Biodegradable versus multiple plastic stent implantation in benign biliary strictures: A systematic review and meta-analysis.

PURPOSE: Benign biliary strictures arise mostly from iatrogenic injuries during surgical procedures and various inflammatory causes. Endoscopic placement of multiple plastic stents (MPS) is often regarded as the first-line therapy, albeit not without limitations. Biodegradable biliary stents (BDBS) present an alternative therapeutic option aimed at overcoming these shortcomings. The long-term stricture resolution rates between BDBS and MPS implantation in patients with benign biliary strictures (BBS) was therefore analyzed and compared, regardless of etiology. METHOD: Using predefined data fields, all articles published up to July 2018 were retrospectively selected and independently extracted by two authors and then excluded according to predefined criteria. Additional studies were identified by manually searching through article references. Any disagreements between authors on study selection were resolved by consensus. RESULTS: 3 studies for BDBS (n = 133) and 6 for MPS technique (n = 441) met the inclusion criteria. The overall success rate (defined as no stricture recurrence during follow-up) for BDBS implantation was 83 % (95 % [CI], 0.76-0.89), compared to 84 % (95 % [CI], 0.78-0.89) in the MPS group. Overall stent-related complication rates were reported to be slightly inferior in the BDBS group when compared to MPS, except for cholangitis (24.1 % vs. 6.1 %, respectively) and haemobilia (3% vs <1%, respectively). On average, BDBS required less interventions than MPS use (1 vs. 3, respectively). CONCLUSIONS: The insertion of BDBS in the treatment of benign biliary strictures does not seem to be inferior to multiple plastic stents in resolving and maintaining long-term biliary duct patency, albeit exhibiting higher rates of post-procedural cholangitis.

Five-year clinical efficacy and safety of contemporary thin-strut biodegradable polymer versus durable polymer drug-eluting stents: a systematic review and meta-analysis of 9 randomized controlled trials.

Very long-term data of the biodegradable polymer drug-eluting stents (BP-DES) in comparison with the contemporary durable polymer DES (DP-DES) are still to be investigated. We aimed to investigate the very long-term clinical performance of contemporary BP-DES against the DP-DES. We performed a systematic review to evaluate very long-term clinical outcomes of BP-DES versus DP-DES. Inclusion criteria were randomized design comparing BP-DES against DP-DES and follow-up duration ≥ 36 months. MEDLINE, EMBASE, and CENTRAL without restricting language or publication status were searched up to December 2018. The primary efficacy and safety endpoints were target lesion failure (TLF; a composite of cardiac death, target vessel myocardial infarction and ischemia-driven target lesion revascularization) and definite/probable stent thrombosis (ST), respectively. Primary analysis was done for the contemporary thin-strut BP- and DP-DES (strut thickness < 100 µm). A total of 9 trials comprising 10,699 patients (BP-DES, n = 6241 versus DP-DES, n = 4458) were analyzed. The mean follow-up duration was 63 months. No significant difference was found in TLF [Odds ratio (95% CI) 1.04 (0.89-1.21)] and definite/probable ST (odds ratio (95% CI) 0.78 (0.59-1.01)] between the BP- and DP-DESs. The present meta-analysis suggested that the contemporary thin-strut BP- and DP-DES have similar efficacy and safety profile at 5-year follow-up.Clinical trial registration PROSPERO; CRD42018101983 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=101983.

New Absorbable Microvascular Anastomotic Devices Representing a Modified Sleeve Technique: Evaluation of Two Types of Source Material and Design.

The purpose of this study was to create a new absorbable vascular anastomotic coupler and evaluate the patency and degradation degree. Vascular anastomosis was performed in the jugular vein in 31 New Zealand white female rabbits. The coupler consisted of an inner and outer ring. One side of the jugular vein was passed through and overlapped the inner ring. The opposite side of the jugular vein overlapped the everted jugular vein on the inner ring. Then, the outer ring engaged with the inner ring and completed the anastomosis. The outer rings were also constructed with two shapes including an O-type that had no slit and a C-type with a slit on the outer ring of the O-type coupler to allows expandability of the diameter. A Phase I experiment was performed to evaluate the degradability of the source materials, including the poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) couplers. A Phase II experiment was performed to evaluate the patency and anastomosis time of the O-type PLGA and PCL couplers. A Phase III experiment was performed to evaluate the patency and anastomosis time of suture anastomosis (control) and the C-type PLGA coupler. The patency was determined by ultrasonography and open exploration. Histological analysis was performed to determine the degradability of the couplers. In Phase I, the PLGA couplers were completely degraded with good vascular wall remodeling at 8 months, while the PCL couplers demonstrated incomplete degradation. In Phases II and III, the anastomosis time was significantly shorter in the coupler groups than that in the control group. All of the coupler groups demonstrated complete patency of the anastomoses on ultrasonography. In Phase III, the C-type PLGA coupler also demonstrated patency and complete degradation at 8 months. PLGA is a suitable source material for absorbable couplers due to its fast degradability. We devised the O-shaped outer ring for the C-shaped outer ring to increase flexibility, which also demonstrated complete patency during the experimental period. Our absorbable microvascular anastomosis devices could provide rapid and reliable microvascular anastomosis without anastomotic failure.

Biodegradable Magnesium-Incorporated Poly(l-lactic acid) Microspheres for Manipulation of Drug Release and Alleviation of Inflammatory Response.

Poly(l-lactic acid) (PLLA) and magnesium (Mg) are widely concerned biodegradable materials, but during in vivo implantation, the former produces acidic degradation byproducts and can easily induce inflammation in surrounding tissues, whereas the latter is fast corroded and generates alkaline products. The purpose of this study is to develop Mg/PLLA composite microspheres as a novel delivery system, in which Mg particles are used to regulate the drug release profile and suppress PLLA-induced inflammatory response. Morphological observation shows that multiple Mg particles are dispersed both on the surface and in the interior of composite microspheres. In vitro release study indicates that by varying the Mg contents or its particle sizes, the internal connectivity of composite microspheres is changed during hydrolytic degradation, and drug delivery can be facilely manipulated with tunable release patterns. In vivo release study further confirms the feasibility of Mg/PLLA microspheres for tailoring drug release in a physiological environment. The animal experiment reveals that Mg particles can alleviate macrophage infiltration and inflammatory cytokine expression. These results demonstrate the availability of using biodegradable Mg particles to manipulate drug release as well as alleviate PLLA-induced inflammation. The present Mg/PLLA composite microspheres have potential applications in controlled delivery of various therapeutic agents, especially some growth factors, for bone regeneration.

Internal surgical use of biodegradable carbohydrate polymers. Warning for a conscious and proper use of oxidized regenerated cellulose.

Oxidized regenerated cellulose has become a major local surgical hemostatic biomaterial because of its ease of use, favorable biocompatibility, bactericidal activity and bioabsorption characteristics. Additional clinical indications of oxidized regenerated cellulose include wound repair and tissue reconstruction. Sometimes, some unusual adverse events are described. Studies report cases of minor postoperative complications as nidus of infection or allergic reaction mainly presenting as acute dermatitis, eczema and sieroma. Also, rare and serious cases of foreign body reaction or impingement on nerve, due to not optimal bioabsorption, are showed in various surgical sites. Thus, on the one hand, patients should be informed by their clinicians of the possibility of these low incidence postoperative complications when considering preparations made of cellulose derivatives; and the clinicians should clearly indicate use of this biomaterial in the surgical procedure report so that radiologists may appropriately interpret any unusual findings potentially associated with this biomaterial use and thus avoid misdiagnosis and undue alarm in the follow-up of patients. On the other hand, the biomedical carbohydrate scientist must consider effective experimental design that substantially addresses the clinical adverse events associated with carbohydrate polymer use. Optimal development of carbohydrates for clinical use depends on excellent clinician/biomedical scientist communication.

Adverse effects of non-biodegradable and compostable plastic bags on the establishment of coastal dune vegetation: First experimental evidences.

Non-biodegradable and compostable plastic bags on beaches negatively affect the development of coastal dune vegetation by drastically reducing seedling emergence and growth.

Degradable and Injectable Hydrogel for Drug Delivery in Soft Tissues.

Injectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm- b-PLA- b-PEG- b-PLA- b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel formation at around 30 °C was demonstrated to be mediated by intermicellar bridging through the PEG central block. Such a result was particularly highlighted by the inability of a PEG- b-PLA- b-PNIPAAm triblock analog of the same composition to gelify. The hydrogels degraded through hydrolysis of the PLA esters until complete mass loss due to the diffusion of the recovered PEG and PNIPAAm/micelle based residues in the solution. Interestingly, hydrophobic molecules such as riluzole (neuroprotective drug) or cyanine 5.5 (imaging probe) could be easily loaded in the hydrogels' micelle cores by mixing them with the copolymer solution at room temperature. Drug release was correlated to polymer mass loss. The hydrogel was shown to be cytocompatible (neuronal cells, in vitro) and injectable through a small-gauge needle (in vivo in rats). Thus, this hydrogel platform displays highly attractive features for use in brain/soft tissue engineering as well as in drug delivery.

A pH- and temperature-responsive bioresorbable injectable hydrogel based on polypeptide block copolymers for the sustained delivery of proteins in vivo.

Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive in situ-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining N-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using N-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 µg mL-1). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The in vivo gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel in vivo and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.

Safety and durability of the biodegradable felt in aortic surgery: a propensity score-matched study.

OBJECTIVES: Suture line disruption is a serious complication after aortic surgery. We previously reported in a canine model that basic fibroblast growth factor-incorporated biodegradable polyglycolic acid (PGA) felt prevented tissue derangement at the anastomotic site. This study sought to evaluate the safety and durability of this biodegradable felt. METHODS: Between January 2007 and December 2011, 67 patients who consented to undergo aortic surgery with the basic fibroblast growth factor-incorporated PGA felt were enrolled (Group P). As a control, we retrospectively reviewed the charts of 129 patients who underwent aortic surgery using a polytetrafluoroethylene felt during the same registration period (Group N). On the basis of 18 preoperative covariates, 60 well-matched patient pairs were identified using propensity matching, and their clinical indices were compared. RESULTS: Among the matched pairs, in-hospital mortality and postoperative complication rates did not statistically differ between the groups. During a median follow-up of 4.8 years, the rate of anastomotic aneurysm was 1.7% (1 patient) in both groups. The rates of overall survival and freedom from aortic events did not differ between the groups. In total, 65 anastomoses in Group P and 54 anastomoses in Group N were monitored via computed tomography, and the diameters of the juxta-anastomotic sites in Group N were more likely to be increased than those in Group P {dilatation ratio [(post-discharge diameter - predischarge diameter)/predischarge diameter × 100 (%)]: 4.3% ± 0.6% vs 2.5% ± 0.5%, P = 0.01}. CONCLUSIONS: The basic fibroblast growth factor-incorporated PGA felt was as safe and durable as conventional felt for reinforcement in aortic surgery. The attenuation of juxta-anastomotic aortic dilatation by PGA felt reinforcement may provide more beneficial effects on long-term outcomes.

Biodegradable plastic bags on the seafloor: A future threat for seagrass meadows?

Marine plastic litter is a global concern. Carrier bags manufactured from non-biodegradable polymers constitute a large component of this litter. Because of their adverse impact on marine life, non-biodegradable bags have recently been replaced by biodegradable ones. However, growing evidence shows that these latter are not readily degradable in marine sediments and can alter benthic assemblages. The potential impact of biodegradable bags on seagrasses inhabiting sandy bottoms, which are the most widespread and productive ecosystems of the coastal zones, has been ignored. Mesocosm experiments were conducted to assess the effect of a commercialized biodegradable bag on a common seagrass species of the Mediterranean, Cymodocea nodosa, both at the level of individual plant (clonal growth) and of plant community (plant-plant relationships), under three culture regimes (plant alone, in combination with a neighbour of the same species or of the co-existing seagrass Zostera noltei) simulating different natural conditions (bare substrate, monospecific meadows or mixed meadows). The bag behaviour in marine sediment and sediment physical/chemical variables were also examined. After six months of sediment exposure, the bag retained considerable mass (85% initial weight) and reduced sediment pore-water oxygen concentration and pH. In the presence of bag, C. nodosa root spread and vegetative recruitment increased compared to controls, both intra- and interspecific interactions shifted from neutral to competitive, and the growth form changed from guerrilla (loosely arranged group of widely spaced ramets) to phalanx form (compact structure of closed spaced ramets) but only with Z. noltei. These findings suggest that biodegradable bags altering sediment geochemistry could promote the spatial segregation of seagrass clones and influence species coexistence.

Preparation of Biodegradable and Elastic Poly(ε-caprolactone-co-lactide) Copolymers and Evaluation as a Localized and Sustained Drug Delivery Carrier.

To develop a biodegradable polymer possessing elasticity and flexibility, we synthesized MPEG-b-(PCL-co-PLA) copolymers (PCxLyA), which display specific rates of flexibility and elasticity. We synthesize the PCxLyA copolymers by ring-opening polymerization of ε-caprolactone and l-lactide. PCxLyA copolymers of various compositions were synthesized with 500,000 molecular weight. The PCxLyA copolymers mechanical properties were dependent on the mole ratio of the ε-caprolactone and l-lactide components. Cyclic tensile tests were carried out to investigate the resistance to creep of PCxLyA specimens after up to 20 deformation cycles to 50% elongation. After in vivo implantation, the PCxLyA implants exhibited biocompatibility, and gradually biodegraded over an eight-week experimental period. Immunohistochemical characterization showed that the PCxLyA implants provoked in vivo inflammation, which gradually decreased over time. The copolymer was used as a drug carrier for locally implantable drugs, the hydrophobic drug dexamethasone (Dex), and the water-soluble drug dexamethasone 21-phosphate disodium salt (Dex(p)). We monitored drug-loaded PCxLyA films for in vitro and in vivo drug release over 40 days and observed real-time sustained release of near-infrared (NIR) fluorescence over an extended period from hydrophobic IR-780- and hydrophilic IR-783-loaded PCxLyA implanted in live animals. Finally, we confirmed that PCxLyA films are usable as biodegradable, elastic drug carriers.

Design and evaluation of antibiotic releasing self- assembled scaffolds at room temperature using biodegradable polymer particles.

Biodegradable polymer-based drug-eluting implants offer many advantages such as predictable drug release kinetics, safety, and acceptable drug loading under ambient conditions. Herein, we describe fabrication and evaluation of antibiotic loaded scaffolds for localized delivery and tissue engineering applications. PDLLA particles entrapping gentamycin were formulated using solvent evaporation method and used for scaffold fabrication. Optimization of formulation parameters such as pH of the internal aqueous phase and combination of excipients like glycerol, polyvinyl alcohol (PVA) resulted in high entrapment efficiencies up to 96% of gentamicin in particles with drug load of 16-18µg/mg of polymer particles. These microparticles were fused in presence of methanol at ambient temperatures to form scaffolds of different geometry having reasonable mechanical strength. Porosity of these scaffolds was found to be more than 80%. Antibiotic released from the scaffolds was found to be bioactive as tested against Staphylococcus aureus and the release pattern was biphasic over a period of one week. The scaffolds were found to be non-toxic to murine fibroblasts cultures in vitro as well as to mice upon subcutaneous implantation. This method provides a novel and easy way of fabricating antibiotic loaded polymer scaffolds for varieties of applications.

The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence.

The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES.

Treatment of critically sized femoral defects with recombinant BMP-2 delivered by a modified mPEG-PLGA biodegradable thermosensitive hydrogel.

BACKGROUND: Reconstruction of a segmental fracture with massive bone loss is still a challenge for orthopaedic surgeons. The aim of our study was to develop a suitable biodegradable thermosensitive hydrogel system as a carrier for bone morphogenetic protein (BMP)-2 delivery in the treatment of critical-sized femoral defects. METHODS: A block copolymer composed of monomethoxypoly(ethylene glycol) (mPEG), poly(lactic-co-glycolic acid) (PLGA) and 2, 2'-Bis (2-oxazolin) (Box) was synthesized by ring opening polymerization. The synthesized block copolymer was characterized by (1)H-NMR spectroscopy and gel permeation chromatography (GPC). Different biophysical and biochemical properties of the synthesized copolymer, including temperature-induced structure changes, degradation rate, pH changes during hydrolytic degradation, cell toxicity, and the release profile of BMP-2, were also evaluated and/or were compared with those of a well-characterized mPEG-PLGA copolymer. In animal testing, rabbits (n = 36) that received critically sized (10 mm) femoral defects were divided into 6 groups. These experimental groups included an untreated group, autograft, and groups treated with the synthesized copolymer carrying different concentrations of BMP-2 (0, 5, 10, and 20 µg/ml). Bone repair was evaluated using X-ray radiography, histological staining, micro-computed tomography (µCT), biomarker examination and biomechanical testing in a 12-week treatment period. RESULTS: A new thermosensitive mPEG-PLGA/Box/mPEG-PLGA block copolymer, or named as BOX copolymer, was successfully prepared. Compared to the reported mPEG-PLGA in vitro, the prepared BOX copolymer at the same weight percent concentrations exhibited wider temperature ranges of gelation, slower degradation rates, higher the pH values, as well as less cytotoxicity. Furthermore, the BMP-2 release from BOX hydrogel exhibited a near-linear release profile in vitro. In animal experiments, treatment of critical-sized bony defects with 25 wt% BOX hydrogel carrying BMP-2 effectively promoted fracture healing during the 12-week trial period and higher concentrations of BMP-2 treatment correlated with better bone quality. Most importantly, clinical outcome and bone healing in the BOX-hydrogel group with 20 µg/ml BMP-2 were nearly equivalent to those in the autograft group in a 12-week treatment course. CONCLUSION: These data support that the use of BOX hydrogel (25 wt%) as a drug delivery system is a promising method in the treatment of large bone defects.

Facile Synthesis of Reductively Degradable Biopolymers Using Cystamine Diisocyanate as a Coupling Agent.

Reductively degradable biopolymers have emerged as a unique class of smart biomedical materials. Here, a functional coupling agent, cystamine diisocyanate (CDI), was designed to offer a facile access to reductively degradable biopolymers via polycondensation with various diols. CDI was readily obtained with a decent yield of 46% by reacting cystamine dihydrochloride with triphosgene. The polycondensation of oligo(ethylene glycol) diol (Mn = 0.4 or 1.5 kg/mol) or oligo(ε-caprolactone) diol (Mn = 0.53 kg/mol) with CDI in N,N-dimethylformamide at 60 °C using dibutyltin dilaurate as a catalyst afforded reductively degradable poly(ethylene glycol) (SSPEG, Mn = 6.2-76.8 kg/mol) or poly(ε-caprolactone) (SSPCL, Mn = 6.8-16.3 kg/mol), in which molecular weights were well controlled by diol/CDI molar ratios. Moreover, PEG-SSPCL-PEG triblock copolymers could be readily prepared by reacting dihydroxyl-terminated SSPCL with PEG-isocyanate derivative. PEG-SSPCL-PEG with an Mn of 5.0-16.3-5.0 kg/mol formed small-sized micelles with an average diameter of about 85 nm in PB buffer. The in vitro release studies using doxorubicin (DOX) as a model drug showed that, in sharp contrast to reduction-insensitive PEG-PCL(HDI)-PEG controls, drug release from PEG-SSPCL-PEG micelles was fast and nearly complete in 24 h under a reductive condition containing 10 mM glutathione. The confocal microscopy experiments in drug-resistant MCF-7 cells (MCF-7/ADR) displayed efficient cytoplasmic DOX release from PEG-SSPCL-PEG micelles. MTT assays revealed that DOX-loaded PEG-SSPCL-PEG micelles were much more potent against MCF-7/ADR cells than reduction-insensitive PEG-PCL(HDI)-PEG controls (IC50: 6.3 vs 55.4 µg/mL). It should further be noted that blank PEG-SSPCL-PEG micelles were noncytotoxic up to a tested concentration of 1 mg/mL. Hence, cystamine diisocyanate appears to be an innovative coupling agent that facilitates versatile synthesis of biocompatible and reductively degradable biopolymers.

Impacts of ridge-furrow rainfall concentration systems and mulches on corn growth and yield in the semiarid region of China.

BACKGROUND: Plastic-covered ridge-furrow farming systems for rainfall concentration (RC) improve the water availability for crops and increase the water use efficiency (WUE), thereby stabilizing high yields. In this study, we optimized the mulching patterns for RC planting to mitigate the risks of drought during crop production in semiarid agricultural areas. We conducted a 4-year field study to determine the RC effects on corn production of mulching in furrows with 8% biodegradable films (RCSB ), liquid film (RCSL ), bare furrow (RCSN ) and conventional flat (CF) farming. RESULTS: We found that RC significantly (P > 0.05) increased the soil moisture in the top 0-100 cm layer and the topsoil temperature (0-20 cm) during the corn-growing period. Mulching with different materials in planting furrows further improved the rain-harvesting, moisture-retaining and yield-increasing effects of RC planting. Compared with CF, the 4-year average total dry matter amount per plant for RCSB , RCSL and RCSN treatments increased by 42.1%, 30.8% and 17.2%, respectively. The grain yield increased by 59.7%, 53.4% and 32.6%, respectively. CONCLUSION: Plastic-covered ridge and furrow mulched with biodegradable film and liquid film is recommended for use in the semiarid Loess Plateau of China to alleviate the effects of drought on crop production. © 2015 Society of Chemical Industry.

Cell engineering by the internalization of bioinstructive micelles for enhanced bone regeneration.

AIM: To direct precursor cells toward the osteoblastic lineage, by using an intracellular nanocarrier releasing dexamethasone. MATERIALS & METHODS: Biodegradable gelatin-based micelles entrapped dexamethasone (dex-micelles). Internalization efficiency and biocompatibility of dex-micelles and their potency for in vitro osteogenic differentiation and in vivo bone regeneration were assessed. RESULTS: Dex-micelles were internalized by rat bone marrow mesenchymal stem cells and demonstrated a pH-responsive release profile and an enhancement of 2D and 3D in vitro osteogenic differentiation. In vivo implantation of gelatin scaffolds seeded with rat bone marrow mesenchymal stem cells precultured for 24 h with dex-micelles promoted a significant enhancement of de novo bone formation in a rat ulna defect, in a dose-dependent manner. CONCLUSION: The proposed intracellular delivery system is a powerful tool to promote bone regeneration.

Safety and efficacy of biodegradable drug-eluting vs. bare metal stents: a meta-analysis from randomized trials.

BACKGROUND: Biodegradable polymeric coatings have been proposed as a promising strategy to enhance biocompatibility and improve the delayed healing in the vessel. However, the efficacy and safety of biodegradable polymer drug-eluting stents (BP-DES) vs. bare metal stents (BMS) are unknown. The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of BP-DES vs. BMS. METHODS AND RESULTS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until December 2013, that compared any of approved BP-DES and BMS. Efficacy endpoints were target-vessel revascularization (TVR), target-lesion revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were death, myocardial infarction (MI), definite stent thrombosis (DST). The meta-analysis included 7 RCTs with 2,409 patients. As compared with BMS, there was a significantly reduced TVR (OR [95% CI] = 0.37 [0.28-0.50]), ISLL (OR [95% CI] = -0.41 [-0.48-0.34]) and TLR (OR [95% CI] = 0.38 [0.27-0.52]) in BP-DES patients. However, there were no difference for safety outcomes between BP-DES and BMS. CONCLUSIONS: BP-DES is more effective in reducing ISLL, TVR and TLR, as safe as standard BMS with regard to death, ST and MI. Further large RCTs with long-term follow-up are warranted to better define the relative merits of BP-DES.

In situ floating hydrogel for intravesical delivery of adriamycin without blocking urinary tract.

Drug solution is commonly used in conventional intravesical instillation. However, most of them would be easily eliminated by voiding, which significantly limit their efficacy. Recent advances in intravesical drug delivery are to use hydrogels as drug reservoir to extend the drug residence time in bladder. However, because of the high viscosity of hydrogel, urinary obstruction is usually existed during the intravesical instillation. To overcome these, we developed a floating hydrogel for the delivery of Adriamycin (ADR). The floating hydrogel was made of ADR, thermosensitive polymer (Poloxamer 407) and NaHCO3, which was liquid at low temperature, whereas formed gel at high temperature. In the presence of H⁺, NaHCO3 decomposed and produced CO2 that attached on the surface of hydrogel and helped the hydrogel float on the urine. Hence, the urinary tract will not be blocked. Meanwhile, the encapsulated ADR released in a controlled manner. These results suggest that the floating gel may have promising applications in intravesical therapy for bladder cancer.