Polyelectrolyte-coated liposomes microfluidically assembled in one-step for enhancing cell endocytosis and in-vivo immune responses.

To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6 mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities.

Current Progress of Platelet-Rich Derivatives in Cartilage and Joint Repairs.

In recent years, several types of platelet concentrates have been investigated and applied in many fields, particularly in the musculoskeletal system. Platelet-rich fibrin (PRF) is an autologous biomaterial, a second-generation platelet concentrate containing platelets and growth factors in the form of fibrin membranes prepared from the blood of patients without additives. During tissue regeneration, platelet concentrates contain a higher percentage of leukocytes and a flexible fibrin net as a scaffold to improve cell migration in angiogenic, osteogenic, and antibacterial capacities during tissue regeneration. PRF enables the release of molecules over a longer period, which promotes tissue healing and regeneration. The potential of PRF to simulate the physiology and immunology of wound healing is also due to the high concentrations of released growth factors and anti-inflammatory cytokines that stimulate vessel formation, cell proliferation, and differentiation. These products have been used safely in clinical applications because of their autologous origin and minimally invasive nature. We focused on a narrative review of PRF therapy and its effects on musculoskeletal, oral, and maxillofacial surgeries and dermatology. We explored the components leading to the biological activity and the published preclinical and clinical research that supports its application in musculoskeletal therapy. The research generally supports the use of PRF as an adjuvant for various chronic muscle, cartilage, and tendon injuries. Further clinical trials are needed to prove the benefits of utilizing the potential of PRF.

Fabrication of versatile poly(xylitol sebacate)-co-poly(ethylene glycol) hydrogels through multifunctional crosslinkers and dynamic bonds for wound healing.

Poly(polyol sebacate) (PPS) polymer family has been recognized as promising biomaterials for biomedical applications with their characteristics of easy production, elasticity, biodegradation, and cytocompatibility. Poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG) has been developed to fabricate PPS-based hydrogels; however, current PXS-co-PEG hydrogels presented limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. Here, we fabricate a new type of PXS-co-PEG hydrogels through the use of multifunctional crosslinkers as well as dynamic bonds. In our design, polyethyleneimine-polydopamine (PEI-PDA) macromers are utilized to crosslink aldehyde-functionalized PXS-co-PEG (APP) through imine bonds and hydrogen bonds. PEI-PDA/APP hydrogels present multiple functional properties (e.g., fluorescent, elastomeric, biodegradable, self-healing, bioadhesive, antioxidant, and antibacterial behaviors). These properties of PEI-PDA/APP hydrogels can be fine-tuned by changing the PDA grafting degrees in the PEI-PDA crosslinkers. Most importantly, PEI-PDA/APP hydrogels are considered promising wound dressings to promote tissue remodeling and prevent bacterial infection in vivo. Taken together, PEI-PDA/APP hydrogels have been demonstrated as versatile biomaterials to provide multiple tailorable properties and desirable functions to expand the utility of PPS-based hydrogels for advanced biomedical applications. STATEMENT OF SIGNIFICANCE: Various strategies have been developed to fabricate poly(polyol sebacate) (PPS)-based hydrogels. However, current PPS-based hydrogels present limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. This work describes that co-engineering crosslinkers and interfacial crosslinking is a promising approach to synthesizing a new type of poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG) hydrogels as multifunctional hydrogels to expand the utility of PPS-based hydrogels for advanced biomedical applications. The fabricated hydrogels present multiple functional properties (e.g., fluorescent, biodegradable, elastomeric, self-healing, bioadhesive, antioxidative, and antibacterial), and these properties can be fine-tuned by the defined crosslinkers. The fabricated hydrogels are also used as promising wound dressing biomaterials to exhibit promoted tissue remodeling and prevent bacterial infection in vivo.

Transformation of theranostic alginate-based microbubbles from raspberry-like to core-shell-like microbubbles and in vitro studies.

In this study alginate-based microbubbles with a raspberry-like or core-shell-like morphology and with an average particle size of 553.6 ± 69.6 µm were synthesized; this was done through a novel procedure of transforming the structure with a 40 kHz ultrasonication which also stimulated the release of the components inside. Through the use of the electrospray technique in conjunction with agitation processes, components such as shikonin (SHK) and indocyanine green (ICG) were simultaneously encapsulated in alginate microbubbles to produce SHK-ICG alginate microbubbles; these microbubbles had half-maximal inhibitory concentrations of approximately 2.08 and 4.43 µM toward CP70 and SKOV3 ovarian cancer-cell lines, respectively, in an in vitro cell model. Moreover, these SHK-ICG alginate microbubbles enhanced brightness by 2.5 fold in ultrasound imaging relative to CaCl2 medium only. In conclusion, SHK-ICG alginate microbubbles have promise for use in theranostics.

The Study of 3D Printing-Assisted Electrospinning Technology in Producing Tissue Regeneration Polymer-Fibroin Scaffold for Ureter Repair.

OBJECTIVE: Long segment ureteral lesion with obstruction is a clinically difficult issue for recovering and maintaining organ or tissue function. Regeneration medicine using various biomaterials as a scaffold in supporting tissue regrowth is emerging. We developed this customized scaffold using electrospinning and 3-dimensional assistance and expected that it may provide an alternative biomaterial for ureter defect repair. MATERIAL AND METHODS: Our study synthesized polycaprolactone and silk fibroin combination as biomaterial scaffolds. The differences in physicochemical properties and biocompatibility of polycaprolactone-silk fibroin bio-scaffolds prepared by electrospinning alone and 3-dimensional printing combined with electrospinning in proper ratios were compared and characterized. SV-HUC-1 uroepithelial cells cultured in polycaprolactone-silk fibroin (4 : 6) scaffolds were observed under a scanning electron microscope and using calcein-acetomethoxy and propidium iodide stain. The ex vivo resected healthy human ureteral segment tissue was anastomosed with the polycaprolactone-silk fibroin scaffolds and cultured in an ex vivo bath for 2 weeks. The cellular growth on the polycaprolactone-silk fibroin scaffold was observed microscopically. In the New Zealand white rabbit model, we performed a 1/5 ratio (2 cm out of 10 cm) defect replacement of the unilateral ureter. After 7 weeks, the rabbits were sacrificed and the implanted ureter scaffolds were resected for tissue sectioning and the cellular growth was observed by hematoxylin and eosin and Masson staining. RESULTS: When the proportion of silk fibroin was increased and the 3-dimensional electrospinning method was used, both the size and diameter of nanofiber holes were increased in the polycaprolactone-silk fibroin scaffold. Scanning electron microscope and fluorescent stain revealed that cultured 3T3 and SV-HUC-1 uroepithelial cells could electively penetrate inside the polycaprolactone-silk fibroin (4 : 6) nanofibrous scaffolds in 3 days. The polycaprolactone-silk fibroin scaffold anastomosis in an ex vivo bath showed cellular growth stably along the scaffold for 2 weeks, and most of the cells grow along with the outboard of the scaffold in layers. In an animal model, different layered cells can be observed to grow along with the outboard of the scaffold with mucosa, submucosa, muscular layer, and the serosa layer order after 7 weeks. Mucosa and muscular layer growth along the scaffold inner wall were seen simultaneously. CONCLUSION: 3-dimensional electrospinning synthesized 4 : 6 polycaprolactone-silk fibroin nanofiber scaffolds that are feasible for tissue growth and achieve the purpose of ureteral reconstruction in animal experiments. This new form of 3-dimensional electrospinning constructed polycaprolactone-silk fibroin nanofiber scaffold may be considered as a clinical urinary tract tissue reconstruction alternative in the future.

The Role of Aldehyde-Functionalized Crosslinkers on the Property of Chitosan Hydrogels.

Chitosan has been utilized as a popular biopolymer to fabricate hydrogels for biomedical applications. However, chitosan hydrogels are generally too brittle to mimic the deformability of the extracellular matrix in many tissues and organs. In particular, the role of the varied crosslinkers in determining the elasticity of chitosan hydrogels is lack of discussion. Here, three aldehyde-functionalized crosslinkers (i.e., aldehyde-modified poly(xylitol sebacate)-co-poly(ethylene glycol) (APP), glutaraldehyde (GA), and polydextran aldehyde (PDA)) are used to react with quaternized chitosan (QCS) through imine bonds to form hydrogels. The microstructures, mechanical performances, and cytocompatibility of the three hydrogels are systematically investigated. The APP/QCS hydrogels presented the best compressive and stretch properties among the three hydrogels. The mechanical property and antibacterial activity of APP/QCS hydrogels can be further modulated using varied QCS amounts, where more QCS contributed higher stiffness and stretchability as well as better bacterial inhibition to the APP/QCS hydrogels. Taken together, it is demonstrated that the inherent elastomeric characteristic of APP crosslinker provides the desirable elasticity and stretchability to QCS hydrogels compared to the other aldehyde-functionalized crosslinkers of GA and PDA. This strategy of using multivalent elastomeric crosslinkers to fabricate deformable chitosan hydrogels can expand the use of chitosan hydrogels in tissue engineering applications.

Gallic Acid-Containing Gelatin-Based Nonwoven Mat with Synergistic Photodegradation and Photoindication Function for Reducing Nicotine.

Cigarette smoking is a popular habit that has negative health consequences for populations. In this study, we developed a gallic acid-containing, gelatin-based nonwoven mat with photodegradation and photoindication functions. This could react with sidestream cigarette smoke and simultaneously inhibit the activity of the microbe growth in the air. The results of a fluorescence emission spectrum evidenced this photoindication function. Neither the nicotine nor gallic acid showed a redshift emission spectrum. However, the emission spectrum of the nonwoven mat exhibited the redshift and increased in intensity after absorbing the sidestream cigarette smoke. In this spectral evidence, the natural polymer played a key role in the photoindication function's display because it could dissolve the nicotine of the sidestream cigarette smoke and cause it to react with the gelatin structure. The high performance liquid chromatography-mass spectroscopy results indicated that the gallic acid and ultraviolet (UV) light enhanced the absorption of nicotine and nicotine-like derivatives, which were dissolved by the Tween 80 of nonwoven mat. The liquid paraffin and Tween 80 could oxidize, dehydrogenate, and demethylate the nicotine that was absorbed by the gelatin nonwoven mat. In conclusion, the nonwoven mat developed in this study provided the functions to filter the nicotine of sidestream smoke and activate the photoindication property by absorbing 365-nm UV light.

Plate-like Alginate Microparticles with Disulfiram-SPIO-Coencapsulation: An In Vivo Study for Combined Therapy on Ovarian Cancer.

Disulfiram is a drug used to support the treatment of chronic alcoholism. Recently, it has been found to have an off-label ability to inhibit the growth of ovarian cancer cells. However, the original formulation was designed for use via oral administration, which is not suitable to be given by a direct spray on the affected area. Therefore, in this study, we designed and prepared alginate (ALG) microparticles loaded with disulfiram and superparamagnetic iron oxide (cross-linking disulfiram/SPIO/ALG MPs), which have great potential application for inhibiting the growth of ovarian cancer simultaneously via two treatments, i.e., chemotherapy and hyperthermia. The drug-encapsulating alginate microparticles were prepared using an electrospray system and then cross-linked with calcium chloride ions. The particles were observed by optical microscopy and scanning electron microscopy, and found to be approximately 200 µm in diameter. The disc-shape morphology of the microparticles could be controlled by up to 95%. The drug-encapsulation efficiency of the microparticles reached 98%, and the suppression of tumor growth for the free-form disulfiram-treated group and disulfiram/SPIO/ALG MPs-treated group were 48.2% and 55.9% of tumor volume reduction, respectively, compared with a cisplatin-treated group. A hyperthermic effect can be achieved by applying a magnetic field to oscillate SPIO. The results of this study showed that these cross-linking disulfiram/SPIO/ALG MPs are potential drug carriers for the treatment of ovarian cancer.

Evaluation of Polyacrylonitrile Nonwoven Mats and Silver-Gold Bimetallic Nanoparticle-Decorated Nonwoven Mats for Potential Promotion of Wound Healing In Vitro and In Vivo and Bone Growth In Vitro.

We prepared polyacrylonitrile (PAN) and urchin-like Ag-Au bimetallic or Ag nanoparticle-decorated PAN nonwoven mats using electrospinning and evaluated them in vitro and in vivo for wound healing, antibacterial effects on skin tissue, and promotion of bone ingrowth in vitro. A facile, green, low-temperature protocol was developed to obtain these nonwoven mats. The sterilization rate of urchin-like Ag-Au bimetallic and Ag nanoparticle-decorated PAN nonwoven mats against Staphylococcus aureus was 96.81 ± 2.81% and 51.90 ± 9.07%, respectively, after 5 h treatment. In an in vitro cell model, these two mats did not show significant toxicity; cell viability of >80% was obtained within 5 h of treatment. In vivo animal model preclinical assessment showed that the urchin-like Ag-Au bimetallic nonwoven mat group showed significant wound recovery because of sebaceous gland, hair follicle, and fat formation during skin tissue regeneration; increased neovascularization and compact collagen fibers were observed in the dermal layer, comparable to the findings for the control group. The mother substrate of the urchin-like Ag-Au bimetallic nanoparticle-decorated PAN nonwoven mats, that is, pure PAN nonwoven mats, was found to be a potential scaffold for bone tissue engineering as osteoblast ingrowth from the top to the bottom of the membrane and proliferation inside the membrane were observed. The key genetic factor Cbfa1 was identified as a key osteoblast differentiation regulator in vitro. Thus, electrospun membrane materials show potential for use as dual-functional biomaterials for bone regeneration and infection control and composite grafts for infectious bone and soft tissue defects.

Preclinical studies of non-stick thin film metallic glass-coated syringe needles.

Our objective in this study was to determine the biocompatibility and hemocompatibility of thin film metallic glass (TFMG) and its potential use in hypodermic needles for intramuscular or intravenous injection. Mouse and rabbit models were employed under approval from the Institutional Animal Care and Use Committee (n = 5/group, two groups in total for both animal models). Platelet-rich plasma (PRP) was collected from the whole blood of rabbits (ear vein) without anti-coagulant for use in in vitro coagulation tests. Histological analysis and optical microscopy were used to assess the endothelial structure of the inner lining of veins after being punctured with needles and detained for 3 days. Histological analysis of ear vein sections revealed that the extent of endothelial damage after puncturing with a TFMG-coated needle was 33% less than that produced by bare needles. Our results confirm that the deposition of a thin TFMG layer (e.g., Zr53Cu33Al9Ta5) on the surface of hypodermic needle can have remarkably clinical benefits, including anti-adhesion, reduced invasion, and minimal endothelial damage. Our results also confirm the good biocompatibility and hemocompatibility of the TFMG coatings.

Cytokine and Growth Factor Delivery from Implanted Platelet-Rich Fibrin Enhances Rabbit Achilles Tendon Healing.

Tendons are hypocellular and hypovascular tissues, and thus, their natural healing capacity is low. In this study, we sought to evaluate the efficacy of platelet-rich fibrin (PRF) to serve as a bioactive scaffold in promoting the healing of rabbit Achilles tendon injury. For in vitro study, the essence portion of PRF was determined through bioluminescent assay. Furthermore, we analyzed the time-sequential cytokines-release kinetics of PRF and evaluated their effects on tenocytes proliferation and tenogenic gene expressions. In animal study, the rabbit Achilles tendon defect was left untreated or implanted with normal/heat-denatured PRF scaffolds. Six weeks postoperatively, the specimens were evaluated through sonographic imaging and histological analysis. The results revealed significantly more activated platelets on bottom half of the PRF scaffold. Cytokine concentrations released from PRF could be detected from the first hour to six days. For the in vitro study, PRF enhanced cell viability and collagen I, collagen III, tenomodulin, and tenascin gene expression compared to the standard culture medium. For in vivo study, sonographic images revealed significantly better tendon healing in the PRF group in terms of tissue echogenicity and homogeneity. The histological analysis showed that the healing tissues in the PRF group had more organized collagen fiber, less vascularity, and minimal cartilage formation. In conclusion, bioactive PRF promotes in vitro tenocytes viability and tenogenic phenotypic differentiation. Administration of a PRF scaffold at the tendon defect promotes tissue healing as evidenced by imaging and histological outcomes.

CD133 Targeted PVP/PMMA Microparticle Incorporating Levamisole for the Treatment of Ovarian Cancer.

Levamisole (LEVA) is used to treat worm infections, but it can also inhibit cancer cell growth by inhibiting the aldehyde dehydrogenase pathway. Therefore, here, we developed a drug carrier targeting CD133, a biomarker overexpressed in ovarian cancer cells. The particle structure and cytotoxicity of the prepared LEVA-containing particles-called LEVA/PVP/PMMA microparticles (MPs) (because it used matrix material polyvinylpyrrolidone (PVP) and poly(methylmethacrylate) (PMMA))-were investigated in the ovarian cancer cell lines SKOV-3 and CP70. The particle size of the MPs was determined to be 1.0-1.5 µm and to be monodispersed. The hydrophilic property of PVP created a porous MP surface after the MPs were soaked in water for 20 min, which aided the leaching of the hydrophilic LEVA out of the MPs. The encapsulation efficiency of LEVA/PVP/PMMA MPs could reach up to 20%. Free-form LEVA released 50% of drugs in <1 h and 90% of drugs in 1 day, whereas the drug release rate of LEVA/PVP/PMMA MPs was much slower; 50% released in 4 h and only 70% of drugs released in 1 day. In the in vitro cell model test, 5 mM free-form LEVA and 0.1 g/mL CD133 targeted LEVA/PVP/PMMA MPs reduced SKOV-3 cell viability by 60%; 0.1 g/mL LEVA/PVP/PMMA MPs was equivalent to a similar dosage of the free drug. In addition, the cytotoxicity of CD133-conjugated LEVA/PVP/PMMA MPs shows a different cytotoxicity response toward cell lines. For SKOV-3 cells, treatment with free-form LEVA or CD133-conjugated LEVA/PVP/PMMA MPs exerted dose-dependent cytotoxic effects on SKOV-3 cell viability. However, CD133-conjugated LEVA/PVP/PMMA MPs demonstrated no significant dose-dependent cytotoxic efficacy toward CP70 cells.

Direct Visualization and Semi-Quantitative Analysis of Payload Loading in the Case of Gold Nanocages.

Upon incubation with Au nanocages, pyrrole (Py) molecules can enter the cavities by diffusing through the porous walls and then be polymerized to generate a polypyrrole (PPy) coating on the inner surface. The thicknesses of the PPy coating can serve as a direct indicator for the amount of Py molecules that diffuse into the cavity. Py molecules are able to diffuse into the cavities throughout the polymerization process, while a prolonged incubation time increases the amount of Py accumulated on both inner and outer surfaces of the nanocages. Furthermore, it is demonstrated that the dimensions of the cavity and the size of the pores in the wall are not critical parameters in determining the loading efficiency, as they do not affect the thickness of the PPy coating on the inner surface. These findings offer direct evidence to support the applications of Au nanocages as carriers for drug delivery and controlled release.

Evaluation of Chitosan Derivative Microparticles Encapsulating Superparamagnetic Iron Oxide and Doxorubicin as a pH-Sensitive Delivery Carrier in Hepatic Carcinoma Treatment: An in vitro Comparison Study.

We developed a novel, pH-sensitive drug delivery microparticle based on N-palmitoyl chitosan (NPCS) to transport the superparamagnetic iron oxide (SPIO) and anticancer drug doxorubicin (DOX). The characteristics of NPCS were characterized through nuclear magnetic resonance. Our results based on testing of volume swelling in multiple pH aqueous solutions revealed that the modified chitosan had a pH-sensitive property. The morphology and size of the DOX-SPIO/NPCS microparticles were investigated using transmission electron microscopy and scanning electron microscopy. The statistical result of microparticles had diameter of 185 ± 87 nm. Surface chemical moieties of DOX-SPIO/NPCS microparticles were confirmed using attenuated total reflection Fourier transform infrared spectroscopy and indicated the existence of mostly hydrophilic groups such as -OH, -C=O, and -C-O-C-. Transmission electron microscopy revealed the dark contrast of SPIO dots encapsulated in the NPCS matrix. Nuclear magnetic resonance T2-weighted magnetic resonance imaging confirmed that the produced DOX-SPIO/NPCS microparticles still exhibited T2 relaxation durations as short as 37.68 ± 8.69 ms (under administration of 2.5 µg/mL), which is comparable to the clinically required dosage. In the drug release profile, the DOX-SPIO/NPCS drug delivery microparticle was accelerated in an acidic environment (pH 6.5) compared with that in a basic environment. Microparticles in a cytotoxicity assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) revealed that DOX-SPIO/NPCS microparticles had better antitumor ability than did free-form of DOX. Additionally, microparticles loaded with 0.5-5 µg/mL DOX in an acidic environment (pH 6.5) demonstrated higher efficacy against Hep G2 cell growth, possibly because of the swelling effect of NPCS, resulting in volume expansion and easy drug release. Accordingly, these large DOX-SPIO/NPCS microparticles showed potential for application as a pH-sensitive drug delivery system and as chemoembolization particles for hepatic carcinoma therapy.

Relationships of Age and Sex with Cytokine Content and Distribution in Human Platelet Fibrin Gels.

We aimed to determine relationships between age and sex with cytokine content and distribution in human platelet-rich fibrin (PRF) gel. Rabbit PRF was harvested from whole blood (n = 6). Human PRF was collected from 36 healthy volunteers (1:1 men:women) without systemic diseases and not current undergoing medical treatment. Histological analysis and optical microscopy were used to assess the three-dimensional structure of the PRF network. Enzyme-linked immunosorbent assays, quantification of adenosine triphosphate, and bioluminescence imaging of PRF sections were used to assess cytokine and entrapped platelet distribution. Three-dimensional structures of fibrin networks revealed concentration gradients of the platelet-derived growth factor beta beta homodimer and the transforming growth factor-beta 1. Histological analysis of PRF sections (from the red blood cell end to the plasma end of a clot) showed a gradual increase in average porosity, most prominently in PRF clots from young and middle-aged men and women, and a decrease in compactness along the longitudinal axis of the PRF gel. The end of the PRF gel closest to the red blood cell layer is the essence of the PRF clot, and the ability to generate platelets depends on sex and age in humans.

Is Heart Failure Associated With Risk of Suicide?

BACKGROUND: The high prevalence of heart failure (HF) in developed countries imposes a substantial burden on health care resources. Depression is widely recognized as a risk factor associated with HF. This study examined the relationship between suicide and HF after controlling for depression and other comorbidities. METHODS AND RESULTS: The population comprised 52,749 adult patients who died from suicide from 2000 to 2012 and 210,996 living control subjects matched by age, sex, and residence area. Data were obtained from the Health and Welfare Data Science Center, Taiwan. Multivariable models were constructed to evaluate the relationship between HF and suicide. In the case and control groups 1624 (3.08%) and 4053 (1.92%) patients had HF, respectively, indicating that HF was associated with an increased risk of suicide (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.59-1.79). The risk of suicide was highest during the initial 6 months after HF (adjusted OR 7.04, 95% CI 5.37-9.22) and subsequently declined gradually. Among psychiatric disorders, mood disorders (adjusted OR 7.42, 95% CI 7.06-7.79) yielded the highest odds of suicide. CONCLUSIONS: The risk of suicide is higher for patients with HF than for healthy individuals without HF. This risk is particularly high during the first 6 months after HF diagnosis. This study provides strong evidence that depression is a negative prognostic factor for patients with HF and increases the risk of suicide. The results suggest that early screening and treatment for depression and suicide risk should be conducted for patients with HF.

Evaluation of a series of silk fibroin protein-based nonwoven mats for use as an anti-adhesion patch for wound management in robotic surgery.

A novel anti-adhesion nonwoven mat mainly composed of silk fibroin protein (SFP) was fabricated via the single-spinneret electrospinning technique. A series of SFP-based electrospun nonwoven mats containing additives of different synthetic polymer ratios, such as pure SFP, SFP/poly(vinyl alcohol) (PVA), SFP/polyethylene glycol (PEG), and SFP/polyethylene oxide (PEO) were produced and compared. All membranes were porous and had diameters of 324.02 ± 113.7, 308.86 ± 74.02, 366.22 ± 115.81, and 341.82 ± 119.42 nm, respectively. The average pore size for each membrane was 1.132 ± 0.99, 0.811 ± 0.424, 0.975 ± 0.741, and 0.784 ± 0.497 µm2 . No nonwoven mats showed significant cytotoxicity toward fibroblast cells based on the results of MTT assays. Surprisingly, for all groups of SFP-based nonwoven mats, nitrate formation was reduced by up to 94.55 ± 14.50%, 92.16 ± 19.38%, 91.28 ± 28.375%, and 92.00 ± 12.64% in lipopolysaccharide-induced RAW 264.7 macrophages model. Tissue anti-adhesion potential was evaluated in an in vitro fibroblast cell adhesion model and in vivo wounded mice model. In vitro, the mean cell anti-adhesion percentage of fibroblast cells changed over time in the following order: PVA/SFP > SFP > PEG/SFP∼PEO/SFP. In vivo, SFP and PVA/SFP-treated groups both showed superior collagen regeneration and wound closure. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 221-230, 2018.

Facilitating In Vivo Articular Cartilage Repair by Tissue-Engineered Cartilage Grafts Produced From Auricular Chondrocytes.

BACKGROUND: Insufficient cell numbers still present a challenge for articular cartilage repair. Converting heterotopic auricular chondrocytes by extracellular matrix may be the solution. HYPOTHESIS: Specific extracellular matrix may convert the phenotype of auricular chondrocytes toward articular cartilage for repair. STUDY DESIGN: Controlled laboratory study. METHODS: For in vitro study, rabbit auricular chondrocytes were cultured in monolayer for several passages until reaching status of dedifferentiation. Later, they were transferred to chondrogenic type II collagen (Col II)-coated plates for further cell conversion. Articular chondrogenic profiles, such as glycosaminoglycan deposition, articular chondrogenic gene, and protein expression, were evaluated after 14-day cultivation. Furthermore, 3-dimensional constructs were fabricated using Col II hydrogel-associated auricular chondrocytes, and their histological and biomechanical properties were analyzed. For in vivo study, focal osteochondral defects were created in the rabbit knee joints, and auricular Col II constructs were implanted for repair. RESULTS: The auricular chondrocytes converted by a 2-step protocol expressed specific profiles of chondrogenic molecules associated with articular chondrocytes. The histological and biomechanical features of converted auricular chondrocytes became similar to those of articular chondrocytes when cultivated with Col II 3-dimensional scaffolds. In an in vivo animal model of osteochondral defects, the treated group (auricular Col II) showed better cartilage repair than did the control groups (sham, auricular cells, and Col II). Histological analyses revealed that cartilage repair was achieved in the treated groups with abundant type II collagen and glycosaminoglycans syntheses rather than elastin expression. CONCLUSION: The study confirmed the feasibility of applying heterotopic chondrocytes for cartilage repair via extracellular matrix-induced cell conversion. CLINICAL RELEVANCE: This study proposes a feasible methodology to convert heterotopic auricular chondrocytes for articular cartilage repair, which may serve as potential alternative sources for cartilage repair.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin.

OBJECTIVES:: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-ß1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS:: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS:: Cytokines platelet-derived growth factor-BB and transforming growth factor-ß1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION:: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.