was also associated with a lower risk of cardiac mortality compared to IR (HR = 0.30, 95% CI: 0.12-0.75, p = 0.01). Conclusion: In elderly ACS patients with MVD undergoing PCI, CR demonstrates superior long-term outcomes compared to IR, irrespective of STE- or NSTE-ACS presentation.

Nanofibrous insulin/vildagliptin core-shell PLGA scaffold promotes diabetic wound healing.

Introduction: Slow wound repair in diabetes is a serious adverse event that often results in loss of a limb or disability. An advanced and encouraging vehicle is wanted to enhance clinically applicable diabetic wound care. Nanofibrous insulin/vildagliptin core-shell biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffolds to prolong the effective drug delivery of vildagliptin and insulin for the repair of diabetic wounds were prepared. Methods: To fabricate core-shell nanofibrous membranes, vildagliptin mixture with PLGA, and insulin solution were pumped via separate pumps into two differently sized capillary tubes that were coaxially electrospun. Results and Discussion: Nanofibrous core-shell scaffolds slowly released effective vildagliptin and insulin over 2 weeks in vitro migration assay and in vivo wound-healing models. Water contact angle (68.3 ± 8.5° vs. 121.4 ± 2.0°, p = 0.006) and peaked water absorbent capacity (376% ± 9% vs. 283% ± 24%, p = 0.003) of the insulin/vildagliptin core-shell nanofibrous membranes remarkably exceeded those of a control group. The insulin/vildagliptin-loaded core-shell nanofibers improved endothelial progenitor cells migration in vitro (762 ± 77 cells/mm2 vs. 424.4 ± 23 cells/mm2, p < 0.001), reduced the α-smooth muscle actin content in vivo (0.72 ± 0.23 vs. 2.07 ± 0.37, p < 0.001), and increased diabetic would recovery (1.9 ± 0.3 mm2 vs. 8.0 ± 1.4 mm2, p = 0.002). Core-shell insulin/vildagliptin-loaded nanofibers extend the drug delivery of insulin and vildagliptin and accelerate the repair of wounds associated with diabetes.

Red Disperse Azo Dye Side Chains Influence on Polyethylene Terephthalate Dyeing Performances in Supercritical Carbon Dioxide Media.

Supercritical carbon dioxide dyeing (SDD) as a dyeing media not only provides a friendly dyeing environment but also significantly increases polymeric dyeing performances ascribed to strong azo dye affinity. Disperse azo dyes have shown to be highly efficient dyeing agents due to their facile coupling synthesis, side chains position, and length tunability to optimize absorption properties. Herein, we first synthesize two series of disperse red azo dyes via a coupling chemical route. Further, we investigate the position of the electron withdrawing group and alkyl chains length impact onto the absorption and color fastness properties. Upon synthesis, 1H NMR and mass spectroscopy were used to characterize our newly synthesized series dye structure. Also, according to spectroscopic characterization, the functional group positions as well as the alkyl chains length have a major impact on the dye series maximum light absorption wavelength and performance. We have performed SDD dyeing of polyethylene terephthalate woven and determined each dye color fastness, we find that a reduced electron withdrawing effect and alkyl chains increase reduce color-fastness performances. Overall, our dyes exhibited a good resistance against detergent water, perspiration, abrasion, and friction.

Tuning pro-survival effects of human induced pluripotent stem cell-derived exosomes using elastin-like polypeptides.

Exosome-based regenerative therapies are potentially easier to manufacture and safer to apply compared to cell-based therapies. However, many questions remain about how to bio-manufacture reproducible and potent exosomes using animal-free reagents. Here we evaluate the hypothesis that designer biomaterial substrates can be used to alter the potency of exosomes secreted by human induced pluripotent stem cells (iPSCs). Two animal-free designer matrices were fabricated based on recombinant elastin-like polypeptides (ELPs): one including a cell-adhesive RGD ligand and a second with a non-adhesive RDG peptide. While iPSCs cultured on these two substrates and Matrigel-coated controls had similar levels of proliferation, the RDG-ELP substrate significantly increased protein expression of stemness markers OCT4 and SOX2 and suppressed spontaneous differentiation compared to those on RGD-ELP. The pro-survival potency of iPSC-derived exosomes was evaluated using three distinct stress tests: serum starvation in murine fibroblasts, hypoxia in human endothelial cells, and hyperosmolarity in canine kidney cells. In all three cases, exosomes produced by iPSCs grown on RDG-ELP substrates had similar pro-survival effects to those produced using iPSCs grown on Matrigel, while use of RGD-ELP substrates led to significantly reduced exosome potency. These data demonstrate that recombinant substrates can be designed for the robust bio-manufacturing of iPSC-derived, pro-survival exosomes.

Enhanced Diabetic Wound Healing Using Electrospun Biocompatible PLGA-Based Saxagliptin Fibrous Membranes.

Delayed diabetic wound healing is an adverse event that frequently leads to limb disability or loss. A novel and promising vehicle for the treatment of diabetic wounds is required for clinical purposes. The biocompatible and resorbable poly (lactic-co-glycolic acid) (PLGA)-based fibrous membranes prepared by electrospinning that provide a sustained discharge of saxagliptin for diabetic wound healing were fabricated. The concentration of released saxagliptin in Dulbecco's phosphate-buffered saline was analyzed for 30 days using high-performance liquid chromatography. The effectiveness of the eluted saxagliptin was identified using an endothelial progenitor cell migration assay in vitro and a diabetic wound healing in vivo. Greater hydrophilicity and water storage were shown in the saxagliptin-incorporated PLGA membranes than in the pristine PLGA membranes (both p < 0.001). For diabetic wound healing, the saxagliptin membranes accelerated the wound closure rate, the dermal thickness, and the heme oxygenase-1 level over the follicle areas compared to those in the pristine PLGA group at two weeks post-treatment. The saxagliptin group also had remarkably higher expressions of insulin-like growth factor I expression and transforming growth factor-ß1 than the control group (p = 0.009 and p < 0.001, respectively) in diabetic wounds after treatment. The electrospun PLGA-based saxagliptin membranes exhibited excellent biomechanical and biological features that enhanced diabetic wound closure and increased the antioxidant activity, cellular granulation, and functionality.

Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis.

The inhibition of dipeptidyl peptidase-4 (DPP4) significantly enhances the wound closure rate in diabetic patients with chronic foot ulcers. DPP4 inhibitors are only prescribed for enteral, but topical administration, if feasible, to a wound would have more encouraging outcomes. Nanofibrous drug-eluting poly-D-L-lactide-glycolide (PLGA) membranes that sustainably release a high concentration of vildagliptin were prepared to accelerate wound healing in diabetes. Solutions of vildagliptin and PLGA in hexafluoroisopropanol were electrospun into nanofibrous biodegradable membranes. The concentration of the drug released in vitro from the vildagliptin-eluting PLGA membranes was evaluated, and it was found that effective bioactivity of vildagliptin can be discharged from the nanofibrous vildagliptin-eluting membranes for 30 days. Additionally, the electrospun nanofibrous PLGA membranes modified by blending with vildagliptin had smaller fiber diameters (336.0 ± 69.1 nm vs. 743.6 ± 334.3 nm, p < 0.001) and pore areas (3405 ± 1437 nm2 vs. 8826 ± 4906 nm2, p < 0.001), as well as a higher hydrophilicity value (95.2 ± 2.2° vs. 113.9 ± 4.9°, p = 0.004), and showed a better water-retention ability within 24 h compared with PLGA membranes. The vildagliptin-eluting PLGA membrane also enhanced the diabetic wound closure rate for two weeks (11.4 ± 3.0 vs. 18.7 ± 2.6 %, p < 0.001) and the level of the angiogenesis using CD31 expression (1.73 ± 0.39 vs. 0.45 ± 0.17 p = 0.006 for Western blot; 2.2 ± 0.5 vs. 0.7 ± 0.1, p < 0.001 for immunofluorescence). These results demonstrate that nanofibrous drug-eluting PLGA membranes loaded with vildagliptin are an effective agent for sustained drug release and, therefore, for accelerating cutaneous wound healing in the management of diabetic wounds.

Nanofiber-Based Odor-Free Medical Mask Fabrication Using Polyvinyl Butyral and Eucalyptus Anti Odor Agent.

Following the 2020 COVID-19 worldwide outbreak, many countries adopted sanitary and safety measures to safeguard public health such as wearing medical face mask. While face masks became a necessity for people, disadvantages impede their long period wearing such as uncomfortable breathability and odor. The intermediate layer of the medical face mask is composed of porous non-woven fabric to block external particles while maintaining breathability. To overcome aforementioned limitation, this study uses electrospinning to design and fabricate odorless face masks via the use of aromatic oil. Eucalyptus essential oil is encapsulated through mixing and layer-by-layer by hydrophobic polyvinyl butyral and further used to fabricate the medical mask intermediate layer. We found that adding 0.2 g of eucalyptus into polyvinyl butyral fabric through mixing results in the deodorization rate of 80% after 2 h, with fabric thickness of 440.9 µm, and melt-blown non-woven fabric thickness of 981.7 µm. The Particle Filtration Efficiency of 98.3%, Bacterial Filtration Efficiency above 99.9%, and the differential pressure of 4.7 mm H2O/cm2 meet the CNS 14774 standard on medical face masks. Therefore, this study successfully proved that this type of masks' middle layer not only effectively protects against coronavirus, but also provides better scents and makes it more comfortable for consumers.

Human Skin-Inspired Electrospun Patterned Robust Strain-Insensitive Pressure Sensors and Wearable Flexible Light-Emitting Diodes.

Wearable skin-inspired electronic skins present remarkable outgrowth in recent years because their promising comfort device integration, lightweight, and mechanically robust durable characteristics led to significant progresses in wearable sensors and optoelectronics. Wearable electronic devices demand real-time applicability and factors such as complex fabrication steps, manufacturing cost, and reliable and durable performances, severely limiting the utilization. Herein, we nominate a scalable solution-processable electrospun patterned candidate capable of forming ultralong mechanically robust nano-microdimensional fibers with higher uniformity. Nanofibrous patterned substrates present surface energy and silver nanoparticle crystallization shifts, contributing to strain-sensitive and -insensitive conductive electrodes (10 000 cycles of 50% strain). Synergistic robust stress releasing and durable electromechanical behavior engenders stretchable durable health sensors, strain-insensitive pressure sensors (sensitivity of ∼83 kPa-1 and 5000 durable cycles), robust alternating current electroluminescent displays, and flexible organic light-emitting diodes (20% improved luminescence and 300 flex endurance of 2 mm bend radius).

Thermoplastic Starch with Poly(butylene adipate-co-terephthalate) Blends Foamed by Supercritical Carbon Dioxide.

Starch-based biodegradable foams with a high starch content are developed using industrial starch as the base material and supercritical CO2 as blowing or foaming agents. The superior cushioning properties of these foams can lead to competitiveness in the market. Despite this, a weak melting strength property of starch is not sufficient to hold the foaming agents within it. Due to the rapid diffusion of foaming gas into the environment, it is difficult for starch to maintain pore structure in starch foams. Therefore, producing starch foam by using supercritical CO2 foaming gas faces severe challenges. To overcome this, we have synthesized thermoplastic starch (TPS) by dispersing starch into water or glycerin. Consecutively, the TPS surface was modified by compatibilizer silane A (SA) to improve the dispersion with poly(butylene adipate-co-terephthalate) (PBAT) to become (TPS with SA)/PBAT composite foam. Furthermore, the foam-forming process was optimized by varying the ratios of TPS and PBAT under different forming temperatures of 85 °C to 105 °C, and two different pressures, 17 Mpa and 23 Mpa were studied in detail. The obtained results indicate that the SA surface modification on TPS can influence the great compatibility with PBAT blended foams (foam density: 0.16 g/cm3); whereas unmodified TPS and PBAT (foam density: 0.349 g/cm3) exhibit high foam density, rigid foam structure, and poor tensile properties. In addition, we have found that the 80% TPS/20% PBAT foam can be achieved with good flexible properties. Because of this flexibility, lightweight and environment-friendly nature, we have the opportunity to resolve the strong demands from the packing market.

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum.

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

Bacteremia (Sepsis), Hepatorenal Syndrome, and Serum Creatinine Levels Rather than Types or Microbial Patterns Predicted the Short-Term Survival of Cirrhotic Patients Complicated with Spontaneous Bacterial Peritonitis.

(1) Background: Spontaneous bacterial peritonitis (SBP) is a major and severe complication in cirrhosis patients with ascites. Over the years, advance in antibiotic treatment has led to changes in microbial patterns in some regions, including the emergence of extended-spectrum beta-lactamases resistant (ESBL)-producing bacteria and an increase in Gram-positive bacteria (GPC). In addition, three SBP types (classic SBP, culture-negative neutrophilic ascites (CNNA), and monomicrobial non-neutrocytic bacterascites (MNB)), may also have different prognoses. Therefore, the study aimed to investigate the microbial pattern and the predictors of short-term outcomes in patients with SBP. (2) Methods: Patients discharged with a diagnosis of the first episode of SBP between January 2006 and July 2017 were enrolled. Patients' clinical, demographic, hematological, and biochemical data were obtained at diagnosis, and the model for end-stage liver disease (MELD)-based scores were calculated accordingly. Patients were followed up until February 2018 or until death. (3) Results: A total of 327 patients were analyzed. The prevalence of classic SBP was nearly equivalent to CNNA. As for the microbial pattern, Gram-negative bacillus (GNB) remained more prevalent than GPC (75 vs. 25%), with E. coli being the most common bacterial species, followed by K. Pneumoniae and then Staphylococcus. The percentage of ESBL strain in culture-positive patients was 10.9%. By univariable and multivariable logistic regression survival analysis, there was no significant difference in predicting short-term mortality among the three SBP types, neither between GNB vs. GPC nor between ESBL- and non-ESBL-producing bacteria. Only bacteremia (sepsis), hepatorenal syndrome (HRS), and serum creatinine (Cr) were independent predictors of in-hospital and 3-month mortality, whereas HRS and Cr were independent predictors of 6-month mortality. (4) Conclusions: SBP types, Gram stain result, and ESBL strain did not affect survival. Only bacteremia (sepsis), HRS, and serum Cr independently predicted the short-term mortality in patients with SBP.

Telmisartan Loaded Nanofibers Enhance Re-Endothelialization and Inhibit Neointimal Hyperplasia.

Stent implantation impairs local endothelial function and may be associated with subsequent adverse cardiovascular events. Telmisartan, an angiotensin II receptor blocker that has unique peroxisome proliferator-activated-receptor-gamma-mediated effects on cardiovascular disease, has been shown to enhance endothelial function and limit neointimal hyperplasia. This study utilized hybrid biodegradable/stent nanofibers to facilitate sustained and local delivery of telmisartan to injured arterial vessels. Telmisartan and poly(d,l)-lactide-co-glycolide (PLGA) (75:25) were dissolved in hexafluoroisopropyl alcohol and electrospun into biodegradable nanofibrous tubes which were coated onto metal stents. By releasing 20% of the loaded telmisartan in 30 days, these hybrid biodegradable/stent telmisartan-loaded nanofibers increased the migration of endothelial progenitor cells in vitro, promoted endothelialization, and reduced intimal hyperplasia. As such, this work provides insights into the use of PLGA nanofibers for treating patients with an increased risk of stent restenosis.

Antibacterial Activity and Protection Efficiency of Polyvinyl Butyral Nanofibrous Membrane Containing Thymol Prepared through Vertical Electrospinning.

Human safety, health management, and disease transmission prevention have become crucial tasks in the present COVID-19 pandemic situation. Masks are widely available and create a safer and disease transmission-free environment. This study presents a facile method of fabricating masks through electrospinning nontoxic polyvinyl butyral (PVB) polymeric matrix with the antibacterial component Thymol, a natural phenol monoterpene. Based on the results of Japanese Industrial Standards and American Association of Textile Chemists and Colorists methods, the maximum antibacterial value of the mask against Gram-positive and Gram-negative bacteria was 5.6 and 6.4, respectively. Moreover, vertical electrospinning was performed to prepare Thymol/PVB nanofiber masks, and the effects of parameters on the submicron particulate filtration efficiency (PFE), differential pressure, and bacterial filtration efficiency (BFE) were determined. Thorough optimization of the small-diameter nanofiber-based antibacterial mask led to denser accumulation and improved PFE and pressure difference; the mask was thus noted to meet the present pandemic requirements. The as-developed nanofibrous masks have the antibacterial activity suggested by the National Standard of the Republic of China (CNS 14774) for general medical masks. Their BFE reaches 99.4%, with a pressure difference of <5 mmH2O/cm2. The mask can safeguard human health and promote a healthy environment.

Codelivery of Sustainable Antimicrobial Agents and Platelet-Derived Growth Factor via Biodegradable Nanofibers for Repair of Diabetic Infectious Wounds.

More than half of diabetic wounds demonstrate clinical signs of infection at presentation and lead to poor outcomes. This work develops coaxial sheath-core nanofibrous poly(lactide-co-glycolide) (PLGA) scaffolds that are loaded with bioactive antibiotics and platelet-derived growth factor (PDGF) for the repair of diabetic infectious wounds. PDGF and PLGA/antibiotic solutions were pumped, respectively, into two independent capillary tubings for coaxial electrospinning to prepare biodegradable sheath-core nanofibers. Spun nanofibrous scaffolds sustainably released PDGF, vancomycin, and gentamicin for 3 weeks. The scaffolds also reduced the phosphatase and tensin homologue content, enhanced the amount of angiogenesis marker (CD31) around the wound area, and accelerated healing in the early stage of infected diabetic wound repair. Antibiotic/biomolecule-loaded PLGA nanofibers may provide a very effective way to aid tissue regeneration at the sites of infected diabetic wounds.

Core-shell insulin-loaded nanofibrous scaffolds for repairing diabetic wounds.

Patients with diabetes mellitus have up to a 15% lifetime risk of non-healing and poorly healing wounds. This work develops core-shell nanofibrous bioactive insulin-loaded poly-D-L-lactide-glycolide (PLGA) scaffolds that release insulin in a sustained manner for repairing wounds in diabetic rats. To prepare the biodegradable core-shell nanofibers, PLGA and insulin solutions were fed into two capillary tubes of different sizes that were coaxially electrospun using two independent pumps. The scaffolds sustainably released insulin for four weeks. The hydrophilicity and water-containing capacity of core-shell nanofibrous insulin/PLGA scaffolds significantly exceeded those of blended nanofibrous scaffolds. The nanofibrous core-shell insulin-loaded scaffold reduced the amount of type I collagen in vitro, increased the transforming growth factor-beta content in vivo, and promoted diabetic would repair. The core-shell insulin-loaded nanofibrous scaffolds prolong the release of insulin and promote diabetic wound healing.

Nanofibrous vildagliptin-eluting stents enhance re-endothelialization and reduce neointimal formation in diabetes: in vitro and in vivo.

BACKGROUND: The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated. RESEARCH DESIGN AND METHODS: In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography. RESULTS: Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group. CONCLUSION: The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases.