Application status and prospect of biodegradable polymer stents in pancreatobiliary disease / 中华肝胆外科杂志

Endoscopic stent implantation is one of the main methods for the treatment of biliary and pancreatic diseases. At present, the commonly used biliary and pancreatic stents are mainly plastic and metal stents which are still have some deficiencies in clinical applications, and the emergence of the new type of biodegradable polymer materials is expected to achieve the purpose of treatment to overcome these shortcomings. It is a potential hope to break through the bottleneck of endoscopic treatment of choleopancreatic diseases. Previous animal experiments and human clinical studies have preliminarily shown its safety and effectiveness, which can effectively solve some problems of bile and pancreatic duct stenosis and so on. Biodegradable polymer stents have been widely studied, but their clinical application progress is slow and not yet popular, and it has gradually become a research hotspot in recent years . This article discusses the research status and development direction of biodegradable polymer stents in biliary and pancreatic diseases.

Evaluating the long-term prognosis of coronary artery disease patients undergoing percutaneous coronary intervention by risk stratification with ACC/AHA classification of coronary lesions / 中华心血管病杂志

Objective@#To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions.@*Methods@#Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months.@*Results@#Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively.@*Conclusions@#The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

Evaluating the long-term prognosis of coronary artery disease patients undergoing percutaneous coronary intervention by risk stratification with ACC/AHA classification of coronary lesions / 中华心血管病杂志

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions: The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

In vitro experimental study on the mechanical properties of biodegradable polymer stents / 生物医学工程学杂志

experimental test for mechanical properties of a vascular stent is a main method to evaluate its effectiveness and safety, which is of great significance to the clinical applications. In this study, a comparative study of planar, V-groove and radial compression methods for the radial support property test were performed, and the effects of compression rate and circumferential position on the test results were conducted. Based on the three-point bending method, the influences of compression rate and circumferential position on flexibility were also explored. And then a best test proposal was selected to evaluate the radial support property and flexibility of the three self-designed stents and the comparative biodegradable vascular stent (BVS) (BVS1.1, Abbott Vascular, USA) with different outside diameters of 1.4 mm, 1.7 mm and 2.4 mm. The results show that the developing trends of the compression load with the compression displacement measured by the three radial support property test methods are the same, but normalized radial force values are quite different. The planar compression method is more suitable for comparing the radial support properties of stents with different diameters and structures. Compression rate has no obvious effect on the testing results of both the radial support property and flexibility. Compression circumferential position has a great impact on testing radial support property with the planar or V-groove compression methods and testing flexibility with three-point bending method. The radial support properties of all the three self-designed stents are improved at a certain degree compared to that of the BVS stent. The study has better guide significance and reference value for testing mechanical properties of vascular stents.

Value of SYNTAX revascularization index on evaluating the long-term prognosis of coronary artery disease patients with biodegradable polymer drug-eluting stents implantation / 中华心血管病杂志

Objective@#To explore the value of SYNTAX revascularization index (SRI) on evaluating the long-term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug-eluting stents (BP-DES) and define the best threshold of SRI for predicting all-cause mortality in these patients.@*Methods@#Data used in this study derived from the I-LOVE-IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, non-inferiority study. A total of 1 829 patients implanted with BP-DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, myocardial infarction(MI), stroke, and/or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut-off point of SRI for 48-month all-cause mortality. The Cox regression analysis was used to identify independent predictors of the all-cause death and PoCE at 48 months.@*Results@#Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all-cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut-off point to predict the all-cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48-month all-cause mortality (HR=2.06, 95%CI 1.25-3.38) and PoCE (HR=1.34, 95%CI 1.09-1.66).@*Conclusions@#SRI serves as a good index for predicting long-term prognosis and SRI<65% is an independent predictor of 48-month PoCE and all-cause mortality for CAD patients with BP-DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

Long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases / 中华心血管病杂志

Objective@#To evaluate the long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases.@*Methods@#CREDIT Ⅱ trial was a prospective, multicenter, randomized, controlled study, conducted at 15 Chinese cardiac centres from November 2013 to December 2014. In this analysis, eligible patients for coronary stenting (n=419) were randomized to receive either the EXCEL2 stent (n=208) or the EXCEL stent (n=211). The primary endpoint was target lesion failure (TLF) at 3 years after PCI defined as a composite endpoints of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularization (CI-TLR). Secondary endpoints included patient-oriented composite endpoint (PoCE) including all-cause death, all MI, or any revascularization at 3 years and independent components, and stent thrombosis according to Academic Research Consortium′s (ARC) definition.@*Results@#Among 419 enrolled patients, 413 (98.6%) patients completed 3-year clinical follow-up. Compared with the EXCEL group, 3-year TLF (5.4%(11/204) vs. 11.5% (24/209), P=0.025) and PoCE (9.8% (20/204) vs. 20.1% (42/209), P=0.003) were significantly lower in the EXCEL2 group. The cumulative event rate of CI-TLR (2.0% (4/204) vs. 5.7% (12/209), P=0.042) and any revascularization (4.9% (10/204) vs. 14.4% (30/209), P=0.001) were statistically lower in the EXCEL2 group than in the EXCEL group. There were no significant difference between two groups in terms of all-cause death and all MI. Rates of stent thrombosis were low without significant difference between the two groups (EXCEL2 vs. EXCEL, 1.0% (2/204) vs. 2.9% (6/209), P=0.285).@*Conclusion@#3-year clinical follow-up results demonstrate that EXCEL2 stents are effective and safe in treating CAD patients with de novo coronary lesions.

Effectiveness and Safety of Biolimus A9™-Eluting stEnt in Patients with AcUTe Coronary sYndrome; A Multicenter, Observational Study (BEAUTY Study)

PURPOSE: This study sought to determine the 1-year clinical effectiveness and safety of a biodegradable, polymer-containing Biolimus A9™-eluting stent (BES) in Korean patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: A total of 1000 ACS patients with 1251 lesions who underwent implantation of BESs at 22 centers in Korea were enrolled between May 2011 and July 2013. We assessed major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinical-driven target vessel revascularization at 12 months. RESULTS: Patient mean age was 62.6±11.4 years. 72.8% of the patients were male, 28.5% had diabetes, 32.8% had multi-vessel disease (MVD), and 47.9% presented with acute MI (AMI). The mean global registry of acute coronary events risk score of all patients was 103.0±27.6. The number of stents per patient was 1.3±0.6. The incidences of MACE and definite stent thrombosis at 12 months were 3.9% and 0.2%, respectively. On multivariate Cox-regression analysis, age ≥65 years was identified as an independent predictors of 1-year MACE (hazard ratio=2.474; 95% confidence interval=1.202−5.091). Subgroup analyses revealed no significant differences in the incidence of MACE between patients with and without diabetes (4.3% vs. 3.7%, p=0.667), between those who presented with and without AMI (4.4% vs. 3.4%, p=0.403), and between those with and without MVD (4.6% vs. 3.5%, p=0.387). CONCLUSION: Our study demonstrated excellent 1-year clinical outcomes of BES implantation in patients at low-risk for ACS.

Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent for the treatment of de novo coronary lesions: 5-year results of the TARGET Ⅱ trial / 中华心血管病杂志

Objective@#This study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) in patients with moderate-complex coronary lesions (including patients with small vessel disease, long lesion and multi vessel disease), and to validate the ability of the SYNTAX score (SS) to predict clinical outcomes in patients treated with FIREHAWK stent. @*Methods@#TARGETⅡ was a prospective, multicenter, single-arm clinical trial, a total of 730 patients who underwent percutaneous coronary intervention (PCI) of de novo lesions in native coronary arteries in 24 medical centers in China from August 2011 to February 2012 were enrolled in this study. All patients were exclusively treated with the FIREHAWK stent. Clinical data including patients with diabetes, small vessel disease, long lesion and multi vessel disease were analyzed. The primary composite endpoint was the target lesion failure (TLF) of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR). The secondary composite endpoint was patient-oriented endpoint (PoCE), a composite of all death, all myocardial in farction (MI), or any repeat revascularization; definite/probable stent thrombosis (ST) (including acute, late, and very late thrombosis) . SS was calculated in lesions with stenosis more than 50% with coronary artery diameter greater than 1.5 mm. Patients were grouped by tertiles of SS (≤7, >7 to ≤12, >12). Follow-up was performed up to 5 years. @*Results@#A total of 730 patients were enrolled in the TARGET Ⅱ trial. The average SS was 10.9±6.9. 683 (93.6%) patients completed 5-year clinical follow-up. The 5-year incidence of TLF was 8.5%(58/683). The incidence of TLF components was as follows: cardiac death 2.0%(14/683), TV-MI 4.4%(30/683), TLR 3.4%(23/683). The incidence of PoCE was 16.4%(112/683). The incidence of definite/probable stent thrombosis was 0.7%(5/683).Multivariable Cox regression analysis showed that the diabetes subgroup (HR=1.123, 95%CI 0.623-2.026, P=0.699), the small vessel disease subgroup (HR=0.909, 95%CI 0.526-1.570, P=0.732), the long lesion subgroup (HR=1.561, 95%CI 0.922-2.640, P=0.097), and the multi vessel disease subgroup (HR=1.062, 95%CI 0.611-1.846, P=0.830) did not increase the HR of TLF compared with the counterpart subgroups. Multivariable Cox regression analysis showed that the hazard of TLF was not increased in the middle and high SS groups as compared with the low SS group (HR=1.203,95%CI 0.607-2.385,P=0.597;HR=1.548,95%CI 0.829-2.892,P=0.171). @*Conclusions@#The 5 years follow-up results of TARGET Ⅱ trial shows that the biodegradable polymer of FIREHAWK stents have long-lasting safety and efficacy for patients with moderate-complex coronary lesions. SS is not the predicting factor for the occurrence of TLF in FIREHAWK treated patients with moderate-complex coronary lesions. Trial Registration Clinical Trials.gov, NCT0141264.

Poly(DL-lactide)-degrading enzyme production by immobilized Actinomadura keratinilytica strain T16-1 in a 5-L fermenter under various fermentation processes

Background: Poly(DL-lactic acid), or PDLLA, is a biodegradable polymer that can be hydrolyzed by various types of enzymes. The protease produced by Actinomadura keratinilytica strain T16-1 was previously reported to have PDLLA depolymerase activity. However, few studies have reported on PDLLA-degrading enzyme production by bacteria. Therefore, the aims of this study were to determine a suitable immobilization material for PDLLA-degrading enzyme production and optimize PDLLA-degrading enzyme production by using immobilized A. keratinilytica strain T16-1 under various fermentation process conditions in a stirrer fermenter. Results: Among the tested immobilization materials, a scrub pad was the best immobilizer, giving an enzyme activity of 30.03 U/mL in a shake-flask scale. The maximum enzyme activity was obtained at aeration 0.25 vvm, agitation 170 rpm, 45°C, and 48 h of cultivation time. Under these conditions, a PDLLA-degrading enzyme production of 766.33 U/mL with 15.97 U/mL·h productivity was observed using batch fermentation in a 5-L stirrer fermenter. Increased enzyme activity and productivity were observed in repeated-batch (942.67 U/mL and 19.64 U/mL·h) and continuous fermentation (796.43 U/mL and 16.58 U/mL·h) at a dilution rate of 0.013/h. Scaled-up production of the enzyme in a 10-L stirrer bioreactor using the optimized conditions showed a maximum enzyme activity of 578.67 U/mL and a productivity of 12.06 U/mL·h. Conclusions: This research successfully scaled-up the enzyme production to 5 and 10 L in a stirrer fermenter and is helpful for many applications of poly(lactic acid).

Physicochemical properties and in vitro degradation of a novel collagen scaffold material from basa fish (Pangasisus haniltoa) skin / 第二军医大学学报

Objective To prepare a novel collagen scaffold material using Basa fish (Pangasisus haniltoa) skin as the ingredient and to analyze the structural characteristics, physical properties and degradability of the prepared material, so as to explore whether Basa fish can replace terrestrial mammals for preparing a novel collagen scaffold material. Methods Basa fish skins were lyophilized to obtain the membrane material after repeated degreasing, decolorization and dedoping. Crude protein content was determined by the Kjeldahl method. Structure of the materials and its pore size and distribution were analyzed by scanning electron microscopy (SEM). Porosity was measured by the liquid displacement technique, and tensile strength was tested using universal testing machine. The changes of viscosity with temperatures were detected to determine the denaturation temperature of the material.The material was immersed in the phosphate-buffered solution (0.1 mol/L, pH 7.4), which was placed in a constant temperature shaker at 37°, and the water absorption and weight loss rates of the material were detected. Results The crude protein content of the collagen scaffold material was 95.2%, with visually uniform thickness. SEM photographs showed that one side of the material had a rough surface and porous structure, on which varying sizes of pores distributed uniformly; the other side was smooth with dense pores. The porosity of the material was (55.50±1.94)%, thickness was (0.66±0.10) mm and tensile strength was (18.82±0.94) MPa. The denaturation temperature of the material was 34° before thermo-crosslinking and 36° after thermo-crosslinking. The water absorption of the material was (379.77±77.81)% at 48 h. At 28 d after thermo-crosslinking, the degradation rate was (80.22±2.49)%, and the pH value of buffer was 6.67±0.05. Conclusion The collagen scaffold material from Basa fish skin can be made into the biological membrane with uniform thickness, and the membrane comprises double structures: dense layer and loose layer. This material exhibits excellent mechanical strength and appropriate denaturation temperature, but its degradation is fast, which needs further improvement.

Poly-hydroxybutyrate (PHB) production by Halomonas elongata BK AG 18 indigenous from salty mud crater at central Java Indonesia

Aims: Bioplastic is a biodegradable polymer produced by particular microorganism as a secondary metabolite. Some halophilic bacteria belonging to Halomonas genus have been reported to be a potential of polyhydroxybutyrate (PHB) producer. This study aims to explore the potential of an indigenous halophilic bacterial isolate, H. elongata BK-AG18, as bioplastic producer. The indication as bioplastics producer was evaluated by growing in nile red-containing medium and bacterial colonies displayed bright orange fluorescent under ultraviolet light. Methodology and results: Bioplastic production by H. elongata BK-AG 18 was achieved using modified glucosecontained High Medium (HM) after incubated in a rotary shaker for 22 h, 37 °C, 150 rpm. The bioplastic was extracted with chloroform and sodium hypochlorite (1:1) and precipitated in methanol. The highest yield of bioplastic production was 21.36% of the dried bacterial cell weight. The structural characterizations of the bioplastics using Fourier transformed infrared (FTIR), 1H and 13C nuclear magnetic resonances (NMR) spectroscopies showed high similarity to the spectral pattern of poly-hydroxybutyrate (PHB). Further characterization using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed that the decomposition and melting temperature at 266 °C and 166.5 °C of the PHB, respectively. The result of PHB has a low degree of crystallinity (9.5%) that close to the rubber-like polymer. Conclusion, significance and impact of study: This study revealed the high potential of H. elongata BK-AG 18 as PHB producer with high mechanical properties.

Production of Polyhydroxybutyrate by Bacillus axaraqunsis BIPC01 using Petrochemical Wastewater as Carbon Source

The aim of this study was to use petrochemical wastewater as the source of carbon for the production of polyhydroxyalkanoates (PHA) in an effort to decrease its cost of production. For this purpose, PHA producing bacteria were isolated from the petrochemical wastewater of Bandar Imam, Iran. The purified colonies were screened for PHA by Sudan Black B and Nile Blue A staining. Among positively stained bacteria, the best PHA producer was selected on the basis of cell growth, PHA content and the monomer composition of PHA. The phenotypic and genotypic identification this isolate showed it to be Bacillus axaraqunsis. The PHA was produced at a cell density of about 9.46 g/l of maximum concentration of 6.33g/l l, corresponding to 66% of cell dry weight. These results showed that B. axaraqunsis BIPC01 could be a potent PHA producer using wastewater for industrial purpose and simultaneously reducing the environmental pollution.

Clinical Investigation of Biodegradable Polymer Sirolimns-eluting Stents in Treating the Patients With Diffuse Long Coronary Lesions / 中国循环杂志

Objective: To evaluate the efficacy and safety of overlapping biodegradable polymer sirolimus-eluting stents (EXCEL) in treating the patients with diffuse long coronary lesions (total stent length for per lesion>60 mm). Methods: A total of 71 patients with diffuse long coronary lesions with overlapped EXcellstents implantation in our hospital from 2010-08 to 2012-05 were retrospectively studied. The average age of patients was (62.85 ± 10.26) years and 74.56%with male gender. The clinical endpoints were the major adverse cardiac events (MACE) at in-hospital time and at 2-year follow-up period. Results: The average target lesion was implanted (2.61 ± 0.52) stents, the mean stent diameter was (3.21 ± 0.35) mm and the length was (73.34 ± 13.11) mm. The in-hospital MACE rate was 4.23%, the 2-year target vessel revascularization and MACE rates were 9.86%and 18.31%respectively. Cox regression analysis indicated that smoking (HR 12.102, 95%CI 1.460-100.309, P=0.021), previous history of MI (HR 11.948, 95%CI 1.144-124.726, P=0.038) and previous history of PCI (HR 0.097, 95%CI 0.010-0.990, P=0.049) were the independent risk factors of out of hospital MACE occurrence. Conclusion: EXcellstent implantation was safe and effective for treating the patients with diffuse long coronary lesions, the long term follow-up study revealed that there was the increased risk for MACE and target vessel revascularization.

A novel biodegradable polymer-coated cobalt-chromium alloy sirolimus-eluting stent：evaluation in a porcine model / 中国介入心脏病学杂志

Objective To assess the safety and efifcacy of a novel biodegradable polymer-coated Cobalt-Chromium alloy sirolimus-eluting stent in a porcine model. Methods Bare metal stents (BMS) (n=15), commercial available EXcellstents (n=21), and Cobalt-Chromium alloy PLAG-coated sirolimus-eluting stents (Co-P-SES) (n=21) were implanted in left anterior descending coronary (LAD, n=28)and left circumflex coronary (LCX, n=13), and right coronary artery (RCA, n=16) of 30 mini-pigs randomly. Coronary angiography was performed 28 days, 90 days and 180 days after the stenting procedure to evaluate luminal loss (LL), and then, histomorphology analysis was performed. Results 28 days and 91 days after the implantation, there were no significant differences in LL, neointimal area, Inflammation score and endothelialization score among the three groups. 28 days after the implantation, better endothelialization was observed in Co-P-SES group compared with EXcellgroup under scanning electron microscope. 182 days after the implantation, there were larger lumen area and less neointimal area in Co-P-SES group compared with EXcellgroup under similar internal elastic lamina area[(4.31±0.94) mm2 vs. (2.62±1.17) mm2, P=0.020];[(1.87±0.53) mm2 vs. (0.84±0.41) mm2, P=0.004]with statistical significance. Conclusions The novel biodegradable polymer-coated Cobalt-Chromium alloy sirolimus-eluting stents showed similar safety compared with commercial available EXcellstents. There would be a better potential of the novel stent on inhibiting the neointimal proliferation and endothelialization. However, further preclinical study including long term endpoints and clinical study should be conducted in order to evaluate the safety and effectiveness of the novel Co-P-SES.

In vitro comparative study of white and dark polycaprolactone trifumarate in situ cross-linkable scaffolds seeded with rat bone marrow stromal cells

OBJECTIVE: Dark poly(caprolactone) trifumarate is a successful candidate for use as a bone tissue engineering scaffold. Recently, a white polymeric scaffold was developed that shows a shorter synthesis time and is more convenient for tissue-staining work. This is an in vitro comparative study of both the white and dark scaffolds. METHODS: Both white and dark poly(caprolactone) trifumarate macromers were characterized via Fourier transform infrared spectroscopy before being chemically cross-linked and molded into disc-shaped scaffolds. Biodegradability was assessed by percentage weight loss on days 7, 14, 28, 42 and 56 (n = 5) after immersion in 10% serum-supplemented medium or distilled water. Static cell seeding was employed in which isolated and characterized rat bone marrow stromal cells were seeded directly onto the scaffold surface. Seeded scaffolds were subjected to a series of biochemical assays and scanning electron microscopy at specified time intervals for up to 28 days of incubation. RESULTS: The degradation of the white scaffold was significantly lower compared with the dark scaffold but was within the acceptable time range for bone-healing processes. The deoxyribonucleic acid and collagen contents increased up to day 28 with no significant difference between the two scaffolds, but the glycosaminoglycan content was slightly higher in the white scaffold throughout 14 days of incubation. Scanning electron microscopy at days 1 and 14 revealed cellular growth and attachment. CONCLUSIONS: There was no cell growth advantage between the two forms, but the white scaffold had a slower biodegradability rate, suggesting that the newly synthesized poly(caprolactone) trifumarate is more suitable for use as a bone tissue engineering scaffold.

Development and in vitro characterization of metronidazole loaded chitosan microspheres for delivery to periodontal pocket.

The aim of the present work was to develop drug delivery system for localized controlled release of metronidazole following insertion into and/or around the periodontal pocket. This would ensure increased local drug concentration at the periodontal site to maintain an effective concentration over an extended period of time and a decrease in superfluous distribution of the drug to other body organs with a subsequent decrease in side effects. In the present work, metronidazole loaded chitosan microspheres were prepared by external gelation technique using tripolyphosphate as the cross-linker. The drug to polymer ratio was chosen at three levels: 1:4, 1:5 and 1:6 (by weight) and tripolyphosphate concentration also at three levels: 6, 12 and 18 (%). The microspheres were characterized for surface morphology, particle size, drug entrapment efficiency, swelling, erosion, bioadhesion and drug release profile. Nearly spherical, rough and porous particles (size ~ 800 μm) were obtained. Drug entrapment efficiency was found to be in the range of 60-75%. Percentage swelling, erosion and bioadhesion ranged from 10-25%, 5-15% and 43-59% respectively. The results indicated that formulation of metronidazole in chitosan microspheres could be utilized as a potential drug delivery system to periodontal pocket.

THE THREE DIMENSIONAL FINITE ELEMENT ANALYSIS OF STRESS DISTRIBUTION AND DISPLACEMENT IN MANDIBLE ACCORDING TO TREATMENT MODALITIES OF MANDIBULAR ANGLE FRACTURES

Study on the drug during coronary stent in animal / 国际生物医学工程杂志

Objective To explore the feasibility of clinical application of biodegradable polymer-coated drug-eluting stent. Methods Thirty each of the drug-eluting stent or bare-metal stents were implanted randomly into the anterior descending arteries, circumflex and right canine coronary arteries of thirty healthy pigs. The pathological examination was taken at 2 weeks to 6 months after coronary angiography to investigate the inflammation, thrombosis and endothelialization. Results Macroscopic observation of the stented arteries demonstrated complete incorporation of stent wires into the arterial wall and smooth vessel lumens. There were no significant differences existing between two kinds of the stents in terms of thrombosis, inflammation and endothelialization. The lumen loss in the biodegradable polymer-coated drug-eluting stent group is less than that in the bare-metal stent group. Conclusion The biodegradable polymer-coated drug-eluting stent is promising with good biocom-patibility, blood compatibility and phyaicochemical stability after being implanted into pig coronary arteries. The blood vessel transplanted with the drug-eluting stents maintains a high patency rate due to rapid endothelialization.

Six-month results of a biodegradable polymer and rapamycin-coating stent for coronary artery disease / 老年心脏病学杂志（英文版）

Objective To assess the safety and efficacy of a novel biodegradable polymer and rapamycin-coating stent, the EXCEL stent, in the treatment of coronary artery disease (CAD), as compared with the CypherTM stent. Methods In this prospective, non-randomized study, 60 consecutive patients with symptomatic CAD received either an EXCEL stent (n=32), or a CypherTM stent(n=28),according to their respective treatment intention. Follow-up angiography was performed at a mean of 180±40 days. The primary endpoint of the study was the occurrence of a major adverse cardiac event (MACE), including death, myocardial infarction, or target-vessel revascularization during the 6 months after stenting. The secondary end points included the in-stent late luminal loss (LLL), percentage of in-stent stenosis of the luminal diameter, and the rate of restenosis (luminal narrowing of 50 percent or more) at 6 months. Results There were no significant differences between the two groups in baseline characteristics, including the distribution of target vessel and lesion types. During the follow up period of 6 months, there were no occurrences of MACE in either group. Twenty-seven patients(84%) in the EXCEL group and 10 (36 %) in the CypherTM group underwent quantitative coronary angiography at 6 months. For these patients, no restenosis occurred, and there were no differences in the in-stent stenosis of the luminal diameter (5.98±5.52% vs 5.21 ±6.3%,P＞0.05) and the LLL (-0.02±0.09 mm vs -0.01±0.07 mm, P＞0.05). Conclusions Compared with the CypherTM stent, the EXCEL Stent with biodegradable polymer and rapamycin-coating showed similar efficacy in the prevention of neointimal proliferation, restenosis, and associated clinical events in CAD patients.

One-Year Outcomes of Biodegradable Polymer Sirolimus-Eluting Stents for Patients With Coronary Artery Disease:Pilot Registry From a China Single Center / 中国循环杂志

Objective:To evaluate one-year efficacy and safety of sirolimus-eluting stent with biodegradable polymer coating (EXCEL stent) in treating patients with coronary artery disease. Methods:One hundred consecutive hospitalized patients with coronary artery diseases exclusively treated with EXCEL stents were prospectively enrolled.After undergoing porcutaneous coronary intervention (PCI) all patients received dual anti-platelet therapy with clopidogrel and aspirin for 6 months and followed by aspirin alone.The primary end point was major adverse cardiac events(MACE) at 12 months.The secondary end points included binary in-stent restenosis rate(ISR)measured by quantitative coronary angiography (QCA) analysis at mean 8 months post the index PCI procedure,and MACE at 30 days and 6 months. Results:All patients were successfully treated with EXCEL stents during PCI procedure.Among all 153 target lesions,127 lesions were type B2/C complex lesions (83.0%).The mean length and diameter of the target lesions were 29.42?15.90 mm and 3.17?0.53 mm,respectively.A total of 211 EXCEL stents were implanted with average stent number of 2.02?1.53 per patient.The mean stent length and diameter were 35.34?17.35 mm and 3.23?0.46 mm,respectively.Four patients (4.0%) reached the primary end point at 12 months,which were 4 target lesion re-PCI due to ISR.No death,MI,or in-stent thrombosis occurred during the 6-month aspirin treatment alone after comleting 6-month dual anti-platelet therapy.QCA analysis of 112 le- sions of 75 patients showed 3.6% (4/112) of in-stent restenosis and 5.4% (6/112) of in-segment restenosis. Conclusions:The initial registry study showed that comparison with the published data from previous pivotal studies of others drug-eluting stents,the EXCEL stent revealed similarly incidence of 12-month ISR and/or MACE for the real world patients with coronary artery disease.The anti-platelet regimen of 6-month clopidogrel treatment after EXCEL implantation was safe.This con- clusion requires further investigation by large scale,multi-center,and longer-term follow-up clinical trials.