Yueqi Zhu

A highly flexible paclitaxel-loaded poly(ε-caprolactone) electrospun fibrous-membrane-covered stent for benign cardia stricture.

In benign esophageal strictures, inflammation reaction and tissue hyperplasia after stent placement greatly limit the stent retention time and affect subsequent scar formation, which is one of the main influences on long-term recurrence rate. A newly developed biodegradable electrospun drug-fiber-coated stent (DFCS) was fabricated to inhibit inflammation and scar formation. The electrospun paclitaxel/poly(ε-caprolactone) (PCL) fibers integrally covered the bare stent using the rotating collection method. The paclitaxel entrapment did not significantly affect the physical properties of electrospun PCL fibrous membranes. The mechanical results demonstrated that electrospun fibers containing paclitaxel covering the stent maintained the original mechanical characteristics of the stent, and no membrane tearing or ablation was observed after hundreds of repeated compressions. Paclitaxel release profiles were controlled mainly via diffusion of drug through the drug content, and stable release of paclitaxel continued up to 32 days at pH 4.0. Higher inhibition of smooth muscle cell proliferation rates was observed on fibrous membranes with higher paclitaxel content. DFCS showed a significant decrease in tissue inflammation and collagen fiber proliferation, and was easily removed from the esophageal part, which had almost no damage to the tissues in the dog model. Therefore, DFCSs may have great potential to markedly attenuate stent-induced inflammation and scar formation in esophageal stenosis therapy.

Self-coated interfacial layer at organic/inorganic phase for temporally controlling dual-drug delivery from electrospun fibers.

Implantable tissue engineering scaffolds with temporally programmable multi-drug release are recognized as promising tools to improve therapeutic effects. A good example would be one that exhibits initial anti-inflammatory and long-term anti-tumor activities after tumor resection. In this study, a new strategy for self-coated interfacial layer on drug-loaded mesoporous silica nanoparticles (MSNs) based on mussel-mimetic catecholamine polymer (polydopamine, PDA) layer was developed between inorganic and organic matrix for controlling drug release. When the interface PDA coated MSNs were encapsulated in electrospun poly(L-lactide) (PLLA) fibers, the release rates of drugs located inside/outside the interfacial layer could be finely controlled, with short-term release of anti-inflammation ibuprofen (IBU) for 30 days in absence of interfacial interactions and sustained long-term release of doxorubicin (DOX) for 90 days in presence of interfacial interactions to inhibit potential tumor recurrence. The DOX@MSN-PDA/IBU/PLLA hybrid fibrous scaffolds were further found to inhibit proliferation of inflammatory macrophages and cancerous HeLa cells, while supporting the normal stromal fibroblast adhesion and proliferation at different release stages. These results have suggested that the interfacial obstruction layer at the organic/inorganic phase was able to control the release of drugs inside (slow)/outside (rapid) the interfacial layer in a programmable manner. We believe such interface polymer strategy will find applications in where temporally controlled multi-drug delivery is needed.

Synergistic mediation of tumor signaling pathways in hepatocellular carcinoma therapy via dual-drug-loaded pH-responsive electrospun fibrous scaffolds

With the understanding of tumorigenesis, the tumor-infiltrating inflammatory cells, which could contribute to carcinogenesis, have greatly drawn public attention. We hypothesized that controlling inflammation in the initial stage along with antitumor activity for a relatively long term could prevent tumor recurrence. Herein, we designed a novel electrospun composite poly(l-lactide) (PLLA) fibrous scaffold, which contained sodium bicarbonate (SB) and doxorubicin (DOX) inside mesoporous silica particles (MSNs) to achieve long-term pH-sensitive DOX release and ibuprofen (IBU) outside MSNs to achieve initial short-term release. This construct was found to exhibit an initial burst release of IBU at an early stage and sustained the release of DOX at a relatively later stage. In vivo results showed that when the fibrous scaffold was implanted in a liver-tumor-bearing nude mouse, the mouse lifespan was prolonged to 1.5 times higher than that when implanted with scaffolds with no IBU or SB. Moreover, the residual tumor treated with PLLA-(MSN/DOX-SB)-IBU fibers demonstrated considerable signs of apoptosis and large areas of necrosis over a 10 week examination period. By combining the in vitro and in vivo experiments, the results have suggested that this dual drug delivery system could effectively inhibit inflammation in the initial stage and prevent tumor recurrence for a relatively long term, and it may find application as a local implantable scaffold to treat a tissue defect after tumor resection.

Fabrication of a Delaying Biodegradable Magnesium Alloy-Based Esophageal Stent via Coating Elastic Polymer

Esophageal stent implantation can relieve esophageal stenosis and obstructions in benign esophageal strictures, and magnesium alloy stents are a good candidate because of biodegradation and biological safety. However, biodegradable esophageal stents show a poor corrosion resistance and a quick loss of mechanical support in vivo. In this study, we chose the elastic and biodegradable mixed polymer of Poly(ε-caprolactone) (PCL) and poly(trimethylene carbonate) (PTMC) as the coated membrane on magnesium alloy stents for fabricating a fully biodegradable esophageal stent, which showed an ability to delay the degradation time and maintain mechanical performance in the long term. After 48 repeated compressions, the mechanical testing demonstrated that the PCL-PTMC-coated magnesium stents possess good flexibility and elasticity, and could provide enough support against lesion compression when used in vivo. According to the in vitro degradation evaluation, the PCL-PTMC membrane coated on magnesium was a good material combination for biodegradable stents. During the in vivo evaluation, the proliferation of the smooth muscle cells showed no signs of cell toxicity. Histological examination revealed the inflammation scores at four weeks in the magnesium-(PCL-PTMC) stent group were similar to those in the control group (p > 0.05). The α-smooth muscle actin layer in the media was thinner in the magnesium-(PCL-PTMC) stent group than in the control group (p < 0.05). Both the epithelial and smooth muscle cell layers were significantly thinner in the magnesium-(PCL-PTMC) stent group than in the control group. The stent insertion was feasible and provided reliable support for at least four weeks, without causing severe injury or collagen deposition. Thus, this stent provides a new stent for the treatment of benign esophageal stricture and a novel research path in the development of temporary stents in other cases of benign stricture.

In vitro and in vivo evaluation of Rapamycin-eluting nanofibers coated on cardia stents

It is known that a Rapamycin (Rapa)-coating on stents can be potentially applied to treat benign cardia stricture, it is, however, difficult to use as a delivery system for controlled and sustained release particularly in an acidic environment. The aim of this study was therefore to explore the potential of self-expandable metal stents covered with Rapa-loaded electrospun poly(e-caprolactone) (PCL) fiber membranes for controlled Rapa delivery to inhibit inflammation and tissue hyperplasia. It was found that stents coated with the membranes had comparable mechanical properties including expansion properties, mechanical strength and rigidity with bare cardia stents. In addition, Rapa was found to be released from the membrane coated stents in a controlled and sustained manner, and via varying the concentration of Rapa incorporated in the PCL membranes, the drug release rates could be controlled. The released Rapa was also found to inhibit the proliferation of smooth muscle cells. Moreover, the site implanted with the stents coated with the Rapa loaded PCL membranes showed reduced tissue inflammation and collagen fiber deposition compared to those with no coating. The above results have therefore suggested that the new Rapa-coated stents developed in this study have great potential to treat benign cardia strictures.

Morphological characteristics of chronic total occlusion: predictors of different strategies for long-segment femoral arterial occlusions

ObjectivesTo investigate morphological characteristics used to predict recanalisation strategies in long-segment (>10 cm) femoral chronic total occlusion (LSF-CTO) angioplasty.MethodsWe retrospectively evaluated a range of morphological CTA and DSA features in patients who underwent recanalisation of LSF-CTO. The stage of CTO was classified into early (3–12 months) and late (>12 months) according to estimated duration. Characteristics including stump morphology, lesion length and calcification, proximal side branches, collaterals circulation, runoff vessels and concomitant arterial occlusion were used as predictors, and multivariate logistic regression analysis was performed to identify variables associated with late-stage CTO and retrograde technique.ResultsA total of 119 patients with 137 CTOs in 137 limbs were enrolled. Overall, successful recanalisation was achieved in 122 CTOs (89.1%). Flush occlusion [odds ratio (OR) 2.958; 95% confidence interval (CI) 1.172–7.465; p = 0.022], large collateral (OR 2.778; 95% CI 1.201–6.427; p = 0.017) and TransAtlantic Inter-Society Consensus II class D (TASC D) lesion (OR 1.743; 95% CI 1.019–2.981; p = 0.042) were predictors for late-stage CTO. Flush occlusion (OR 75.278; 95% CI 10.664–531.384; p < 0.001) and large collateral (OR 23.213; 95% CI 3.236–166.523; p = 0.002) were associated with high likelihood for retrograde approach.ConclusionsFlush occlusion and large collateral were associated with a CTO at late-stage which may require retrograde recanalisation.Key points• CTO morphological characteristics help estimate lesion duration and optimise recanalisation strategies.• Flush occlusion and large collateral is associated with late-stage CTO and retrograde recanalisation.• Application of anterograde and retrograde recanalisation for long-segment femoral CTO is effective.The original version of this article unfortunately contained mistakes. The legends to Figs. 2–4 were incorrectly interchanged. The correct versions are given below. The original article has been corrected.

Silicone-covered biodegradable magnesium- stent insertion in the esophagus: a comparison with plastic stents

Background: We determined the feasibility of, and tissue response to silicone-covered biodegradable magnesium- and plastic-stent insertion into the esophagus in rabbits. Methods: The mechanical compression–recovery characteristics and degradation behaviors of the magnesium stent were investigated in vitro. A total of 45 rabbits were randomly divided into a magnesium- (n = 15) and a plastic- (n = 15) stent group, and underwent stent insertion into the lower third of the esophagus under fluoroscopic guidance; a control group (n = 15) did not undergo the intervention. Esophagography was performed at 1, 2, and 4 weeks. Five rabbits in each group were euthanized at each time point for histological examination. Results: Silicone-covered magnesium stents showed similar radial force to plastic stents (p > 0.05). The magnesium stents degraded rapidly in an acidic solution, but 90.2% ± 3.1% of the residual mass was maintained after a 2-week degradation in a solution with a pH of 4.0. All stent insertions were well tolerated. Magnesium stents migrated in six rabbits (one at 1 week, one at 2 weeks and four at 4 weeks), and plastic stents migrated in three rabbits (one at 2 weeks and two at 4 weeks; p > 0.05). Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was similar in both stented groups (p > 0.05), and the esophagus wall was found to be significantly thinner in the stented groups than in the control group (p < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ from the control group (p > 0.05). Conclusions: Esophageal silicone-covered magnesium stents provided reliable support for at least 2 weeks, with acceptable migration rates and without causing severe injury or tissue reaction compared with plastic stents.

Fabrication and evaluation of polymer-based esophageal stents for benign esophagus stricture insertion

In benign esophageal strictures, an esophageal stent implantation can relieve esophageal lesions caused by esophageal stenosis and obstruction. However, the removal of metallic stents is difficult and biodegradable polymer stents show poor mechanical properties. In this study, polypropylene (PP) lines as skeleton fibers and silicone coating membranes were chosen to knit an esophageal stent for improved structural strength and easy removal. Mechanical testing demonstrated that the stent maintained its original mechanical characteristics after two hundred repeated compressions and pulls. According to a finite element simulation analysis of the stent, the left and right sides had higher stress concentrations than the loading contact site and the restraint site of both ends. The proliferation of smooth muscle cells showed no signs of cell toxicity. During an in vivo evaluation, the changes to the esophageal wall were significant: thinner epithelial and smooth muscle actin layers in the PP–silicone stent group than in the control group (P 0.05). The esophageal PP–silicone stent insertion was feasible and provided reliable support for at least 4 weeks, with acceptable migration rates and without causing severe injury or collagen deposition. Therefore PP stents have great potential to provide a new method and practical basis for the treatment of benign esophageal strictures.

Efficacy and safety evaluation of paclitaxel-loaded metal stents in patients with malignant biliary obstructions

Paclitaxel-eluting covered metal stents (PECMSs) and metallic stents covered with a paclitaxel-incorporated membrane (MSCPMs) have been developed to increase stent patency by preventing tumor ingrowth. However, few studies have compared their efficacy and safety compared with conventional covered metal stents (CMSs). This study aimed to compare differences in efficacy and safety between PECMS/MSCPM and CMS by meta-analysis. A search of PubMed and Embase was conducted for randomized controlled trials of PECMS/MSCPM and CMS in patients with malignant biliary obstructions published between January 1966 and August 2017. A meta-analysis was performed to compare clinical outcomes and complications between stent types. A total of 221 patients from three studies were included. There were no significant differences between PECMS/MSCPM and CMS in stent patency duration (P = 0.128) or survival time (P = 0.363). Risk did not differ between PECMS/MSCPM and CMS for stent malfunction (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.63-2.02, P = 0.677 for all stent malfunction; HR: 1.39, 95% CI: 0.68-2.85, P = 0.362 for stent occlusion caused by tumor ingrowth; HR: 0.80, 95% CI: 0.34-1.91, P = 0.617 for stent occlusion caused by distal stent migration or sludge impaction), or complications (HR: 1.54, 95% CI: 0.70-3.39, P = 0.280 for all complications; HR: 0.42, 95% CI: 0.14-1.30, P = 0.131 for pancreatitis). The exception was cholangitis-like symptoms, the risk for which was higher in PECMS/MSCPM compared with CMS (HR: 3.93, 95% CI: 1.08-14.29, P = 0.038). Although PECMS/MSCPM may be associated with higher risk of cholangitis-like symptoms, the overall results were similar between PECMS/MSCPM and CMS. Further studies are warranted in larger populations of patients.