Conbercept improves macular microcirculation and retinal blood supply in the treatment of nonischemic branch retinal vein occlusion macular edema.

PURPOSE: To investigate the effect of conbercept on macular microvascular system and retinal blood supply in the treatment of nonischemic branch retinal vein occlusion macular edema (BRVO-ME). METHODS: Patients were divided into three groups: group A (containing 12 nonischemic BRVO-ME eyes), group B (containing contralateral 12 healthy eyes), and group C (containing 30 cataract eyes to obtain normal aqueous humor cytokine levels). Group A received monthly intravitreal injections of conbercept for 3 months. General data and best-corrected visual acuity (BCVA) were compared among the three groups. Optical coherence tomography angiography (OCTA) results (including central macular thickness [CMT], retinal vascular density and perfusion, and foveal avascular zone [FAZ]) at baseline were compared among groups A and B. Aqueous humor cytokine levels (including VEGF, IL-8, PDGF-AA, TNF-α, and ANGPTL-4) at baseline were compared between groups A and C. Moreover, BCVA, OCTA results, and aqueous humor cytokine levels of group A before and after conbercept treatment were compared. RESULT: At baseline, group A had a significantly worse BCVA, lower retinal vascular density and perfusion, and numerically larger CMT and FAZ area comparing to the group B, and had a higher aqueous cytokine level (IL-8, VEGF, and ANGPTL-4) comparing to the group C (all ps < 0.05). After the injection of conbercept, group A presented a better BCVA (at initial diagnosis vs. after three conbercept injections: 1.16 ± 0.51 vs. 0.81 ± 0.30, logMAR, p < 0.05), higher retinal vascular density (11.56 ± 4.73 vs. 15.88 ± 2.31, mm-1 , p < 0.05) and perfusion (0.28 ± 0.12 vs. 0.39 ± 0.06, mm2 , p < 0.05), smaller CMT (504.92 ± 184.11 vs. 219.83 ± 46.63, mm2 , p < 0.05), as well as a lower levels of VEGF (before first injection vs. before third injection: 113.84 [70.81, 235.4] vs. 3.94 [3.56, 8.07], pg/ml, p < 0.05) and ANGPTL-4 (45,761 [7327.5, 81,402.5] vs. 25,015.5 [6690, 43,396], pg/ml, p < 0.05). However, the average FAZ area of group A expanded (at initial diagnosis vs. after three conbercept injections: 0.41 ± 0.14 vs. 0.62 ± 0.36, mm2 , p < 0.05). CONCLUSION: This study demonstrated that intraocular injection of conbercept could effectively improve macular microcirculation and increase retinal blood supply in the treatment of nonischemic BRVO-ME based on the combination of visual acuity, OCTA parameters, and aqueous humor cytokine assay results. However, further study with a larger sample size and longer observation period is still needed in the future.

A stretchable conductive Polypyrrole Polydimethylsiloxane device fabricated by simple soft lithography and oxygen plasma treatment.

This paper reports a simple method used to fabricate a stretchable conductive polypyrrole (PPy) rough pore-shape polydimethylsiloxane (p-PDMS) device. An abrasive paper is first used to imprint rough micro-structures on the SU-8 micromold. The p-PDMS microchannel is then fabricated using a standard soft-lithography process. An oxygen plasma treatment is then applied to form an irreversible sealing between the microchannel and a blank cover PDMS. The conductive layer is formed by injecting the PPy mixture into the microchannel which polymerizes in the rough pore-shape micro-structures; The PPy/p-PDMS hybrid device shows good electrical property and stretchability. The electrical properties of different geometrical designs of the PPy/p-PDMS microchannel under stretching were investigated, including straight, curved, and serpentine. Mouse embryonic fibroblasts (NIH/3 T3) were also cultured inside the PPy/p-PDMS device to demonstrate good biocompatibility and feasibility using the conductive and stretchable microchannel in cell culture microfluidics applications. Finally, cyclic stretching and bending tests were performed to evaluate the reliability of PPy/p-PDMS microchannel.

Methyl Orange removal by a novel PEI-AuNPs-hemin nanocomposite.

A novel poly(ethyleneimine)/Au nanoparticles/hemin nanocomposite (PEI-AuNPs-Hemin) acting for Methyl Orange (MO) removal has been synthesized. PEI-AuNPs was prepared firstly and it was then linked to hemin through the coupling between carboxyl groups in hemin and amino groups in PEI without the activation of carboxyl groups. The high reactivity and stability of AuNPs contributed greatly in the formation of the amido bonds in the nanocomposite. Fourier transform infrared spectroscopy, transmission electron microscopy and UV-visible spectroscopy were used to characterize the PEI-AuNPs-Hemin. Results show that PEI-AuNPs-Hemin has strong adsorption for MO. Adsorption and degradation experiments were carried out at different pHs, nanocomposite concentrations and UV irradiation times. Removal of MO in acidic solutions was more effective than in basic solutions. The real-time study showed that the MO degradation with the nanocomposite under UV irradiation was a fast process. In addition, the photocatalytic degradation mechanism was proposed. The study suggests that the PEI-AuNPs-Hemin may have promising applications in environmental monitoring and protection.

Formation of copper nanoparticles on poly(thymine) through surface-initiated enzymatic polymerization and its application for DNA detection.

Poly(thymine) (polyT) and double-stranded DNA (dsDNA) can act as efficient templates for the formation of copper nanoparticles (CuNPs) at a low concentration of CuSO4, and the formed CuNPs emit excellent fluorescence. In this work, we demonstrated a new and facile strategy for the highly sensitive and selective detection of DNA on streptavidin-functionalized magnetic beads (SA-MB) using DNA-templated CuNPs as the fluorescent probe. Target DNA (tDNA) was hybridized with the capture DNA that was immobilized on the surface of SA-MB. Surface initiated enzymatic polymerization (SIEP) was employed as the signal amplification method to generate the polyT at the 3' end of tDNA for the formation of CuNPs. The incorporation of polyT by SIEP resulted in ∼35.7 fold signal amplification compared to the dsDNA after hybridization without SIEP. A dose-response curve for detection of DNA was obtained, with a linear dynamic range of 0.1 nM to 10 nM. We showed that this method has a low pM limit of detection (LOD 98.2 pM) and it is also very sensitive to the mismatch type in a specific DNA sequence. In addition, it avoids rigorously controlled temperature, complex synthesis of the fluorescent probe and prelabeling of DNA strands and eliminates the use of sophisticated experimental techniques and equipment. Armed with these intriguing properties, the proposed system could provide an efficient tool for early diagnosis and risk assessment of malignancy.

A biomimetic enzyme modified electrode for H2O2 highly sensitive detection.

An efficient catalyst based on artificial bionic peroxidase was synthesized for electrocatalysis. A poly(ethyleneimine)/Au nanoparticle composite (PEI-AuNP) was prepared and it was then linked to hemin via a coupling reaction between carboxyl groups in hemin and amino groups in PEI without the activation of a carboxyl group by carbodiimide. Fourier transform infrared (FTIR) spectroscopy verified the formation of amido bonds within the structure. The presence of AuNPs contributed greatly in establishing the amido bonds within the composite. Transmission electron microscopy (TEM) and UV-visible spectroscopy were also used to characterize the PEI-AuNP-hemin catalyst. PEI-AuNP-hemin exhibited intrinsic peroxidase-like catalytic activities. The PEI-AuNP-hemin deposited on a glass carbon electrode had strong sensing for H2O2 with a well-defined linear relationship between the amperometric response and H2O2 concentration in the range from 1 µM to 0.25 mM. The detection limit was 0.247 nM with a high sensitivity of 0.347 mA mM(-1) cm(-2). The peroxidase-like catalytic activity of PEI-AuNP-hemin is discussed in relation to its microstructure. The study suggests that PEI-AuNP-hemin may have promising application prospects in biocatalysis and bioelectronics.

Increased serum cystatin C levels in patients with idiopathic epiretinal membrane.

CLINICAL RELEVANCE: Increased serum cystatin C may play a role in the pathogenesis of idiopathic epiretinal membrane (IERM). Physicians should be aware of this relationship and should refer patients to the ophthalmology clinic for screening. BACKGROUND: To evaluate the serum cystatin C level in patients with IERM, and its associations with visual acuity. METHODS: Sixty-eight patients with IERM and sixty-nine controls were enrolled in this cross-sectional study. Based on the results of optical coherence tomography, patients with IERM were divided into four stages (I, II, III and IV). Serum cystatin C was measured in all participants. Serum cystatin C levels were compared between the control group and IERM group and between the IERM group with different optical coherence tomography stages. Multiple linear regression was used to evaluate the relationship between serum cystatin C and IERM stages and best corrected visual acuity. RESULTS: Serum cystatin C level was higher in the IERM group than in the control group (P < 0.001). There were statistically significant differences in serum cystatin C among different stages of IERM (PI vs II = 0.011, PI vs IV < 0.001 and PIII vs IV = 0.040, respectively). There were significant differences in best corrected visual acuity among different stages of IERM (PI vs III = 0.018, PI vs IV < 0.001, PII vs IV < 0.001 and PIII vs IV < 0.001, respectively). Regression analysis showed a positive correlation between serum cystatin C and best corrected visual acuity (t = 2.238 P = 0.029). The cut-off value of receiver operation characteristic curve of serum cystatin C for IERM was 0.775. CONCLUSION: This study revealed that serum cystatin C may be involved in the pathogenesis of IERM and can predict its occurrence. Elevated serum cystatin C appears to be associated with the severity of the disease and relatively poor vision acuity in IERM patients.

Bibliometric and visual analysis of ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications from 2000 to 2023.

Background: The pathogenesis of diabetes and its microvascular complications are intimately associated with renin angiotensin system dysregulation. Evidence suggests the angiotensin converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis regulates metabolic imbalances, inflammatory responses, reduces oxidative stress, and sustains microvascular integrity, thereby strengthening defences against diabetic conditions. This study aims to conduct a comprehensive analysis of the ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications over the past two decades, focusing on key contributors, research hotspots, and thematic trends. Methods: This cross-sectional bibliometric analysis of 349 English-language publications was performed using HistCite, VOSviewer, CiteSpace, and Bibliometrix R for visualization and metric analysis. Primary analytical metrics included publication count and keyword trend dynamics. Results: The United States, contributing 105 articles, emerged as the most productive country, with the University of Florida leading institutions with 18 publications. Benter IF was the most prolific author with 14 publications, and Clinical Science was the leading journal with 13 articles. A total of 151 of the 527 author's keywords with two or more occurrences clustered into four major clusters: diabetic microvascular pathogenesis, metabolic systems, type 2 diabetes, and coronavirus infections. Keywords such as "SARS", "ACE2", "coronavirus", "receptor" and "infection" displayed the strongest citation bursts. The thematic evolution in this field expanded from focusing on the renin angiotensin system (2002-2009) to incorporating ACE2 and diabetes metabolism (2010-2016). The latter period (2017-2023) witnessed a significant surge in diabetes research, reflecting the impact of COVID-19 and associated conditions such as diabetic retinopathy and cardiomyopathy. Conclusions: This scientometric study offers a detailed analysis of the ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications, providing valuable insights for future research directions.

Development of a multifunctional bioreactor to evaluate the promotion effects of cyclic stretching and electrical stimulation on muscle differentiation.

A multifunctional bioreactor was fabricated in this study to investigate the facilitation efficiency of electrical and mechanical stimulations on myogenic differentiation. This bioreactor consisted of a highly stretchable conductive membrane prepared by depositing polypyrrole (PPy) on a flexible polydimethylsiloxane (PDMS) film. The tensile deformation of the PPy/PDMS membrane can be tuned by adjusting the channel depth. In addition, PPy/PDMS maintained its electrical conductivity under continuous cyclic stretching in the strain range of 6.5%-13% for 24 h. This device can be used to individually or simultaneously perform cyclic stretching and electrical stimulation. The results of single stimulation showed that either cyclic stretching or electrical stimulation upregulated myogenic gene expression and promoted myotube formation, where electrical stimulation improved better than cyclic stretching. However, only cyclic stretching can align C2C12 cells perpendicular to the stretching direction, and electrical stimulation did not affect cell morphology. Myosin heavy chain (MHC) immunostaining demonstrated that oriented cells under cyclic stretching resulted in parallel myotubes. The combination of these two stimuli exhibited synergetic effects on both myogenic gene regulation and myotube formation, and the incorporated electrical field did not affect the orientation effect of the cyclic stretching. These results suggested that these two treatments likely influenced cells through different pathways. Overall, the simultaneous application of cyclic stretching and electrical stimulation preserved both stimuli's advantages, so myo-differentiation can be highly improved to obtain abundant parallel myotubes, suggesting that our developed multifunctional bioreactor should benefit muscle tissue engineering applications.

Comparison of Peripheral Blood Inflammatory Indices in Patients with Neovascular Age-related Macular Degeneration and Haemorrhagic Polypoidal Choroidal Vasculopathy.

PURPOSE: To compare the differences in peripheral blood inflammatory indices between patients with neovascular age-related macular degeneration (nAMD) and haemorrhagic polypoidal choroidal vasculopathy (PCV). METHODS: Retrospective, best corrected visual acuity (BCVA), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), were analysed across the nAMD, PCV and normal control (NCG) groups of patients. The ratios' cut-off values for nAMD were calculated. RESULTS: nAMD had a significantly longer duration and better BCVA than PCV (all P < .05). The NLR, MLR and PLR were significantly higher in nAMD than in PCV and NCG (all P < .01), no significant differences between PCV and NCG (all P > .05). The ROC curve analysis revealed that the cut-off values for NLR and MLR were 1.98 and 0.24, respectively, for nAMD. CONCLUSION: NLR, MLR and PLR are significantly high in patients with nAMD. The ability of these inflammatory indicators to distinguish nAMD and PCV is unclear.

A Coupled 3d Morphological Reconstruction Approach for Surface Microcrack in Si3 n4 Ceramic Bearing Roller Based on Adaptive Nano Feature Extraction & Multiscale Depth Fusion.

To extract the fuzzy contour features, tiny depth features of surface microcracks in the Si3 N4 ceramic bearings roller. An adaptive nano feature extraction and multiscale deep fusion coupling method is proposed, to sufficiently reconstruct the three-dimensional morphology characteristics of surface microcracks. Construct an adaptive nano feature extraction method, form the surface microcrack image scale space and the Gaussian difference pyramid function equation, realize the detection and matching of global feature points. The sparse point cloud is obtained. Through polar-line correction, depth estimation, and fusion of feature points on the surface microcracks image, a multiscale depth fusion matching cost pixel function is established to realize a dense point cloud reconstruction of surface microcracks. The reconstruction results show that the highest value of the local convex surface reconstructed by the dense point cloud reaches 1183 nm, and the lowest local concave surface is accurate to 296 nm. Compared with the measurement results of the confocal platform, the relative error of the reconstruction result is 24.6%. The overall feature-matching rate of the reconstruction reaches 93.3%. It provides a theoretical basis for the study of surface microcrack propagation mechanism and the prediction of bearing life.

Use of biotinylated chitosan for substrate-mediated gene delivery.

To improve transfection efficiency of nonviral vectors, biotinylated chitosan was applied to complex with DNA in different N/P ratios. The morphologies and the sizes of formed nanoparticles were suitable for cell uptake. The biotinylation decreased the surface charges of nanoparticles and hence reduced the cytotoxicity. The loading capacities of chitosan were slightly decreased with the increase of biotinylation, but most of the DNA molecules were still complexed. Using different avidin-coated surfaces, the interaction between biotinylated nanoparticles to the substrate may be manipulated. The in vitro transfection results demonstrated that biotinylated nanoparticles may be bound to avidin coated surfaces, and the transfection efficiencies were thus increased. Through regulating the N/P ratio, biotinylation levels, and surface avidin, the gene delivery can be optimized. Compared to the nonmodified chitosan, biotinylated nanoparticles on biomaterial surfaces can increase their chances to contact adhered cells. This spatially controlled gene delivery improved the gene transfer efficiency of nonviral vectors and could be broadly applied to different biomaterial scaffolds for tissue engineering applications.

Optimization of DNA-directed immobilization on mixed oligo(ethylene glycol) monolayers for immunodetection.

The development of protein chips has suffered from problems regarding long-term protein stability and activity. We present a protein sensor surface for immunodetection that is prepared by a DNA-directed protein immobilization method on a mixed self-assembled monolayer (SAM). By this approach, an immobilized single-stranded DNA (ssDNA) surface can be transferred/modified into a protein chip by flowing in ssDNA-conjugated protein when the protein chip measurement is needed. Therefore, the long-term stability of the protein chip will not be a problem for various applications. We tried various compositions for the SAM layer, the length of the ssDNA spacer, the end-point nucleotide composition, and the processes of ssDNA immobilization of the SAM for an optimized condition for shifting the DNA chip to a protein chip. The evaluations were made by using surface plasmon resonance. Our results indicated that a 50:1 ratio of oligo(ethylene glycol) (OEG)/COOH-terminated OEG and DNA sequences with 20mer are the best conditions found here for making a protein chip via a DNA-directed immobilization (DDI) method. The designed end-point nucleotide composition contains a few guanines or cytosines, and ssDNA immobilization of the SAM by dehybridizing immobilized double-stranded DNA (dsDNA) can improve the hybridization efficiency.

Retinal hemangioblastoma in a patient with Von Hippel-Lindau disease: A case report and literature review.

Background: Retinal hemangioblastoma (RH) is a rare benign tumor and a considerable number of which are caused by Von Hippel-Lindau disease (VHL). Herein, we described a case of VHL-associated RH with retinal detachment who underwent both laser photocoagulation and vitreoretinal surgery and received satisfactory visual recovery. In addition, we reviewed the current diagnosis, genotype-phenotype association, and treatment of VHL-associated RH. Case description: A 34-year-old woman presented with vision loss in the right eye at our hospital. Fundus photography and angiography showed retinal detachment and multiple large hemangiomas in the right eye. The visual acuity improved significantly after laser photocoagulation and vitreoretinal surgery. Genetic analyses showed a p.Asn78Ser (c.233A>G) heterozygous missense mutation in the VHL gene. Conclusion: We described a rare case of VHL-associated RH and may provide a new perspective towards diagnosis and treatment of this disease. RH is one of the most common manifestations of VHL and poses a serious threat to vision. Ophthalmic examination methods include fundus examination and fundus photography, etc. The management of the disease emphasizes timely follow-up, early detection of the lesion, and the decision of treatment options according to the size, location and complications of the lesion, including ablation therapy and vitreoretinal surgery. Clinicians should strengthen the understanding of this rare disease for early detection and treatment.

Alginate/polycaprolactone composite fibers as multifunctional wound dressings.

We developed a composite wound dressing that provides multifunctional wound care. Alginate and polycaprolactone (PCL) were coelectrospun as composite fibers. Highly absorbent alginate provided a moist environment for wounds and PCL increased cell adhesion. Silver nanoparticles embedded in PCL fibers for long-term release inhibited the growth of microorganisms. In addition, plasmid DNA encoding platelet-derived growth factor-B (PDGF-B) were complexed with polyethylenimine (PEI) to form cationic nanoparticles which were then adsorbed on anionic alginate fibers through electrostatic interaction. As wound cells adhered to composite fibers, they were in situ transfected to express PDGF-B continuously. Moreover, calcium ions in alginate fibers were released into the wound site through ion exchange to accelerate hemostasis. Wound healing experiments demonstrated that PDGF-B gene-loaded composite fibers accelerated wound closure and promoted collagen formation. We expect this comprehensive study offers an ideal multifunctional solution to facilitate wound healing.

Experimental demonstration of noncontact vital-sign measurement using pulse radar.

BACKGROUD: Recently, monitoring the vital-sign with the noncontact method is a popular technology. OBJECTIVE: In this work, we present a fully pulse radar system including front-end sensing and back-end data processing. A series of ultra-wide band sensing pulses is generated and radiated to detect the subject's chest vibration which in turn obtains the required vital-sign signals. METHODS: An artificial plywood with 3 centimeter thickness is placed between a transmitting/receiving antenna of the radar and subject to demonstrate the characteristic of noncontact sensing. The firmware and digital signal processing are also presented in this paper to optimize physiological data quality. RESULTS: The experimental results show that the continuous heart rate and breathing rate can be monitored by this customized system radar module. CONCLUSION: A fully customized ultra-wide band radar for vital-sign application is presented. The radar system plan with wall parameter is also incorporated into the design consideration to meet the FCC requirement and SNR.

The Development of Polylactic Acid/Multi-Wall Carbon Nanotubes/Polyethylene Glycol Scaffolds for Bone Tissue Regeneration Application.

Composite electrospun fibers were fabricated to develop drug loaded scaffolds to promote bone tissue regeneration. Multi-wall carbon nanotubes (MWCNTs) were incorporated to polylactic acid (PLA) to strengthen electrospun nanofibers. To modulate drug release behavior, different ratios of hydrophilic polyethylene glycol (PEG) were added to composite fibers. Glass transition temperature (Tg) can be reduced by the incorporated PEG to enhance the ductility of the nanofibers. The SEM images and the MTT results demonstrated that composite fibers are suitable scaffolds for cell adhesion and proliferation. Dexamethasone (DEX), an osteogenic inducer, was loaded to PLA/MWCNT/PEG fibers. The surface element analysis performed by XPS showed that fluorine of DEX in pristine PLA fibers was much higher than those of the MWCNT-containing fibers, suggesting that the pristine PLA fibers mainly load DEX on their surfaces, whereas MWCNTs can adsorb DEX with evenly distribution in nanofibers. Drug release experiments demonstrated that the release profiles of DEX were manipulated by the ratio of PEG, and that the more PEG in the nanofibers, the faster DEX was released. When rat bone marrow stromal cells (rBMSCs) were seeded on these nanofibers, the Alizarin Red S staining and calcium quantification results demonstrated that loaded DEX were released to promote osteogenic differentiation of rBMSCs and facilitate mineralized tissue formation. These results indicated that the DEX-loaded PLA/MWCNT/PEG nanofibers not only enhanced mechanical strength, but also promoted osteogenesis of stem cells via the continuous release of DEX. The nanofibers should be a potential scaffold for bone tissue engineering application.

Electrical Field-Assisted Gene Delivery from Polyelectrolyte Multilayers.

To sustain gene delivery and elongate transgene expression, plasmid DNA and cationic nonviral vectors can be deposited through layer-by-layer (LbL) assembly to form polyelectrolyte multilayers (PEMs). Although these macromolecules can be released for transfection purposes, their entanglement only allows partial delivery. Therefore, how to efficiently deliver immobilized genes from PEMs remains a challenge. In this study, we attempt to facilitate their delivery through the pretreatment of the external electrical field. Multilayers of polyethylenimine (PEI) and DNA were deposited onto conductive polypyrrole (PPy), which were placed in an aqueous environment to examine their release after electric field pretreatment. Only the electric field perpendicular to the substrate with constant voltage efficiently promoted the release of PEI and DNA from PEMs, and the higher potential resulted in the more releases which were enhanced with treatment time. The roughness of PEMs also increased after electric field treatment because the electrical field not only caused electrophoresis of polyelectrolytes and but also allowed electrochemical reaction on the PPy electrode. Finally, the released DNA and PEI were used for transfection. Polyplexes were successfully formed after electric field treatment, and the transfection efficiency was also improved, suggesting that this electric field pretreatment effectively assists gene delivery from PEMs and should be beneficial to regenerative medicine application.

Nmur1-/- mice are not protected from cutaneous inflammation.

Neuromedin U (Nmu) is a neuropeptide expressed primarily in the gastrointestinal tract and central nervous system. Previous reports have identified two G protein-coupled receptors (designated Nmur1 and Nmur2) that bind Nmu. Recent reports suggest that Nmu mediates immune responses involving mast cells, and Nmur1 has been proposed to mediate these responses. In this study, we generated mice with an Nmur1 deletion and then profiled the responses of these mice in a cutaneous inflammation model utilizing complete Freund's adjuvant (CFA). We report here that mice lacking Nmur1 had normal inflammation responses with moderate changes in serum cytokines compared to Nmur1(+/+) littermates. Although differences in IL-6 were observed in mice lacking Nmu peptide, these mice exhibited a normal response to CFA. Our data argues against a major role for Nmur1 in mediating the reported inflammatory functions of NmU.

Gene immobilization on alginate/polycaprolactone fibers through electrophoretic deposition to promote in situ transfection efficiency and biocompatibility.

Alginate and polycaprolactone (PCL) were coelectrospun as composite nanofibers for in situ transfection, in which anionic alginate fibers were used to adsorb polyethyleneimine (PEI)/DNA polyplexes and biocompatible PCL fibers were applied to promote cell adhesion. To improve gene immobilization, direct-current electric field (DCEF) was applied to guide cationic polyplexes toward nanofibers on cathode. Fluorescent labeling experiments suggested that the applied DCEF not only accelerated but also increased the saturation levels of gene immobilization. Interestingly, these DCEF also increased the degradation of nanofibers. The water contact angle and Fourier-transform infrared spectrometry results indicated that the degraded component was mainly alginate. It suggested that the DCEF treatment may cause the electrophoresis of calcium ions to destabilize alginates fibers, and thus the degradation rates increased with the applied voltages. This alginate degradation increased the ratio of PCL in composite fibers, so the cell adhesion, viability, and proliferation were improved. Finally, these DCEF-treated fibers were used for substrate-mediated gene delivery. The transfection efficiency highly increased with DCEF when the voltages were lower than 1.5 V. This dynamic scaffold system not only provided a suitable microenvironment for cell ingrowth, but also improved gene immobilization and transfection, and thus promised its therapeutic effect for tissue regeneration.

The enrichment of cancer stem cells using composite alginate/polycaprolactone nanofibers.

Cancer stem cells (CSCs) are potential platforms to high-throughput screen anti-cancer drugs. However, they are difficult to isolate from cancer cells. Therefore, we proposed to fabricate 3-D scaffolds for CSC enrichment. Alginate is a biocompatible polysaccharide with poor cell adhesion, whereas polycaprolactone (PCL) is relative cell adhesive. These two materials were coelectrospun as composite scaffolds. Cells collected from alginate and composite fibers demonstrated high stemness, epithelial-mesenchymal transition, invasion, drug resistance, and angiogenesis. Interestingly, cells collected from composite fibers with low ratio of PCL were significantly improved their CSC properties compared to those from pure alginate fibers because few PCL fibers spatially separated cell populations to concentrate CSCs. These results suggested that alginate fibers effectively enriched CSCs and composite fibers created an uneven microenvironment to regulate cell morphology and distribution, by which cell-cell interaction was thus manipulated. These tunable scaffolds are potential to isolate CSCs from different tissues to facilitate the cancer research.