Composite bioabsorbable vascular stents via 3D bio-printing and electrospinning for treating stenotic vessels

A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method which combines 3D bio-printing and electrospinning to prepare the composite bioabsorbable vascular stent （CBVS） is proposed. The inner layer of the CBVS can be obtained through 3D bio- printing using poly-p-dioxanone （PPDO）. The thin nanofiber film that serves as the outer layer can be built through electrospinning using mixtures of chitosan-PVA （poly （vinyl alcohol））. Tests of mechanical properties show that the stent prepared through 3D bio-printing combined with electrospinning is better than that prepared through 3D bio- printing alone. Cells cultivated on the CBVS adhere and proliferate better due to the natural, biological chitosan in the outer layer. The proposed complex process and method can provide a good basis for preparing a controllable drug-carrying vascular stent. Overall, the CBVS can be a good candidate for treating stenotic vessels.

Potentially fatal haemobilia due to inappropriate use of an expanding biliary stent

AIM: To highlight the fatal complication caused by expanding biliary stents and the importance of avoiding use of expanding stent in potentially curable diseases.METHODS: Arteriobiliary fistula is an uncommon cause of haemobilia. We describe a case of right hepatic artery pseudoaneurysm causing arteriobiliary fistula and presenting as severe malena and cholangitis, in a patient with a mesh metal biliary stent. The patient had lymphoma causing bile duct obstruction.RESULTS: Gastroduodenoscopy failed to establish the exact source of bleeding and hepatic artery angiography and selective embolisation of the pseudo aneurysm successfully controlled the bleeding.CONCLUSION: Bleeding from the pseudo aneurysm of the hepatic artery can be fatal. Mesh metal stents in biliary tree can cause this complication as demonstrated in this case.So mesh metal stent insertion should be avoided in potentially benign or in curable conditions. Difficulty in diagnosis and management is discussed along with the review of the literature.

Comparison of different intervention procedures in benign stricture of gastrointestinal tract

AIM:To determine the most effective intervention procedure by evaluation of mid and long-term therapeutic efficacy in patients of stricture of the gastrointestinal tract (GTT). METHODS:Different intervention procedures were used to treat benign stricture of GIT in 180 patients including pneumatic dilation (group A,n=80),permanent (group B, n=25) and temporary (group C,n=75) placement of expandable metallic stents. RESULTS:The diameters of the strictured GIT were significantly greater after the treatment of all procedures employed (P<0.01).For the 80 patients in group A,160 dilations were performed (mean,2.0 times per patient). Complications in group A included chest pain (n=20),reflux (n=16),and bleeding (n=6).Dysphagia relapse occurred in 24(30%) and 48 (60%) patients respectively during 6-and- 12 momth follow-up periods in group A.In group B,25 uncovered or partially covered or antireflux covered expandable metallic stents were placed permantly, complications included chest pain (n=10),reflux (n=15), bleeding (n=3),and stent migration (n=4),and dysphagia relapse occurred in 5 (20%) and 3 patients (25%) during the 6-and-12 month follow-up periods,respectively.In group C,the partially covered expandable metallic stents were temporarily placed in 75 patients and removed after 3 to 7 days via gastroscope,complications including chest pain (n=30),reflux (n=9),and bleeding (n=12),and dysphagia relapse occurred in 9 (12%) and 8 patients (16%) during the 6-and-12 month follow-up periods,respectively.The placement and withdrawal of stents were all successfully performed.The follow-up of all patients lasted for 6 to 96 months (mean 45.3±18.6 months). CONCLUSION:The effective procedures for benign GIT stricture are pneumatic dilation and temporary placement of partially-covered expandable metallic stents.Temporary placement of partially-covered expandable metallic stents is one of the best methods for benign GIT strictures in mid and long-term therapeutic efficacy.

Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

AIM： To introduce and evaluate a new method to re- pair bile duct defect with a degradable stent and au- tologous tissues. METHODS： Eight Ba-Ma mini-pigs were used in this study, Experimental models with common bile duct （CBD） defect （0,5-1,0 cm segment of CBD resected） were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-（1,3-propanediol）-co- （1,2-propanediol）]. In addition, a vascularized greater omentum was placed around the stent and both ends of CBD. Cholangiography via gall bladder was per- formed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture. Complete blood count was examined pre- and post- operatively to estimate the inflammatory reaction. Liver enzymes and serum bilirubin were examined pre- and post-operatively to evaluate the liver function. Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis. The other three pigs were raised for one year for long-term observation. RESULTS： All the animals underwent surgery success- fully. There was no intraoperative mortality and no bile leakage during the observation period, The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation, the difference was not statistically significant （P = 0.652）. The plasma level of alanine aminotrans- ferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation （P = 0.810）. Nevertheless, the plasma level of y-glutamyl transferase was increased after opera- tion in both groups （P = 0.004）, especially 2 wk after operation. The level of serum total bilirubin after opera- tion was not significantly elevated compared with that before operation （P = 0.227）, so did the serum direct bilirubin （P = 0.759）. By cholangiography yia gall blad- der, we found that the stent maintained its integrity of shape and was stillin situ at month 1, and it disap- peared completely at month 3. No severe CBD dilation and stricture were observed at both months 1 and 3. No pig died during the 3-too postoperative observation period. No sign of necrosis, bile duct stricture, bile leak- age or abdominal abscess was found at reoperation at month 3 postoperatively. Pigs had neither fragments of stent nor stones formed in the CBD. Collagen deposit was observed in the anastomosis by hematoxylin and eosin （HE） and Masson＇s trichrome stains. No severe cholestasis was observed in liver parenchyma by HE staining. Intestinal obstruction was found in a pig 4 mo after operation, and no bile leakage, bile duct stricture or biliary obstruction were observed in laparotomy. No sign of bile duct stricture or bile leakage was observed in the other two pigs. CONCLUSION： The novel method for repairing bile duct defect yielded a good short-term effect without postoperative bile duct stricture. However, the long- term effect should be further studied.

Assessment of Coronary Stents by 64-slice Computed Tomography: In-stent Lumen Visibility and Patency

Objective To assess lumen visibility of coronary stents by 64-slice computed tomography （CT） coronary angiography, and determine the value of 64-slice CT in non-invasive detecting of in-stent restenosis after coronary artery stent implantation. Methods Totally, 60 patients （54 males, aged 57.0±12.7 years） and /05 stents were investigated by 64-slice CT at a mean interval of 20.0±16.6 months after coronary stents implantation. Axial multi-planar reconstruction images of the stents and curved-planar reconstruction images through the median of the stents were reconstructed for evaluating stent image quality on a 5-point scale （1=excellent, 5=nonassessable）, and stent lumen diameter was detected. Conventional coronary angiography was performed in 18 patients, and 32 stents were evaluated. Results Image quality was good to excellent on average （score 1.71±0.76）. Stent image quality score was correlated to heart rate （r=0. 281, P〈0.01） and stent diameter （r=-0.480, P〈0.001）. All the stents were assessable in lumen visibility with an average visible lumen diameter percentage of 60.7%±13.6%. Visible lumen diameter percentage was correlated to heart rate （r=-0.193, P〈0.05）, stent diameter （r=0.403, P〈0.001）, and stent image quality score （r=-0.500, P〈0.001）. Visible lumen diameter percentage also varied depending on the stent type. In comparison with the conventional coronary angiography, 4 of 6 in-stent stenoses were correctly detected. The sensitivity and specificity for the detection of in-stent stenosis were 66.7% and 84.6%, respectively. Conclusions Using a 64-slice CT, the stent lumen is partly visible in most of the stents. And 64-slice CT may be useful in the assessment of stent patency.

Vessel healings after stenting with different polymers in STEMI patients

Background Different stems implantation in ST-segmem elevation myocardial infarction （STEMI） patients may influence the long term prognosis by affecting vessel healings after stenting. The aim of this study was to evaluate the vessel healings after implantation of drug elming stems （DES） with biodegradable or durable polymer or of bare-metal stems （BMS） in patients with ache STEMI. Methods This study included 50 patients, who underwem follow up angiogram and optical coherence tomography （OCT） assessment about one year after percutaneous coronary intervemion （PCI） for STEMI. According to the initial stems types, these patients were classified to durable （n = 19） or biodegradable polymer sirolimus-eluting stems （n = 15）, or BMS （n = 16） groups. The conditions of stem struts coverage and malapposi- tion were analyzed with OCT technique. Results A total of 9003 struts were analyzed： 3299, 3202 and 2502 from durable or biodegradable polymer DES, or BMS, respectively. Strut coverage rate （89.0%, 94.9% and 99.3%, respectively）, malapposition presence （1.7%, 0.03% and 0 of struts, respectively） and average intimal thickness over struts （76 ± 12 μm, 161 ± 30 μm and 292 ± 29 μm, respectively） were significantly differem among different stent groups （all P 〈 0.001）. Conclusions Vessel healing status in STEMI patients is superior after implantation of biodegradable polymer DES than durable polymer DES, while both are inferior to BMS.

Study on in Vitro Degradation of Sutures for Decomposable Esophageal Stent

PLLA and PGLA sutures for decomposable esophageal stent were investigated in phosphate buffer solution （PBS） （pH=7.4） at 37 ℃ for a period of 8 weeks. In vitro degradation was studied by determining the change of weight loss, pH value, intrinsic viscosity, tensile strength, orientation degree, degree of crystallinity, melting point and surface morphology of the suture samples. The results showed that all properties of PLLA sutures had no obvious changes, however, the properties of PGLA sutures all changed significantly. The pH value, intrinsic viscosity, tensile strength, orientation degree and degree of crystallinity decreased gradually, and the weight loss of PGLA sutures increased with the degradation time. At 6th week, tensile strength of PGLA sutures nearly reached O, and weight loss approached to 70% at 8th week. The results of DSC showed that melting point of crystalline region of PGLA sutures substantially remained unchanged and melting heat enthalpy increased gradually during in vitro degradation, and the new ordered regions appeared in the amorphous area. The results of SEM showed that surface coating of PGLA sutures spalled initially, and then the sutures occured transverse rupture. Therefore, PGLA suture is suitable to prepare decomposable esophageal stent to expand benign esophageal stenosis or stricture, but stent prepared by PLLA suture is not appropriate for the treatment of benign esophageal stenosis because it is decomposed for more than 2 months.

用可溶性小管道内支架行输卵管复通术113例报告

本文报告113例应用可溶性小管道内支架行输卵管复通术.认为应用可溶性支架具有支架的支撑桥梁作用,使组织对合准确,防止缝合对侧壁及粘膜外翻.对组织无刺激、无损伤、可提高通畅率及受孕率.

Biodegradable magnesium implants:a potential scaffold for bone tumor patients

Relapse and metastasis of tumor may occur for osteosarcoma(OS)patients after clinical resection.Conventional metallic scaffolds provide sufficient mechanical support to the defected bone but fail to eradicate recurring tumors.Here we report that biodegradable magnesium(Mg)wirebased implant can inhibit OS growth.In brief,the Mg wires release Mg ions to activate the transport of zinc finger protein Snail1 from cytoplasm to cell nucleus,which induces apoptosis and inhibits proliferation of OS cells through a parallel antitumor signaling pathway of miRNA-181d-5p/TIMP3 and miRNA-181c-5p/NLK downstream.Simultaneously,the hydrogen gas evolution from Mg wires eliminates intracellular excessive reactive oxygen species,by which the growth of bone tumor cells is suppressed.The subcutaneous tumor-bearing experiment of OS cells in nude mice further confirms that Mg wires can effectively inhibit the growth of tumors and prolong the survival of tumor-bearing mice.In addition,Mg wires have no toxicity to normal cells and tissues.These results suggest that Mg implant is a potential anti-tumor scaffold for OS patients.

Delivering MC3T3-E1 cells into injectable calcium phosphate cement through alginate-chitosan microcapsules for bone tissue engineering

Objective： To deliver cells deep into injectable calcium phosphate cement（CPC） through alginate-chitosan（AC） microcapsules and investigate the biological behavior of the cells released from microcapsules into the CPC.Methods： Mouse osteoblastic MC3T3-E1 cells were embedded in alginate and AC microcapsules using an electrostatic droplet generator.The two types of cell-encapsulating microcapsules were then mixed with a CPC paste.MC3T3-E1 cell viability was investigated using a Wst-8 kit,and osteogenic differentiation was demonstrated by an alkaline phosphatase（ALP） activity assay.Cell attachment in CPC was observed by an environment scanning electron microscopy.Results： Both alginate and AC microcapsules were able to release the encapsulated MC3T3-E1 cells when mixed with CPC paste.The released cells attached to the setting CPC scaffolds,survived,differentiated,and formed mineralized nodules.Cells grew in the pores concomitantly created by the AC microcapsules in situ within the CPC.At Day 21,cellular ALP activity in the AC group was approximately four times that at Day 7 and exceeded that of the alginate microcapsule group（P0.05）.Pores formed by the AC microcapsules had a diameter of several hundred microns and were spherical compared with those formed by alginate microcapsules.Conclusions： AC microcapsule is a promising carrier to release seeding cells deep into an injectable CPC scaffold for bone engineering.

In vitro and in vivo cytocompatibility evaluation of biodegradable magnesium-based stents: a review

Biodegradable magnesium（Mg）-based vascular stents have been designed as temporary scaffolds to treat angiostenotic lesions for the maintenance of normal blood flow.Numerous studies have presented in vitro and in vivo tests for the evaluation of the safety and feasibility of Mg-based vascular stents and the related materials. Therein the cytocompatibility is a basic and important parameter in the evaluation system. In this review, we summarize the applications and limitations of in vitro evaluation methods including basic characterization methods and direct and indirect cytotoxicity tests. We discuss the influencing factors on cytotoxicity, such as surface roughness, preconditioning of sample surface, cell type for the biocompatibility evaluation in direct contact as well as conditions for the formation of extracts/degradation products for indirect assays. Besides, we highlight the recent in vivo animal tests and clinical trials about Mgbased stents along with some associated results. The aim of this review is to provide a meaningful reference in the further developments and related evaluation methods of Mg-based stents.

Whole meniscus regeneration using polymer scaffolds oaded with fibrochondrocytes

Objective： To study the feasibility of regenerating a whole menisci using poly-（3- hydroxybutyrate-co-3-hydroxyvalerate） （PHBV） scaffolds loaded with meniscal cells in rabbits undergoing total meniscectomy, and to explore its protective effect on carti- lage degeneration. Methods： A solvent casting and particulate leaching technique was employed to fabricate biodegradable PHBV scaffolds into a meniscal shape. The proliferated meniscal cells were seeded onto the polymer scaffolds, transplanted into rabbit knee joints whose lateral menisci had been removed. Eight to 18 weeks after transplantation, the rege- nerated neomenisci were evaluated by gross and histologi- cal observations. Cartilage Mankin score. degeneration was assessed by Results： Eighteen weeks after transplantation, the implants formed neomenisci. Hematoxylin and eosin （HE） staining of the neomenisci sections revealed regeneration of fibrocartilage. Type I collagen in the neomenisci was also proved similar to normal meniscal tissue by immunohis-tochemical analysis and Sirius scarlet trinitrophenol staining. Articular cartilage degeneration was observed 8 weeks af- ter implantation. It was less severe as compared with that in total meniscectomy controls and no further degeneration was observed at 18 weeks. At that time, the regenerated neomenisci strongly resembled normal meniscal fibrocarti- lage in gross and histological appearance, and its mechani- cal property was also close to that of normal meniscus. Conclusions： The present study demonstrates the feasibility of tissue-engineering a whole meniscal structure in total meniscectomy rabbit models using biodegradable PHBV scaffolds together with cultured allogeneic meniscal cells. Cartilage degeneration is decreased. But long-term in vivo investigations on the histological structure and cartilage degeneration of the neomenisci regenerated by this method are still necessary to determine the clinical potential of this tissue engineering avenue.