Use of the Indigo CAT RX aspiration system during percutaneous coronary intervention.

BACKGROUND: The use of the Indigo CAT RX Aspiration System (Penumbra Inc.) during percutaneous coronary intervention has received limited study. METHODS: We retrospectively examined the clinical, angiographic, and procedural characteristics, outcomes, and follow-up of patients who underwent mechanical aspiration thrombectomy with the Indigo CAT RX system (Penumbra Inc.) at a large tertiary care hospital between January 2019 and April 2023. RESULTS: During the study period, 83 patients (85 lesions) underwent thrombectomy with the Indigo CAT RX. Mean patient age was 64.9 ± 14.48 years and 31.2% were women. The most common presentations were ST-segment elevation myocardial infarction (MI) (66.2%) and non-ST-segment elevation MI (26.5%). A final thrombolysis in MI flow grade of 3 and final myocardial blush grade of 3 were achieved in 76% and 46% of the cases, respectively. Technical success was achieved in 88.9% of the cases that included Indigo CAT RX treatment only, compared with 57.1% of the cases that also included manual aspiration. There were no device-related serious adverse events. At 30-day postprocedure, the incidence of major adverse cardiac events (composite of cardiovascular death, recurrent MI, cardiogenic shock, new or worsening New York Heart Association Class IV heart failure, stroke) was 8.5%: 1.3% stroke (postprocedure, in-hospital), 1.3% MI, 6.1% cardiac death, and 7.5% developed cardiogenic shock. CONCLUSIONS: Use of the Indigo CAT RX system is associated with high technical success and acceptable risk of complications, including stroke.

Promoting chondrocyte cell clustering through tuning of a poly(ethylene glycol)-poly(peptide) thermosensitive hydrogel with distinctive microarchitecture.

Hydrogels are considered to be attractive cell-matrix for chondrocytes due to their similarity in properties to the natural cartilage. However, the formation of chondrocyte cell clusters in hydrogels has been mostly limited to naturally-derived or relatively fast degrading materials. In this study, a series of diblock copolymer poly(ethylene glycol)-poly(alanine) (mPEG-PA) was synthesized and investigated as injectable biomimic hydrogels for the culturing of chondrocytes. Depending on the poly(alanine) chain length, afforded hydrogels exhibited variable mechanical property and microarchitecture due to difference in secondary structure arrangement. After 21days of culture, cell clusters were observed in all hydrogels with longer PA chains and these hydrogels supported more homogenous and established clustering as well as significantly higher glycosaminoglycan and collagen deposition. Interestingly, scanning electron microscopy revealed a distinct micron range fibrillar-like microarchitecture that may be responsible for maintaining chondrocyte phenotype and matrix production. In addition, micrographs revealed the presence of collagen fibrils and an extensive extracellular matrix network. Therefore, it is reasonable to conclude that mPEG-PA hydrogels possess the desirable properties for chondrocyte cluster formation and serve as potential candidate in cartilage tissue engineering.

A hydrolytically-tunable photocrosslinked PLA-PEG-PLA/PCL-PEG-PCL dual-component hydrogel that enhances matrix deposition of encapsulated chondrocytes.

In this study, a series of photocrosslinked hydrogels were designed composed of both poly(lactide)-poly(ethylene glycol)-poly(lactide) (PEL) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PEC) macromers. The PEL/PEC hydrogels at ratios of 100:0, 75:25, 50;50, 25:75 and 0:100 were studied for their degradation characteristics and their ability to support chondrogenesis of encapsulated chondrocytes. Difference in hydrolytic susceptibility between copolymers led to different degradation patterns where higher PEC content correlated with slower degradation. Increased chondrogenic gene expression was observed in chondrocyte-laden hydrogels within a 4-week culture period. Biochemical and histological evaluations revealed significant accumulation of extracellular matrix proteins such as glycosaminoglycans and collagen in the 50/50 hydrogel owing to appropriate tuning of hydrogel degradation. These results demonstrate that the dual-component photocrosslinked hydrogel system is suitable for use as scaffold to support chondrogenesis and, moreover, the tunability of these systems opens up possibilities for use in different cell culturing applications. Copyright © 2014 John Wiley & Sons, Ltd.

Controlled release of strontium through neutralization reaction within a methoxy(polyethylene glycol)-polyester hydrogel.

BACKGROUND: The aim of this study was to develop a minimally invasive hydrogel system that can release strontium ions, an element that has been shown to increase osteoblast proliferation and prohibit bone resorption, in a controlled manner. METHODS: SrCO3 was selected as the salt of choice due to potential acid neutralization reaction between SrCO3 and degradation by-products of methoxy(polyethylene glycol)-co-poly(lactic-co-glycolic acid) (mPEG-PLGA): namely, lactic acid and glycolic acid. SrCO3 was incorporated into mPEG-PLGA hydrogel, and the system was assessed for gelation properties, drug release and biocompatibility. RESULTS: SrCO3 incorporation at hydrogel to SrCO3 ratios of 5:1, 3:1 and 1:1 (wt%) did not compromise the thermosensitivity of mPEG-PLGA hydrogels. Furthermore, incorporation of SrCO3 at 1:1 ratio prevented copolymer self-catalysis and decreased hydrogel weight loss from 85% to 61% in vitro after 30 days. During the 30-day time frame, zero-order strontium release was observed and was correlated to hydrogel degradation and acidity. The addition of SrCO3 also improved in vivo hydrogel biocompatibility, due to moderation of acidic microenvironment and amelioration of inflammatory response. CONCLUSIONS: These results showed that the described system is suitable for the extended release of strontium and exhibits potential for localized treatment for osteoporosis or as a bone void filler.

A cell-compatible PEO-PPO-PEO (Pluronic®)-based hydrogel stabilized through secondary structures.

Pluronic F-127 (PF127) is a thermosensitive polymer that has been widely recognized as a potential candidate for various bio-applications. However, in hydrogel form, its rapid disintegration and inhospitality toward cells have significantly limited its usage. As a means to increase the integrity and cell compatibility of a PF127 hydrogel, we propose the introduction of stabilizing secondary structures to the gel network by the addition of secondary structure-forming oligo-alanine and oligo-phenylalanine. Results indicate that increasing the oligo(peptides) attached to PF127 led to a significant decrease in the gelation concentration and temperature. A selected oligo(peptide)-modified PF127 was capable of forming a stable hydrogel network at 5% and suffered only 20% weight loss after 7days of incubation in media. Scanning electron microscopy (SEM) revealed comparably more interconnected morphology in modified hydrogels which may be attributed to the presence of secondary structures, as verified by circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy. Nuclear magnetic resonance (NMR) provided insights into the extensive interactions at the micelle core, which is the key to altered gelation behavior. Furthermore, modified hydrogels maintained structural integrity within culturing media and supported the proliferation of encapsulated chondrocytes. In addition, in vivo residence time was extended to well beyond 2weeks after oligo(peptide) modification, thereby broadening the application scope of the PF127 hydrogel to encompass long-term drug delivery and cell culturing.

Enhancing the in vivo transdermal delivery of gold nanoparticles using poly(ethylene glycol) and its oleylamine conjugate.

In this study, we investigated the effect of (ethylene glycol) (PEG) and PEG-oleylamine (OAm) functionalization on the skin permeation property of gold nanoparticles (GNS) in vivo. Chemisorption of polymers onto GNS was verified by a red shift in the ultraviolet-visible spectrum as well as by a change in the nanoparticle surface charge. The physicochemical properties of pristine and functionalized nanoparticles were analyzed by ultraviolet-visible spectroscopy, zeta potential analyzer, and transmission electron microscopy. Transmission electron microscopy revealed that the interparticle distance between nanoparticles increased after GNS functionalization. Comparing the skin permeation profile of pristine and functionalized GNS, the follicular deposition of GNS increased twofold after PEG-OAm functionalization. Moreover, PEG- and PEG-OAm-functionalized nanoparticles were able to overcome the skin barrier and deposit in the deeper subcutaneous adipose tissue. These findings demonstrate the potential of PEG- and PEG-OAm-functionalized GNS in serving a multitude of applications in transdermal pharmaceuticals.

The effects of different molecular weight chondroitin-4-sulfates in chondrocyte pellet culture.

For this study, we cultured chondrocyte pellets in Dulbecco's modified Eagle's medium plus a 2 % fetal bovine serum medium, and treated them with 2- to 8-mer oligosaccharides of chondroitin sulfate A to examine the effects of these oligosaccharides on the differentiation and protection of chondrocytes. We found low-molecular-weight CSAs to increase the ratio of the gene expression levels of collagen II/collagen I of chondrocytes from the first day up to 14 days after culture compared with those under a CSA-free medium. Moreover, low-molecular-weight CSAs inhibited the expression of matrix metalloproteinases and peptidases, and stimulated an endogenous tissue inhibitor of metalloproteinases. The dp-8 (8-mer) CSA yielded the most effective response among promoting collagen type II protein secretions compared with other groups.

In vitro and in vivo co-culture of chondrocytes and bone marrow stem cells in photocrosslinked PCL-PEG-PCL hydrogels enhances cartilage formation.

Chondrocytes (CH) and bone marrow stem cells (BMSCs) are sources that can be used in cartilage tissue engineering. Co-culture of CHs and BMSCs is a promising strategy for promoting chondrogenic differentiation. In this study, articular CHs and BMSCs were encapsulated in PCL-PEG-PCL photocrosslinked hydrogels for 4 weeks. Various ratios of CH:BMSC co-cultures were investigated to identify the optimal ratio for cartilage formation. The results thus obtained revealed that co-culturing CHs and BMSCs in hydrogels provides an appropriate in vitro microenvironment for chondrogenic differentiation and cartilage matrix production. Co-culture with a 1:4 CH:BMSC ratio significantly increased the synthesis of GAGs and collagen. In vivo cartilage regeneration was evaluated using a co-culture system in rabbit models. The co-culture system exhibited a hyaline chondrocyte phenotype with excellent regeneration, resembling the morphology of native cartilage. This finding suggests that the co-culture of these two cell types promotes cartilage regeneration and that the system, including the hydrogel scaffold, has potential in cartilage tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

Drug Carrier for Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1-Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (¹O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier.

Parkinson's disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF) have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood-brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI) is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI) and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810). This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA) polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the polymer:DNA weight ratio of 10:1, which was 1.7-fold higher than the maximal GDNF expression of PEI1800-g-CHI/DNA. The low toxicity and high transfection efficiency of PEI600-g-CHI make it ideal for application to GDNF gene therapy, which has potential for the treatment of Parkinson's disease.

Oligoalanine-modified Pluronic-F127 nanocarriers for the delivery of curcumin with enhanced entrapment efficiency.

Curcumin is a naturally occurring compound that has been shown to have anti-oxidant, anti-inflammatory, and anti-carcinogenic activities. However, its pharmaceutical potential has been limited due to its low solubility in water. The use of amphiphilic nanocarriers is an attractive and simple method to solubilize curcumin. In this study, we modified Pluronic F-127 [poly(ethylene glycol)100-block-poly(propylene glycol)65-block-poly(ethylene glycol)100] (PF-127) with oligomers of alanine, an amino acid, to increase the drug entrapment efficiency of curcumin through core stabilization. Alanine-modified PF-127 exhibited lower critical micelle concentration and decreased molecular motion in both the hydrophilic and hydrophobic segments ((1)H NMR). Nanocarriers in the size range of 54.2-68.4 nm were observed. Entrapment efficiency of curcumin increased by at most 66% (from 25.3 to 91.3%) and the difference in solubility was clearly visualized by increased transparency of the nanocarrier solutions. Curcumin was released continuously up to 120 h from modified carriers, while drug release from unmodified carriers plateaued within 24 h. These modified nanocarriers exhibited no cytotoxicity and more efficiently delivered drugs to HeLa cells as confirmed by fluorescent microscopy. This study demonstrated that alanine modification of FDA-approved PF-127 affects copolymer nanoassembly and has a profound impact on curcumin loading and possibly on other hydrophobic drugs as well.

Evaluation of a mPEG-polyester-based hydrogel as cell carrier for chondrocytes.

Temperature-sensitive hydrogels are attractive alternatives to porous cell-seeded scaffolds and is minimally invasive through simple injection and in situ gelling. In this study, we compared the performance of two types of temperature-sensitive hydrogels on chondrocytes encapsulation for the use of tissue engineering of cartilage. The two hydrogels are composed of methoxy poly(ethylene glycol)- poly(lactic-co-valerolactone) (mPEG-PVLA), and methoxy poly(ethylene glycol)-poly(lactic- co-glycolide) (mPEG-PLGA). Osmolarity and pH were optimized through the manipulation of polymer concentration and dispersion medium. Chondrocytes proliferation in mPEG-PVLA hydrogels was observed as well as accumulation of GAGs and collagen. On the other hand, chondrocytes encapsulated in mPEG-PLGA hydrogels showed low viability and chondrogenesis. Also, mPEG-PVLA hydrogel, which is more hydrophobic, retained physical integrity after 14 days while mPEG-PLGA hydrogel underwent full degradation due to faster hydrolysis rate and more pronounced acidic self-catalyzed degradation. The mPEG-PVLA hydrogel can be furthered tuned by manipulation of molecular weights to obtain hydrogels with different swelling and degradation characteristics, which may be useful as producing a selection of hydrogels compatible with different cell types. Taken together, these results demonstrate that mPEG-PVLA hydrogels are promising to serve as three-dimensional cell carriers for chondrocytes and potentially applicable in cartilage tissue engineering.