Study In Vivo Intraocular Biocompatibility of In Situ Gelation Hydrogels: Poly(2-Ethyl Oxazoline)-Block-Poly(ε-Caprolactone)-Block-Poly(2-Ethyl Oxazoline) Copolymer,Matrigel and Pluronic F127

The long term in vivo biocompatibility is an essential feature for the design and development of sustained drug release carriers. In the recent intraocular drug delivery studies, hydrogels were suggested as sustained release carriers. The biocompatibility test for these hydrogels, however, was commonly performed only through in vitro cell culture examination, which is insufficient before the clinical applications. We compared three thermosensitive hydrogels that have been suggested as the carriers for drugs by their gel-solution phase-change properties. A new block terpolymer (PEOz-PCL-PEOz, ECE) and two commercial products (Matrigel® and Pluronic F127) were studied. The results demonstrated that the ocular media remained translucent for ECE and Pluronic F127 in the first 2 weeks, but cataract formation for Matrigel occurred in 2 weeks and for Pluronic F127 in 1 month, while turbid media was observed for both Matrigel and Pluronic F127 in 2 months. The electrophysiology examinations showed significant neuroretinal toxicity of Matrigel and Pluronic F127 but good biocompatibility of ECE. The neuroretinal toxicity of Matrigel and Pluronic F127 and superior biocompatibility of ECE hydrogel suggests ECE as more appropriate biomaterial for use in research and potentially in intraocular application.     

Fabrication of multiresponsive shell cross-linked micelles possessing pH-controllable core swellability and thermo-tunable corona permeability

A double hydrophilic ABC triblock copolymer, poly(2-(diethylamino)ethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(N-isopropylacrylamide) (PDEA-b-PDMA-b-PNIPAM), containing the well-known pH-responsive PDEA block and thermoresponsive PNIPAM block, was synthesized by atom transfer radical polymerization via sequential monomer addition using ethyl 2-chloropropionate as the initiator. The obtained triblock copolymer exhibits interesting "schizophrenic" micellization behavior in aqueous solution, and supramolecularly self-assembles into three-layer "onion-like" PNIPAM-core micelles at acidic pH's and elevated temperatures and PDEA-core micelles with "inverted" structures at alkaline pH's and room temperature. In both cases, dynamic laser light scattering (LLS) and optical transmittance reveal the presence of near-monodisperse micelles, and the micelle formation/inversion process is fully reversible. Novel shell cross-linked (SCL) micelles with pH-responsive PDEA cores and thermoresponsive PNIPAM coronas were then facilely fabricated from the PDEA-b-PDMA-b-PNIPAM triblock copolymer by cross-linking the PDMA inner shells with 1,2-bis(2-iodoethoxy)ethane. The reversible pH-dependent swelling/shrinking of PDEA cores and thermosensitive collapse/aggregation of PNIPAM coronas of the obtained SCL micelles were investigated in detail by dynamic LLS, optical transmittance, and transmission electron microscopy. As the structurally stable SCL micelles possess pH-controllable core swellability and thermo-tunable corona permeability, the release profile of a model hydrophobic drug, dipyridamole, initially loaded within the hydrophobic PDEA core, can be dually controlled by both the solution pH and the temperature. This represents the first report of SCL micelles with multiresponsive cores and coronas, which may find practical applications in fields such as drug delivery and smart release.     

Injectable Supramolecular Hydrogel from Insulin-Loaded Triblock PCL-PEG-PCL Copolymer and γ-Cyclodextrin with Sustained-Release Property

Supramolecular hydrogels formed by cyclodextrins and polymers have been widely investigated as a biocompatible, biodegradable and controllable drug delivery system. In this study, a supramolecular hydrogel based on biodegradable poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL-PEG-PCL) triblock copolymers and γ-cyclodextrin (γ-CD) was prepared through inclusion complexation as an injectable, sustained-release vehicle for insulin. The triblock copolymer PCL-PEG-PCL was synthesised by the ring-opening polymerisation method, using microwave irradiation. The polymerisation reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The supramolecular hydrogel was prepared in aqueous solution by blending an aqueous γ-CD solution with an aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. In vitro insulin release through the hydrogel system was studied. The relative surface hydrophobicity of standard and released insulin from the SMGel was estimated using 8-anilino-1-naphthalene sulfonic acid (ANS). Results of ¹HNMR and gel permeation chromatography revealed that microwave irradiation is a simple and reliable method for synthesis of PCL-PEG-PCL copolymer. Gelation occurred within a minute. The supramolecular hydrogel obtained by mixing 10.54% (w/v) γ-CD and 2.5% (w/v) copolymer had an excellent syringeability. Insulin was released up to 80% over a period of 20 days. Insulin kept its initial folding after formulating and releasing from SMGel. A supramolecular hydrogel based on complexation of triblock PCL-PEG-PCL copolymer with γ-cyclodextrin is a suitable system for providing sustained release of therapeutic proteins, with desirable flow behaviour.Key words: insulin, PCL-PEG-PCL, supramolecular hydrogel, triblock copolymer, γ-CD     

New amphiphilic poly(2-ethyl-2-oxazoline)/ poly(L-lactide) triblock copolymers

A new series of cationic, thermo-sensitive, and biodegradable poly(L-lactide)-poly(2-ethyl-2-oxazoline)-poly(L-lactide) (PLLA-PEOz-PLLA) triblock copolymers were synthesized by ring-opening polymerization. With increasing molecular weight and crystallinity of hydrophobic PLLA blocks, the critical micellization concentrations (CMC) occurred at lower concentration. The PLLA-PEOz-PLLA aqueous solution was transparent at room temperature. Heating the solution resulted in precipitations, which were caused by the combination of dehydration of water around PEOz and the aggregations of PLLA segments. Acid/base titration profiles indicated that PLLA-PEOz-PLLA were protonated at neutral and acidic conditions. Considerable buffering capacity was found over the entire pH range. The specific PLLA-PEOz-PLLA triblock copolymers with thermal- and pH-sensitive properties can be tailored by varying the compositions and can be applied as controlled release carries for biomedical applications.     

Biodegradable and pH-sensitive hydrogels for cell encapsulation and controlled drug release

Hydrogels with pH-sensitive poly(acrylic acid) (PAAc) chains and biodegradable acryloyl-poly(-caprolactone)-2-hydroxylethyl methacrylate (AC-PCL-HEMA) chains were designed and synthesized. The morphology of hydrogel was observed by scanning electron microscopy. The degradation of the hydrogel in the presence of Pseudomonas lipase was studied. The in vitro release of bovine serum albumin from the hydrogel was investigated. Cytotoxicity study shows that the AC-PCL-HEMA/AAc copolymer exhibits good biocompatibility. Cell adhesion and migration into the hydrogel networks were evaluated by using different cell lines. The hydrogel with a lower cross-linking density and a larger pore size exhibited a better performance for cells migration.     

Self-assembled micelles of biodegradable triblock copolymers based on poly(ethyl ethylene phosphate) and poly(-caprolactone) as drug carriers

A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL block lengths were synthesized and characterized. These triblock copolymers formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution. The micelle morphology was spherical, determined by transmission electron microscopy. It was found that the size and critical micelle concentration values of the micelles depended on both hydrophobic PCL block length and PEEP hydrophilic block length. The in vitro degradation characteristics of the triblock copolymers were investigated in micellar form, showing that these copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas lipase and phosphodiesterase I. These triblock copolymers were used for paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX was successfully loaded into the micelles, and the in vitro release profile was found to be correlative to the polymer composition. These biodegradable triblock copolymer micelles are potential as novel carriers for hydrophobic drug delivery.     

Synthesis and characterization of RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) triblock copolymer

Advances in tissue engineering require biofunctional scaffolds that can provide not only physical support for cells but also chemical and biological cues needed in forming functional tissues. To achieve this goal, a novel RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) (PEG-PLA-PGL/RGD) was synthesized in four steps (1) to prepare diblock copolymer PEG-PLA-OH and to convert its -OH end group into -NH(2) (to obtain PEG-PLA-NH(2)), (2) to prepare triblock copolymer PEG-PLA-PBGL by ring-opening polymerization of NCA (N-carboxyanhydride) derived from benzyl glutamate with diblock copolymer PEG-PLA-NH(2) as macroinitiator, (3) to remove the protective benzyl groups by catalytic hydrogenation of PEG-PLA-PBGL to obtain PEG-PLA-PGL, and (4) to react RGD (arginine-glycine-(aspartic amide)) with the carboxyl groups of the PEG-PLA-PGL. The structures of PEG-PLA-PGL/RGD and its precursors were confirmed by (1)H NMR, FT-IR, amino acid analysis, and XPS analysis. Addition of 5 wt % PEG-PLA-PGL/RGD into a PLGA matrix significantly improved the surface wettability of the blend films and the adhesion and proliferation behavior of human chondrocytes and 3T3 cells on the blend films. Therefore, the novel RGD-grafted triblock copolymer is expected to find application in cell or tissue engineering.     

Fine tuning micellar core-forming block of poly(ethylene glycol)-block-poly(ε-caprolactone) amphiphilic copolymers based on chemical modification for the solubilization and delivery of doxorubicin

This study aimed to optimize poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL)-based amphiphilic block copolymers for achieving a better micellar drug delivery system (DDS) with improved solubilization and delivery of doxorubicin (DOX). First, the Flory-Huggins interaction parameters between DOX and the core-forming segments [i.e., poly(ε-caprolactone) (PCL) and poly[(ε-caprolactone-co-γ-(carbamic acid benzyl ester)-ε-caprolactone] (P(CL-co-CABCL))] was calculated to assess the drug-polymer compatibility. The results indicated a better compatibility between DOX and P(CL-co-CABCL) than that between DOX and PCL, motivating the synthesis of monomethoxy-poly(ethylene glycol)-b-poly[(ε-caprolactone-co-γ-(carbamic acid benzyl ester)-ε-caprolactone] (mPEG-b-P(CL-co-CABCL)) block copolymer. Second, two novel block copolymers of mPEG-b-P(CL-co-CABCL) with different compositions were prepared via ring-opening polymerization of CL and CABCL using mPEG as a macroinitiator and characterized by (1)H NMR, FT-IR, GPC, WAXD, and DSC techniques. It was found that the introduction of CABCL decreased the crystallinity of mPEG-b-PCL copolymer. Micellar formation of the copolymers in aqueous solution was investigated with fluorescence spectroscopy, DLS and TEM. mPEG-b-P(CL-co-CABCL) copolymers had a lower critical micelle concentration (CMC) than mPEG-b-PCL and subsequently led to an improved stability of prepared micelles. Furthermore, both higher loading capacity and slower in vitro release of DOX were observed for micelles of copolymers with increased content of CABCL, attributed to both improved drug-core compatibility and favorable amorphous core structure. Meanwhile, DOX-loaded micelles facilitated better uptake of DOX by HepG2 cells and were mainly retained in the cytosol, whereas free DOX accumulated more in the nuclei. However, possibly because of the slower intracellular release of DOX, DOX-loaded micelles were less potent in inhibiting cell proliferation than free DOX in vitro. Taken together, the introduction of CABCL in the core-forming block of mPEG-b-PCL resulted in micelles with superior properties, which hold great promise for drug delivery applications.     

Injectable and sustained delivery of human growth hormone using chemically modified Pluronic copolymer hydrogels

A new injectable biodegradable hydrogel system with thermosensitive sol-gel transition behavior was developed. A series of A-B-A triblock copolymers consisting of Pluronic copolymer end-capped with D- or L-lactic acid oligomers (PL-LA(n)) with various chain lengths (n = 5,12) was synthesized. It was assumed that a pair of two triblock copolymers with enantiomeric oligolactide chains, when blended in an equimolar mixture, would form more stable, self-assembled, and stereocomplexed (ST) hydrogels. A series of blend hydrogels encapsulating human growth hormone (hGH) was prepared by varying blend ratios between PL and stereocomplexed PL copolymers. They showed sustained release of hGH via an erosion-dependent mechanism. The hydrogel with a 5% blending ratio exhibited the most delayed mass erosion as well as sustained protein release patterns in vitro possibly due to the formation of a fish-net like 3-D mesh structure. The effect of incubation condition on hGH release and degradation behaviors was also assessed.     

Responsive glyco-poly(2-oxazoline)s: synthesis, cloud point tuning, and lectin binding

A new sugar-substituted 2-oxazoline monomer was prepared using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Its copolymerization with 2-ethyl-2-oxazoline as well as 2-(dec-9-enyl)-2-oxazoline, yielding well-defined copolymers with the possibility to tune the properties by thiol-ene "click" reactions, is described. Extensive solubility studies on the corresponding glycocopolymers demonstrated that the lower critical solution temperature behavior and pH-responsiveness of these copolymers can be adjusted in water and phosphate-buffered saline (PBS) depending on the choice of the thiol. By conjugation of 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranose and subsequent deprotection of the sugar moieties, the hydrophilicity of the copolymer could be increased significantly, allowing a cloud-point tuning in the physiological range. Furthermore, the binding capability of the glycosylated copoly(2-oxazoline) to concanavalin A was investigated.     

Evaluation of Poly(2-Ethyl-2-Oxazoline) Containing Copolymer Networks of Varied Composition as Sustained Metoprolol Tartrate Delivery Systems

Segmented copolymer networks (SCN) based on poly(2-ethyl-2-oxazoline) and containing 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, and/or methyl methacrylate segments have been evaluated as potential sustained release systems of the water soluble cardioselective β-blocker metoprolol tartrate. The structure and properties of the drug carriers were investigated by differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. Swelling kinetics of SCNs in various media was followed, and the conditions for effective MT loading were specified. MT-loaded SCNs with drug content up to 80 wt.% were produced. The release kinetics of metoprolol tartrate from the systems was studied and it was shown that the conetworks of different structure and composition are able to sustain the metoprolol tartrate release without additional excipients.     

Intracameral bevacizumab and mitomycin C Trabeculectomy for eyes with neovascular glaucoma: a case series

The purpose of this study was to describe the surgical outcomes and safety of intracameral bevacizumab during trabeculectomy in eyes with neovascular glaucoma. Pilot study included four eyes (four patients) with refractory neovascular glaucoma submitted to fornix-based trabeculectomy with adjunctive use of bevacizumab in the anterior chamber during the procedure. Patients were previously treated with panretinal photocoagulation as standard therapy. Variables evaluated were intraocular pressure, bleb appearance, iris neovascularization, intraoperative/postoperative complications, and visual outcomes. No intraoperative complication was observed. The mean follow-up period was 12.75 (range, 12–15 months). All eyes showed significant intraocular pressure control postoperatively. Iris neovascularization reduced significantly within 1 month after surgery. Mild anterior chamber inflammation was observed during follow-up in all eyes. No significant postoperative complication was observed, and no patient presented visual acuity deterioration. Intracameral bevacizumab may be used as an adjunctive therapy during trabeculectomy in eyes with neovascular glaucoma.     

Thermodynamic confinement and alpha-helix persistence length in poly(gamma-benzyl-L-glutamate)-b-poly(dimethyl siloxane)-b-poly(gamma-benzyl-L-glutamate) triblock copolymers

The structure and the associated dynamics of a series of poly(gamma-benzyl-L-glutamate)-b-poly(dimethyl siloxane)-b-poly(gamma-benzyl-L-glutamate) (PBLG-b-PDMS-b-PBLG) triblock copolymers were investigated using small- and wide-angle X-ray scattering, NMR, transmission electron microscopy, and dielectric spectroscopy, respectively. The structural analysis revealed phase separation in the case of the longer blocks with defected alpha-helical segments embedded within the block copolymer nanodomains. The alpha-helical persistence length was found to depend on the degree of segregation; thermodynamic confinement and chain stretching results in the partial annihilation of helical defects.     

Destruction of Pseudomonas aeruginosa pre-formed biofilms by cationic polymer micelles bearing silver nanoparticles

Abstract

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen often associated with biofilm infections. This study evaluated the capacity for biofilm destruction of a novel combination of cationic polymer micelles formed from poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA-PCL-PDMAEMA) triblock copolymer either alone, or loaded with silver nanoparticles (M_AgNPs). Pre-formed P. aeruginosa biofilms were incubated with either blank micelles, AgNO₃, or M_AgNPs. Biofilm biomass (crystal violet assay), metabolic activity (Alamar blue reduction), structure (SEM) and viability (CLSM after Live/Dead staining, or plating for CFU) were checked. The results showed that the micelles alone loosened the biofilm matrix, and caused some alterations in the bacterial surface. AgNO₃ killed the bacteria in situ leaving dead biofilm bacteria on the surface. M_AgNPs combined the two types of activities causing significant biofilm reduction, and alteration and death of biofilm bacteria. Therefore, the applied PDMAEMA-based micelles appear to be a successful candidate for the treatment of P. aeruginosa biofilm infections.     

Thermally controlled release of anticancer drug from self-assembled γ-substituted amphiphilic poly(ε-caprolactone) micellar nanoparticles

A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL-b-POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)(2)) catalyst and a fluorescent dansyl initiator. The PMEEECL-b-POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.     

Synthesis and characterization of glycopolymer-polypeptide triblock copolymers

Glycopolymer-polypeptide triblock copolymers of the structure, poly(l-alanine)-b-poly(2-acryloyloxyethyl-lactoside)-b-poly(l-alanine) (AGA), have been synthesized by sequential atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP). Controlled free radical polymerization of 2-O-acryloyl-oxyethoxyl-(2,3,4,6-tetra-O-acetyl-beta-d-galactopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-beta-d-glucopyranoside (AEL) by ATRP with a dibromoxylene (DBX)/CuBr/bipy complex system was used to generate a central glycopolymer block. Telechelic glycopolymers with diamino end groups were obtained by end group transformation and subsequently used as macroinitiators for ROP of l-alanine N-carboxyanhydride monomers (Ala-NCA). Gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy analysis demonstrated that copolymer molecular weight and composition were controlled by both the molar ratios of the Ala-NCA monomer to macroinitiator and monomer conversion and exhibited a narrow distribution (Mw/Mn = 1.06-1.26). FT-IR spectroscopy of triblock copolymers revealed that the ratio of alpha-helix/beta-sheet increased with poly(l-alanine) block length. Of note, transmission electron microscopy (TEM) demonstrated that selected amphiphilic glycopolymer-polypeptide triblock copolymers self-assemble in aqueous solution to form nearly spherical aggregates of several hundreds nanometer in diameter. Significantly, the sequential application of ATRP and ROP techniques provides an effective method for producing triblock copolymers with a central glycopolymer block and flanking polypeptide blocks of defined architecture, controlled molecular weight, and low polydispersity.     

Macromolecular design of aliphatic polyesters with maintained mechanical properties and a rapid, customized degradation profile

An innovative type of triblock copolymer that maintains and even increases the mechanical properties of poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL) with a controlled, predictable, and rapid degradation profile has been synthesized. Elastic triblock copolymers were formed from the hydrophobic and crystalline PLLA and PCL with an amorphous and hydrophilic middle block of poly(but-2-ene-1,4-diyl malonate) (PBM). The polymers were subjected to degradation in PBS at 37 °C for up to 91 days. Prior to degradation, ductility of the PLLA-PBM-PLLA was approximately 4 times greater than that of the homopolymer of PLLA, whereas the modulus and tensile stress at break were unchanged. A rapid initial hydrolysis in the amorphous PBM middle block changed the microstructure from triblock to diblock with a significant reduction in ductility and molecular weight. The macromolecular structure of the triblock copolymer of PLLA and PBM generates a more flexible and easier material to handle during implant, with the advantage of a customized degradation profile, demonstrating its potential use in future biomedical applications.     

MPEG-PCL Copolymeric Micelles for Encapsulation of Azithromycin

Macrolide antibiotics are lipophilic drugs with some limitations including low solubility, limited cellular permeation, patients discomfort, etc. With amphiphilic methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL) copolymer and azithromycin (AZT) as drug carrier and model drug, AZT-loaded micelles were prepared via thin-membrane hydration method in order to overcome these limitations. Encapsulation efficiency of AZT-loaded micelles was 94.40% with good storage stability for 28 days, and AZT’s water solubility was enhanced to 944 μg/mL. Fourier transform infrared spectrum and x-ray diffraction analysis indicated that AZT was enveloped into the micelles in amorphous form due to its interaction with the copolymer. AZT’s in vitro release from the AZT-loaded micelles demonstrated a slow and continuous behavior when compared with raw AZT. The release dynamics was accorded with Weibull equation, meaning that release amount of AZT lowered with time and was proportional to remaining amount of drug in the AZT-loaded micelles. Korsmeyer-Peppas fitting result suggested that drug release process was a classical Fickian diffusion-controlled manner. With Staphylococcus aureus as bacterial strain, antibacterial activity of the AZT-loaded micelles displayed was comparable with raw AZT. In conclusion, MPEG-PCL should be a promising carrier for macrolide antibiotic delivery in treatment of bacterial infections.     

Long-Term Outcomes and Prognostic Factors of Trabeculectomy following Intraocular Bevacizumab Injection for Neovascular Glaucoma

Purpose

To evaluate long-term outcomes and identify prognostic factors of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma.

Methods

Sixty-one eyes of 54 patients with neovascular glaucoma treated by trabeculectomy following intraocular bevacizumab injection were consecutively enrolled. Surgical success criteria were sufficient intraocular pressure (IOP) reduction (IOP ≤21 mmHg, ≥20% IOP reduction, no additional medications or glaucoma surgeries) without devastating complications (loss of light perception, phthisis bulbi, and endophthalmitis) or significant hypotony (IOP ≤5 mmHg continued ≥6 months and until the last follow-up visit or hypotony requiring intervention). Kaplan-Meier survival curves and Cox regression analysis were used to examine success rates and risk factors for surgical outcomes.

Results

The follow-up period after trabeculectomy was 45.0 ± 22.2 months (mean ± standard deviation). Surgical success rate was 86.9 ± 4.3% (± standard error), 74.0 ± 6.1%, and 51.3 ± 8.6% at 1, 3, and 5 years. Multivariate Cox regression analysis identified two risk factors; lower preoperative IOP (≤30 mmHg) for surgical failure and hypotony [hazard ratio (HR), 2.92, 6.64; 95% confidence interval (CI), 1.22 to 7.03, 1.47 to 30.0; P = 0.018, 0.014, respectively], and vitrectomy after trabeculectomy for surgical failure with or without hypotony criteria (HR, 2.32, 4.06; 95% CI, 1.02 to 5.28, 1.30 to 12.7; P = 0.045, 0.016, respectively).

Conclusions

The long-term outcomes of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma were favorable. Lower baseline IOP was associated with development of significant hypotony, while additional vitrectomy was related to insufficient IOP reduction.     

Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation.