Wound healing properties of triple cross-linked poly (vinyl alcohol)/methacrylate kappa-carrageenan/chitooligosaccharide hydrogel.

To develop an effective and mechanically robust wound dressing, a poly (vinyl alcohol) (PVA)/methacrylate kappa-carrageenan (κ-CaMA) composite hydrogel encapsulated with a chitooligosaccharide (COS) was prepared in a cassette via repeated freeze/thaw cycles, photo-crosslinking, and chemical cross-linking. The chemical, physical, mechanical, in vitro biocompatibility, in vivo wound-healing properties, and antibacterial activity of triple-crosslinked hydrogel were subsequently characterized. The results showed that the PVA/κ-CaMA/COS (Pκ-CaC) hydrogel had a uniformly thick, highly porous three-dimensional architecture with uniformly distributed pores, a high fluid absorption, and retention capacity without disturbing its mechanical stability, and good in vitro biocompatibility. Macroscopic images from the full-thickness skin wound model revealed that the wounds dressed with the proposed Pκ-CaC hydrogel were completely healed by day 14, while the histomorphological results confirmed full re-epithelization and rapid skin-tissue remodeling. This study thus indicates that the composite Pκ-CaC hydrogel has significant potential for use as a wound dressing.

Enhanced skin adhesive property of α-cyclodextrin/nonanyl group-modified poly(vinyl alcohol) inclusion complex film.

For skin contact medical devices, realizing a strong contact with skin is essential to precisely detect human biological information and enable human-machine interaction. In this study, we aimed to fabricate and characterize an inclusion complex film (ICF) for skin adhesion using α-cyclodextrin (α-CD) and nonanyl group-modified PVA (C9-PVA) under wet conditions. Based on the water insolubility of C9-PVA and the inclusion ability of α-CD for alkyl groups, α-CD/C9-PVA ICF was prepared. Among the prepared ICFs, α-CD/2.5C9-PVA (w/w = 0.5) ICF showed the highest bonding strength and T-peeling strength to porcine skin. Furthermore, α-CD/2.5C9-PVA (w/w = 0.5) ICF had better water vapor transmission rate than that of commercial tapes. In addition, the ion permeability test revealed that α-CD/2.5C9-PVA (w/w = 0.5) ICF exhibited excellent Na and Cl ion permeability. These results demonstrated that the multi-functional α-CD/2.5C9-PVA (w/w = 0.5) ICF can be a promising adhesive for skin contact medical devices.

Preparation and Characterization of Poly(ethylene-co-vinyl alcohol)/poly(ε-caprolactone) Blend for Bioscaffolding Applications.

In order to improve the cell adhesion on poly(ε-caprolactone) (PCL) scaffolds, poly(ethylene-co-vinyl alcohol) (E-VAL) which has hydroxyl groups capable of developing hydrogen bonds with celling was blended with this polymer. To reach this goal, a series of E-VAL/PCL blends with different compositions were prepared by the solvent casting method. The miscibility of the polymer blend was proved by differential scanning calorimetry and Fourier-transform infrared spectroscopy spectrometry. Furthermore, the mechanical properties of the polymer blends were assessed in their wet state by dynamic mechanical analysis. The surfaces wettability of blends and their components were examined through static contact angle measurements. The pore interconnections in the resulted scaffolds were achieved by the incorporation of naphthalene microparticles which were used as porogen and then removed in its gas state by sublimation under reduced pressure. The presence of pores interconnected inside the polymeric materials and their surface morphologies was examined by scanning electron microscopy. The in-vitro cytotoxicity and cell adhesion on the prepared materials were examined by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.

Bronchoscopic interventions for severe emphysema: Where are we now?

Patients with severe emphysema have limited treatment options and only derive a small benefit from optimal medical treatment. The only other therapy to have significant clinical beneficial effect in emphysema is LVRS but the perceived risk and invasiveness of surgery has fuelled bronchoscopic approaches to induce lung volume reduction. There are multiple bronchoscopic methods for achieving volume reduction in severe emphysema: EBV, airway bypass procedure, endobronchial coils, thermal (vapour) sclerosis and chemical sclerosis (sealants). Optimal patient selection is key to successful patient outcomes. This review discusses bronchoscopic approaches for emphysema treatment which has progressed through clinical trials to clinical practice.

SiO2-PVA-Fe(acac)3 Hybrid Based Superparamagnetic Nanocomposites for Nanomedicine: Morpho-textural Evaluation and In Vitro Cytotoxicity Assay.

A facile sol-gel route has been applied to synthesize hybrid silica-PVA-iron oxide nanocomposite materials. A step-by-step calcination (processing temperatures up to 400 °C) was applied in order to oxidize the organics together with the iron precursor. Transmission electron microscopy, X-ray diffraction, small angle neutron scattering, and nitrogen porosimetry were used to determine the temperature-induced morpho-textural modifications. In vitro cytotoxicity assay was conducted by monitoring the cell viability by the means of MTT assay to qualify the materials as MRI contrast agents or as drug carriers. Two cell lines were considered: the HaCaT (human keratinocyte cell line) and the A375 tumour cell line of human melanoma. Five concentrations of 10 µg/mL, 30 µg/mL, 50 µg/mL, 100 µg/mL, and 200 µg/mL were tested, while using DMSO (dimethylsulfoxid) and PBS (phosphate saline buffer) as solvents. The HaCaT and A375 cell lines were exposed to the prepared agent suspensions for 24 h. In the case of DMSO (dimethyl sulfoxide) suspensions, the effect on human keratinocytes migration and proliferation were also evaluated. The results indicate that only the concentrations of 100 µg/mL and 200 µg/mL of the nanocomposite in DMSO induced a slight decrease in the HaCaT cell viability. The PBS based in vitro assay showed that the nanocomposite did not present toxicity on the HaCaT cells, even at high doses (200 µg/mL agent).

Electrospun Microbial-Encapsulated Composite-Based Plasticized Seed Coat for Rhizosphere Stabilization and Sustainable Production of Canola ( Brassica napus L.).

Plant-growth-promoting bacteria show promises in crop production; nevertheless, innovation in their stable delivery is required for practical use by farmers. Herein, the composite of poly(vinyl alcohol)/poly(vinylpyrrolidone) plasticized with glycerol and loaded with the microbial consortium ( Bacillus subtilis plus Seratia marcescens) was fabricated and engineered onto canola ( Brassica napus L.) seed via electrospinning. Scanning electron microscopy showed that the biocomposite is a one-dimensional membrane, which encapsulated microbes in a multilayered nanostructure, and their interfacial behavior between microorganism and seed is beneficial for safer farming. A universal testing machine and thermogravimetric analysis demonstrated that the biocomposite holds sufficient thermomechanical properties for stable handling and practical management. A spectroscopic study resolved the living hybrid-polymer structure of the biocomposite and proved the plasticizing role of glycerol. A swelling study supports the degradation of the biocomposite in the hydrophilic environment as a result of the leaching of the plasticizer, which is important for the sustained release of microbial cells. A shelf life study supported that the biocomposite seed coat placed a threshold level of microbes [5.675 ± 0.48 log10 colony forming units (CFU)/seed] and maintained their satisfactory viability for 15 days at room temperature. An antifungal and nutrient-solubilizing study supported that the biocomposite seed coat could provide opportunities to biocontrol diseases and improve nutrient acquisition by the plant. A pot study documents the better performance of the biocomposite seed coat on seed germination, seedling growth, leaf area, plant dry biomass, and root system. A chemical and microbial study demonstrated that the biocomposite seed coat improved the effectiveness of the bioinoculant in the root-soil interface, where they survive, flourish, and increase the nutrient pool status. In particular, this study presents advances in the fabrication of the biocomposite for encapsulation, preservation, sustained release, and efficacious use of microorganisms onto seeds for precision farming.

Long-term Imaging of the Lungs After Sealant Bronchoscopic Lung Volume Reduction.

PURPOSE: The aim of the study was to assess the pulmonary temporal changes after bronchoscopic lung volume reduction (BLVR) using sealants for treatment of emphysema. MATERIALS AND METHODS: We retrospectively assessed all chest computerized tomography (CT) and F-18 fluorodeoxyglucose (FDG) positron emission tomography CT scans of patients treated at our institution with BLVR. RESULTS: Eleven patients were treated with sealants: 4 with biological sealants and 7 with synthetic sealants. The first CT scan after biological sealant treatment showed no abnormalities in 8 lobes and 5 nodules, and 3 consolidations in 7 lobes. All findings resolved within 3 months, except for a nodule that decreased after 2 months and remained stable for 9 years. The first CT scan after utilizing the synthetic sealant showed abnormalities in each treated lobe: 19 nodules/masses (16 cavitary, 3 solid) and 3 consolidations. Follow-up CT scans were available for 16 nodules/masses: 1 resolved, 12 slowly decreased in size, 1 remained unchanged, and 2 grew. Of 3 consolidations 1 resolved and 2 decreased in size. FDG positron emission tomography CT scans performed in 2 patients showed FDG uptake higher than mediastinal background activity in 2 nodules in the same patient. CONCLUSIONS: Pulmonary changes after BLVR are variable. After treatment with biological sealants, most findings resolve within 3 months. In contrast, after synthetic sealants, although the majority regress over time, some show waxing and waning in growth that can mimic malignancy. FDG uptake in some of these lesions is suggestive of chronic inflammation. Radiologists should be aware of the spectrum of these pulmonary changes to avoid misdiagnosis of lung cancer.

Mechanoresponsiveness of human umbilical cord mesenchymal stem cells in in vitro chondrogenesis-A comparative study with growth factor induction.

Fetal-derived mesenchymal stem cells especially human umbilical cord matrix mesenchymal stem cells (hUCMSCs), with their ease of availability, pluripotency, and high expansion potential have emerged as an alternative solution for stem cell based cartilage therapies. An attempt to elucidate the effect of dynamic mechanical compression in modulating the chondrogenic differentiation of hUCMSCs is done in this study to add on to the knowledge of optimizing chondrogenic signals necessary for the effective differentiation of these stem cells and subsequent integration to the surrounding tissues. hUCMSCs were seeded in porous poly (vinyl alcohol)-poly (caprolactone) (PVA-PCL) scaffolds and cultured in chondrogenic medium with/without TGF-ß3 and were subjected to a dynamic compression of 10% strain, 1 Hz for 1/4 h for 7 days. The results on various analysis shows that the extent of dynamic compression is an important factor affecting cell viability. Mechanical stimulation in the form of dynamic compression stimulates expression of chondrogenic genes even in the absence of chondrogenic growth factors and also augments growth factor induced chondrogenic potential of hUCMSC. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2554-2566, 2016.

Immobilization of Lipid Substrates: Application on Phospholipase A2 Determination.

The purpose of the study was to assess a fluorimetric assay for the determination of total phospholipase A(2) (PLA(2)) activity in biological samples introducing the innovation of immobilized substrates on crosslinked polymeric membranes. The immobilized C(12)-NBD-PtdCho, a fluorescent analogue of phosphatidylcholine, exhibited excellent stability for 3 months at 4 °C and was not desorbed in the aqueous reaction mixture during analysis. The limit of detection was 0.5 pmol FA (0.2 pg) and the linear part of the response curve extended from 1 up to 190 nmol FA/h/mL sample. The intra- and inter-day relative standard deviations (%RSD), were ≤6 and ≤9 %, respectively. Statistical comparison with other fluorescent methods showed excellent correlation and agreement. Semiempirical calculations showed a fair amount of electrostatic interaction between the NBD-labeled substrate and the crosslinked polyvinyl alcohol with the styryl pyridinium residues (PVA-SbQ) material, from the plane of which, the sn-2 acyl chain of the phospholipid stands out and is accessible by PLA(2). Atomic Force Microscopy revealed morphological alterations of the immobilized substrate after the reaction with PLA(2). Mass spectrometry showed that only C(12)-NBD-FA, the PLA(2 )hydrolysis product, was detected in the reaction mixture, indicating that PLA(2) recognizes PVA-SbQ/C(12)-NBD-PtdCho as a surface to perform catalysis.

Charge-conversional and reduction-sensitive poly(vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin release.

Charge-conversional and reduction-sensitive polyvinyl alcohol (PVA) nanogels were developed for efficient cancer treatment by enhanced cell uptake and intracellular triggered doxorubicin (DOX) release. These PVA nanogels were prepared in a straightforward manner by inverse nanoprecipitation via "click" reaction with an average diameter of 118nm. The introduction of COOH into the PVA nanogels efficiently improved the DOX encapsulation due to the electrostatic interaction. The in vitro release result showed that the decrease of electrostatic interaction between COOH and DOX under a mimicking endosomal pH, in combination with the cleavage of the intervening disulfide bonds in response to a high glutathione (GSH) concentration led to a fast and complete release of DOX. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the ultra pH-sensitive terminal groups allowed nanogels to reverse their surface charge from negative to positive under a tumor extracellular pH (6.5-6.8) which facilitated cell internalization. MTT assays and real time cell analysis (RTCA) showed that these DOX-loaded charge-conversional and reducible PVA nanogels had much better cell toxicity than DOX-loaded non-charge-conversional or reduction-insensitive PVA nanogels following 48h of incubation. These novel charge-conversional and stimuli-responsive PVA nanogels are highly promising for targeted intracellular anticancer drug release.

Preparation and evaluation of high dispersion stable nanocrystal formulation of poorly water-soluble compounds by using povacoat.

In this study, we reported the application of Povacoat®, a hydrophilic polyvinylalcohol copolymer, as a dispersion stabilizer of nanoparticles of poorly water-soluble compounds. In addition, the influence of aggregation of the nanoparticles on their solubility and oral absorption was studied. Griseofulvin (GF) was used as a model compound with poor water solubility and was milled to nanoparticles by wet bead milling. The dispersion stability of GF milled with Povacoat® or the generally used polymers (polyvinylalcohol, hydroxypropylcellulose SSL, and polyvinylpyrrolidone K30) was compared. Milled GF suspended in Povacoat® aqueous solution with D-mannitol, added to improve the disintegration rate of freeze-dried GF, exhibited high dispersion stability without aggregation (D90 = ca. 0.220 µm), whereas milled GF suspended in aqueous solutions of the other polymers aggregated (D90 > 5 µm). Milled GF with Povacoat® showed improved aqueous solubility and bioavailability compared with the other polymers. The aggregation of nanoparticles had significant impact on the solubility and bioavailability of GF. Povacoat® also prevented the aggregation of the various milled poorly water-soluble compounds (hydrochlorothiazide and tolbutamide, etc.) more effectively than the other polymers. These results showed that Povacoat® could have wide applicability to the development of nanoformulations of poorly water-soluble compounds.

Horseradish peroxidase-catalyzed formation of hydrogels from chitosan and poly(vinyl alcohol) derivatives both possessing phenolic hydroxyl groups.

Horseradish peroxidase-catalyzed cross-linking was applied to prepare hydrogels from aqueous solutions containing chitosan and poly(vinyl alcohol) derivatives both possessing phenolic hydroxyl groups (denoted as Ph-chitosan and Ph-PVA, respectively). Comparing the hydrogels prepared from the solution of 1.0% (w/v) Ph-chitosan and 3.0% (w/v) Ph-PVA and that of 3.0% (w/v) Ph-chitosan and 1.0% (w/v) Ph-PVA, the gelation time of the former hydrogel was 47 s, while was 10s longer than that of the latter one. The breaking point for the former hydrogel under stretching (114% strain) was approximately twice larger than that for the latter one. The swelling ratio of the former hydrogel in saline was about half of the latter one. Fibroblastic cells did not adhere on the former hydrogel but adhered and spread on the latter one. The growth of Escherichia coli cells was fully suppressed on the latter hydrogel during 48 h cultivation.

Conducting hydrogels of tetraaniline-g-poly(vinyl alcohol) in situ reinforced by supramolecular nanofibers.

Novel conducting hydrogels (PVA-TA) with dual network structures were synthesized by the grafting reaction of tetraaniline (TA) into the main chains of poly(vinyl alcohol) and in situ reinforced by self-assembly of a sorbitol derivative as the gelator. The chemical structure of the PVA-TA hydrogels was characterized by using FT-IR and NMR. The mechanical strength of the PVA-TA hydrogels was strongly improved due to the presence of supramolecular nanofibers. For instance, the compressive and tensile strengths of supramolecular nanofiber-reinforced hydrogels were, respectively, 10 times and 5 times higher than those of PVA-TA hydrogels. Their storage modulus (G') and loss modulus (G″) were 5 times and 21 times higher than those of PVA-TA hydrogels, respectively. Cyclic voltammetry and conductivity measurements indicated that the electroactivity of reinforced hydrogels is not influenced by the presence of supramolecular nanofibers.

Poly(N-vinyl-2-pyrrolidone-co-vinyl alcohol), a versatile amphiphilic polymeric scaffold for multivalent probes.

A convenient scaffold based on poly(N-vinyl-2-pyrrolidone-co-vinyl alcohol) is proposed for presenting ligands in multivalent format. This amphiphilic polymer supports synthesis of conjugates in both organic and aqueous media, permits enzymatic processing of the ligand precursor, and, finally, offers a choice of formats for evaluation of biological activity either as a soluble inhibitor or as a capture reagent after deposition on a hydrophobic surface or standard microtiter plates.

Treatment of severe advanced emphysema with volume reduction using lung sealant: a case report of 2 patients.

BACKGROUND: Emphysema is a progressive and irreversible disease for which there is no cure to date. The patients experience debilitating shortness of breath with repetitive exacerbations and poor quality of daily life. At present, patients with severe emphysema have limited treatment options. Endoscopic lung-volume reduction with valve implantation or using lung sealant is a treatment option for patients with severe emphysema. By our patients, we detected collateral channels, which allow airflow into the target lobe and prevent atelectasis and significant lung-volume reduction. Thus, we decided to treat the advanced emphysema of our patients with endoscopic volume reduction using lung sealant (AeriSeal). Lung-volume reduction surgery reduces hyperinflation and improves lung function by removal of emphysematous lung tissue. However, lung-volume reduction surgery is also associated with significant short-term morbidity and mortality. Results from recently published Endobronchial Valve for Emphysema Palliation Trail (VENT) and Exhale Airway Stents for Emphysema (EASE) trial showed that treatment was substantially less effective and did not consistently reduce hyperinflation or improve lung function mostly likely due to collateral ventilation present in majority of patients. There is a volume reduction therapy in case of detection of collateral flow; use of a lung sealant is a possible alternative. METHODS: A novel endoscopic tissue sealant (AeriSeal; Aeris Therapeutics, Woburn, MA) is a liquid foam sealant that collapses hyperinflated lung areas destroyed by emphysema. The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue, forming a film of material on the lung surface that seals the target region to cause durable absorption atelectasis. RESULTS: Two patients with advanced emphysema and hyperinflation underwent endoscopic volume reduction with endoscopic tissue sealant (AeriSeal); collateral flow was confirmed by using the Chartis System. Both patients experienced transient fever, malaise, chest discomfort, and shortness of breath for about 3 days after the procedure. Over a period of 8 and 12 weeks, the air within the sealed region was absorbed and the treated area showed atelectasis on computed tomography scan. The follow-up evaluations of those 2 patients showed improved lung function (increased FEV1, and a reduction of TLC and RV) with improved quality of life of both patients. CONCLUSIONS: Correlation and comparisons between changes in primary and secondary outcome measures in the lung function parameters and 6-minute walking test before and after the application of AeriSealant revealed significant reduction of hyperinflation and improvement both in the flow rates and physical capacity of our patients.

Effect of fissure integrity on lung volume reduction using a polymer sealant in advanced emphysema.

RATIONALE: Interlobar fissure integrity has previously correlated with responsiveness to endobronchial lung volume reduction therapy in patients with advanced emphysema. OBJECTIVE: This report summarises the effect of interlobar fissure integrity on responses to treatment with a novel endoscopic tissue sealant (AeriSeal emphysematous lung sealant (ELS)) that collapses hyperinflated lung. METHODS: Fissure status, lung volumes, tissue density and disease heterogeneity were assessed radiographically in 28 patients (age 63.4±6.1 years, 20 men) with advanced upper lobe predominant emphysema (density=888.0±18.2 HU; upper lobe tissue density < -950 = 2.62±1.74). Post-treatment changes in lobar volume, pulmonary function, exercise capacity, symptoms and quality of life were compared in patients with complete fissures (CFs) and incomplete fissures (ICFs). RESULTS: ELS therapy reduced lung volumes independent of interlobar fissure integrity. In patients with upper lobe emphysema and CFs, lobar volume reduction was 214±127 ml/treatment compared with 256±175 ml/treatment in those with ICFs (p=0.453). Reductions in gas trapping and improvements in spirometry, functional capacity and quality of life were similar in patients with CFs and ICFs. Stepwise multiple regression modelling confirmed that fissure integrity did not contribute to post-treatment changes in forced expiratory volume in 1 s, residual volume/total lung capacity ratio or lobar volume measured by CT analysis. CONCLUSIONS: Interlobar fissure integrity, an important determinant of responsiveness to endobronchial lung volume reduction therapy in prior studies, had minimal impact on physiological and functional responses to ELS therapy in patients with severe upper lobe predominant emphysema. CLINICAL TRIAL REGISTRATION NUMBER: Registration numbers for trials contributing to datasets in this report: NCT00884962, NCT01051258 and NCT01181466.

Enhanced cellular delivery of idarubicin by surface modification of propyl starch nanoparticles employing pteroic acid conjugated polyvinyl alcohol.

Enhanced intracellular internalization of the anti-cancer active idarubicin (IDA) was achieved through appropriate surface modification of IDA loaded propyl starch nanoparticles. This was conducted by synthesizing pteroic acid modified polyvinyl alcohol (ptPVA) and employing this stabilizer for formulating the said nanoparticles. Pteroic acid attached at the nanoparticles improved the surface protein adsorption of the nanoparticle, a condition which the nanoparticles would largely experience in vitro and in vivo and hence improve their cellular internalization. Spherical, homogenous IDA nanoparticles (214 ± 5 nm) with surface modified by ptPVA were formulated using the solvent emulsification-diffusion technique. The encapsulation efficiency and drug loading amounted around 85%. In vitro release studies indicated a controlled release of IDA. Safety and efficacy of the nanoparticles was confirmed by suitable cellular cytotoxicity assays. Protein binding studies indicated a higher adsorption of the model protein on nanoparticles formulated with ptPVA as compared to PVA. Cellular uptake studies by confocal laser scanning microscopy revealed a higher cellular uptake of ptPVA stabilized nanoparticles thus confirming the proposed hypothesis of higher protein adsorption being responsible for higher cellular internalization.

Noninvasive in vivo monitoring of the biofate of 195 kDa poly(vinyl alcohol) by multispectral fluorescence imaging.

A comprehensive knowledge of the in vivo fate of polymers is essential for their potential application in humans. In this study, the body distribution, accumulation, and elimination processes of intraperitoneally (ip) administered poly(vinyl alcohol) (PVA) in mice were investigated in detail. Two derivatives of PVA (195 kDa) having covalently bound fluorescent dye labels were synthesized and used to follow PVA in vivo by noninvasive multispectral fluorescence imaging over several months. Detailed ex vivo fluorescence imaging was performed additionally and combined with tissue accumulation studies using confocal microscopy. Filtration and confocal imaging at appropriate synthetic membranes, used as models for glomerular filtration, confirmed a considerable PVA permeation. This investigation yields new scientific findings about the fate of PVA in vivo. PVA accumulated in fat tissue at high levels, which suggests that PVA is suitable not only for abdominal surgeries but also for controlled release applications after ip or subcutaneous injection.

Treatment of advanced emphysema with emphysematous lung sealant (AeriSeal®).

BACKGROUND: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. OBJECTIVES: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. METHODS: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. RESULTS: Treatment was well tolerated. There were no treatment-related deaths (i.e., within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = -7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV(1)) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = -1.0 ± 1.04 units; change in St. George's Respiratory Questionnaire (ΔSGRQ) score = -9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = -0.5 ± 6.4%; ΔFEV(1) = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = -2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = -6.7 ± 7.0 units). CONCLUSIONS: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.