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Acute kidney injury (AKI) increases the risk of in-hospital death, adds to expense of care, and risk of early chronic kidney disease. AKI often follows an acute event such that timely treatment could ameliorate AKI and potentially reduce the risk of additional disease. Despite therapeutic success of dexamethasone in animal models, clinical trials have not demonstrated broad success. To improve the safety and efficacy of dexamethasone for AKI, we developed and characterized a novel, kidney-specific nanoparticle enabling specific within-kidney targeting to proximal tubular epithelial cells provided by the megalin ligand cilastatin. Cilastatin and dexamethasone were complexed to H-Dot nanoparticles, which were constructed from generally recognized as safe components. Cilastatin/Dexamethasone/H-Dot nanotherapeutics were found to be stable at plasma pH and demonstrated salutary release kinetics at urine pH. In vivo, they were specifically biodistributed to the kidney and bladder, with 75% recovery in the urine and with reduced systemic toxicity compared to native dexamethasone. Cilastatin complexation conferred proximal tubular epithelial cell specificity within the kidney in vivo and enabled dexamethasone delivery to the proximal tubular epithelial cell nucleus in vitro. The Cilastatin/Dexamethasone/H-Dot nanotherapeutic improved kidney function and reduced kidney cellular injury when administered to male C57BL/6 mice in two translational models of AKI (rhabdomyolysis and bilateral ischemia reperfusion). Thus, our design-based targeting and therapeutic loading of a kidney-specific nanoparticle resulted in preservation of the efficacy of dexamethasone, combined with reduced off-target disposition and toxic effects. Hence, our study illustrates a potential strategy to target AKI and other diseases of the kidney.
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Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.
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Antineoplásicos , Neoplasias , Animais , Carboplatina/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias/tratamento farmacológico , Platina/farmacologia , Platina/uso terapêuticoRESUMO
The use of chemoattractants to promote endogenous stem cell-based in situ tissue regeneration has recently garnered much attention. This study is the first to assess the endogenous stem cell migration using a newly discovered substance P (SP) analog (SP1) by molecular dynamics simulations as an efficient chemoattractant. Further, a novel strategy based on electrostatic interaction using cationic chitosan (Ch) and anionic hyaluronic acid (HA) to prepare an SP1-loaded injectable C/H formulation without SP1 loss is developed. The formulation quickly forms an SP1-loaded C/H hydrogel in situ through in vivo injection. The newly discovered SP1 is found to possess human mesenchymal stromal cells (hMSCs) migration-inducing ability that is approximately two to three times higher than that of the existing SP. The designed VEGF-mimicking peptide (VP) chemically reacts with the hydrogel (C/H-VP) to sustain the release of VP, thus inducing vasculogenic differentiation of the hMSCs that migrate toward the C/H-VP hydrogel. Similarly, in animal experiments, SP1 attracts a large number of hMSCs toward the C/H-VP hydrogel, after which VP induces vasculogenic differentiation. Collectively, these findings indicate that SP1-loaded C/H-VP hydrogels are a promising strategy to facilitate endogenous stem cell-based in situ tissue regeneration.
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Hidrogéis , Células-Tronco Mesenquimais , Animais , Humanos , Ácido Hialurônico , Células-Tronco , Substância P , Fator A de Crescimento do Endotélio VascularRESUMO
INTRODUCTION: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. MATERIALS AND METHODS: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). RESULTS: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (<1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. DISCUSSION/CONCLUSION: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.
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Dexametasona/administração & dosagem , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Audição/efeitos dos fármacos , Membrana Timpânica/efeitos dos fármacos , Animais , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Injeção Intratimpânica , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Injectable in situ-forming hydrogels have been used clinically in diverse biomedical applications. These hydrogels have distinct advantages such as easy management and minimal invasiveness. The hydrogels are aqueous formulations, and a simple injection at the target site replaces a traditional surgical procedure. Here, we review injectable in situ-forming hydrogels that are formulated by physical and chemical methods to deliver proteins and peptides. Prospects for using in situ-forming hydrogels for several specific applications are also discussed.
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Hidrogéis , Peptídeos , Proteínas , Sistemas de Liberação de Medicamentos , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Injeções , Peptídeos/administração & dosagem , Proteínas/administração & dosagemRESUMO
The use of biomimetic scaffolds for bone tissue engineering has been studied for a long time. Biomimetic scaffolds can assist and accelerate bone regeneration that is similar to that of authentic tissue, which represents the environment of cells in a living organism. Currently, numerous biomaterials have been reported for use as a biomimetic scaffold. This review focuses on the design of biomimetic scaffolds, kinds of biomaterials and methods used to fabricate biomimetic scaffolds, growth factors used with biomimetic scaffold for bone regeneration, mobilization of biological agents into biomimetic scaffolds, and studies on (pre)clinical bone regeneration from biomimetic scaffolds. Then, future prospects for biomimetic scaffolds are discussed.
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Materiais Biomiméticos , Regeneração Óssea , Osso e Ossos , Engenharia Tecidual , Alicerces Teciduais , HumanosRESUMO
To develop a biodegradable polymer possessing elasticity and flexibility, we synthesized MPEG-b-(PCL-co-PLA) copolymers (PCxLyA), which display specific rates of flexibility and elasticity. We synthesize the PCxLyA copolymers by ring-opening polymerization of ε-caprolactone and l-lactide. PCxLyA copolymers of various compositions were synthesized with 500,000 molecular weight. The PCxLyA copolymers mechanical properties were dependent on the mole ratio of the ε-caprolactone and l-lactide components. Cyclic tensile tests were carried out to investigate the resistance to creep of PCxLyA specimens after up to 20 deformation cycles to 50% elongation. After in vivo implantation, the PCxLyA implants exhibited biocompatibility, and gradually biodegraded over an eight-week experimental period. Immunohistochemical characterization showed that the PCxLyA implants provoked in vivo inflammation, which gradually decreased over time. The copolymer was used as a drug carrier for locally implantable drugs, the hydrophobic drug dexamethasone (Dex), and the water-soluble drug dexamethasone 21-phosphate disodium salt (Dex(p)). We monitored drug-loaded PCxLyA films for in vitro and in vivo drug release over 40 days and observed real-time sustained release of near-infrared (NIR) fluorescence over an extended period from hydrophobic IR-780- and hydrophilic IR-783-loaded PCxLyA implanted in live animals. Finally, we confirmed that PCxLyA films are usable as biodegradable, elastic drug carriers.
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Plásticos Biodegradáveis/química , Sistemas de Liberação de Medicamentos/efeitos adversos , Poliésteres/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Plásticos Biodegradáveis/efeitos adversos , Plásticos Biodegradáveis/síntese química , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Liberação Controlada de Fármacos , Poliésteres/efeitos adversos , Poliésteres/síntese química , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The objectives of this study are (1) to establish a ubiquitous healthcare (u-healthcare) center for those who wish to use u-healthcare, allowing them to experience the service, and (2) to evaluate the users' awareness and expectations of the service based on their overall assessment. MATERIALS AND METHODS: To establish the u-healthcare center, a kiosk, devices for health checkup, a body-type examination system, and a physical fitness assessment system were installed. Also, a u-healthcare Web site was developed. A survey was conducted on 280 individuals who visited the u-healthcare center and used the service, to determine (1) individual awareness of u-healthcare before using the service and their change of perception after use, (2) factors that affect the use of u-healthcare, and (3) the effects of disease awareness on exercise habits. RESULTS: Only 25.4% of the participants were aware of u-healthcare, and only 36% who saw the u-healthcare center recognized that it was where the u-healthcare service was provided. The group of individuals who were willing to use the u-healthcare showed statistically significant differences in their satisfaction with the overall environment of the center, as well as the specificity of the descriptions, examination results, kindness of the staff, and their responses. Additionally, the group of individuals who were diagnosed with chronic diseases and the group who were not showed statistically significant differences in the number of days on which they exercised lightly or took a walk. CONCLUSIONS: To promote the usage of u-healthcare service, the understanding of the service and the credibility of examination results need to be increased by sharing successful cases. Furthermore, to expand the use of the system that allows a person to regularly check his or her state of health, a lifelong periodical management system linked with another medical welfare program will be needed.
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Acessibilidade aos Serviços de Saúde/organização & administração , Estilo de Vida , Unidades Móveis de Saúde/organização & administração , Satisfação do Paciente/estatística & dados numéricos , Telemedicina/organização & administração , Adulto , Idoso , Conscientização , Pesquisa Empírica , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , República da Coreia , Adulto JovemRESUMO
INTRODUCTION: Studies have demonstrated that technological innovation is vital for prosperous economies, and greater technological innovation leads to improved public health indicators. The South Korean government has implemented policies to provide city services using information communication technologies, and ubiquitous healthcare (u-healthcare) wellness is one of these. This article presents the effects of using a u-healthcare center model that proves self-healthcare monitoring can work for the general population. MATERIALS AND METHODS: The u-healthcare center has provided service to the public since April 2013. It is equipped with medical devices that evaluate physiological parameters such as weight, body mass index (BMI), blood pressure (BP), pulse rate (PR), and body fat (BF). This article focuses on the analysis of BMI, BP, PR, and BF parameters. RESULTS: Health test results from 12,766 voluntary patients of the u-healthcare center were analyzed during a 1-year period. The four health parameters from each of the four seasons were analyzed and compared, showing statistically significant seasonal differences. A Duncan's post hoc analysis showed that BMI did not differ between spring and summer, whereas BP differed throughout all seasons. Participation of females was higher compared with males, and men's average BMI was statistically higher than that of the women. Some additional significant findings for all participants were as follows: 48.8% scored normal in BMI, 31.7% scored normal-controlled in BP, 90.7% scored normal in PR, and 24.8% scored normal in BF. A survey showed that 96.4% found the u-healthcare center to be generally helpful, and 95.7% responded that they would recommend it. CONCLUSIONS: Implementation of u-healthcare projects provides a new public service toward evaluating health parameters, providing historical health information access, promoting self-monitoring, and motivating users to be more aware of their own health status.
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Atenção à Saúde/métodos , Disseminação de Informação , Informática Médica/métodos , Autocuidado/métodos , Atenção à Saúde/normas , Feminino , Humanos , Masculino , Informática Médica/normas , República da Coreia , Autocuidado/normasRESUMO
OBJECTIVE: This study aimed (1) to help individuals analyze their own health status by checking their lifestyle, (2) to develop a user-friendly mobile application that offered prescriptions for lifestyle improvement, and (3) to examine whether the developed application had positive effects on users. MATERIALS AND METHODS: In order to develop a lifestyle analysis engine that would operate in an Android(®) (Google, Mountain View, CA)-based mobile application, survey data on health awareness behaviors of 25,124 participants from the 2009 Korean National Health and Nutrition Examination Survey (KNHANES) were analyzed. Additionally, in order for the users to be aware of their lifestyles and explore the effects of the developed mobile application on lifestyle management and improvement, an additional survey of the lifestyle awareness and levels of motivation for lifestyle improvement of 152 users was conducted. RESULTS: The differences between lifestyles before and after using the application were examined. A paired t test was used for questions regarding (1) the level of motivation to improve lifestyles and (2) changes in lifestyle. The lifestyle score was lower after using the program than before using it. Conversely, the level of motivation to improve lifestyle was greater after the program than before it. Both results were statistically significant. CONCLUSIONS: By using the KNHANES, this study developed a mobile application that compared the quantified lifestyles of individuals and enabled individuals to check easily their health statuses, whenever and wherever necessary. The program developed in this study contributed to motivating individuals to be aware of and to improve their lifestyles.
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Promoção da Saúde , Indicadores Básicos de Saúde , Estilo de Vida , Aplicativos Móveis , Inquéritos Epidemiológicos , Humanos , República da CoreiaRESUMO
Aim: To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. Materials & methods: The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 µmol/kg) after intravenous and subcutaneous administration. Results: DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). Conclusion: DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation.
Iron is an essential metal nutrient, but excess iron produces toxic effects that damage multiple organs including the heart, liver and pancreas. Deferoxamine (DFO) is a US FDA-approved drug for treating iron overload, but its use is limited by serious adverse effects and an inconvenient daily dose scheme. The recent development of a DFO-based nanomedicine (DFO-NP) has shown promise in treating iron overload in animals and was safer in animals. Before this new drug can be given to humans, how it is absorbed into the body, processed in the body and removed from the body when given in different amounts and dose routes must be determined. In this study, we tested the absorption, distribution and removal of DFO-NPs after intravenous and subcutaneous injection in rats. This study showed that DFO-NPs behave differently when changing the dose and that subcutaneous injection makes the drug stay in the body longer without ill effect, which means it could be given to patients this way.
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Desferroxamina , Sobrecarga de Ferro , Ratos , Animais , Desferroxamina/farmacocinética , Desferroxamina/uso terapêutico , Quelantes de Ferro/farmacocinética , Quelantes de Ferro/uso terapêutico , Distribuição Tecidual , Ratos Sprague-Dawley , Sobrecarga de Ferro/tratamento farmacológicoRESUMO
Phototheranostics stem from the recent advances in nanomedicines and bioimaging to diagnose and treat human diseases. Since tumors' diversity, heterogeneity, and instability limit the clinical application of traditional diagnostics and therapeutics, phototheranostics, which combine light-induced therapeutic and diagnostic modalities in a single platform, have been widely investigated. Numerous efforts have been made to develop phototheranostics for efficient light-induced antitumor therapeutics with minimal side effects. Herein, we review the fundamentals of phototheranostic nanomedicines with their biomedical applications. Furthermore, the progress of near-infrared fluorescence imaging and cancer treatments, including photodynamic therapy and photothermal therapy, along with chemotherapy, immunotherapy, and gene therapy, are summarized. This review also discusses the opportunities and challenges associated with the clinical translation of phototheranostics in pan-cancer research. Phototheranostics can pave the way for future research, improve the quality of life, and prolong cancer patients' survival times.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Fotoquimioterapia/métodos , Qualidade de Vida , Nanomedicina Teranóstica/métodosRESUMO
The strategy of structure-inherent tumor targeting (SITT) with cyanine-based fluorophores is receiving more attention because no chemical conjugation of targeting moieties is required. However, the targeting mechanism behind SITT has not yet been well explained. Here, it is demonstrated that heptamethine-cyanine-based fluorophores possess not only targetability of tumor microenvironments without the need for additional targeting ligands but also second near-infrared spectral window (NIR-II) imaging capabilities, i.e., minimum scattering and ultralow autofluorescence. The new SITT mechanism suggests that bone-marrow-derived and/or tissue-resident/tumor-associated immune cells can be a principal target for cancer detection due to their abundance in tumoral tissues. Among the tested, SH1 provides ubiquitous tumor targetability and a high tumor-to-background ratio (TBR) ranging from 9.5 to 47 in pancreatic, breast, and lung cancer mouse models upon a single bolus intravenous injection. Furthermore, SH1 can be used to detect small cancerous tissues smaller than 2â¯mm in diameter in orthotopic lung cancer models. Thus, SH1 could be a promising cancer-targeting agent and have a bright future for intraoperative optical imaging and image-guided cancer surgery.
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Neoplasias , Cirurgia Assistida por Computador , Animais , Corantes Fluorescentes , Camundongos , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Cirurgia Assistida por Computador/métodos , Microambiente TumoralRESUMO
Enormous efforts have been made to integrate various therapeutic interventions into multifunctional nanoplatforms, resulting in the advance of nanomedicine. Image-guided drug delivery plays a pivotal role in this field by providing specific targeting as well as image navigation for disease prognosis. Methods: We demonstrate image-guided surgery and drug delivery for the treatment of lung cancer using nanotheranostic H-dots loaded with gefitinib and genistein. Results: The surgical margin for lung tumors is determined by image guidance for precise tumor resection, while targeted anti-cancer drugs function simultaneously for synergistic combination therapy. Compared to conventional chemotherapies, H-dot complexes could improve the therapeutic efficacy of drugs while reducing the risk of adverse effects and drug resistance owing to their ideal biodistribution profiles, high targetability, low nonspecific tissue uptake, and fast renal excretion. Conclusions: These H-dot complexes have unlocked a unique framework for integrating multiple therapeutic and diagnostic modalities into one nanoplatform.
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Antineoplásicos , Neoplasias Pulmonares , Nanopartículas , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Distribuição TecidualRESUMO
Deferoxamine (DFO) is an FDA-approved iron-chelating agent which shows good therapeutic efficacy, however, its short blood half-life presents challenges such as the need for repeated injections or continuous infusions. Considering the lifelong need of chelating agents for iron overload patients, a sustained-release formulation that can reduce the number of chelator administrations is essential. Here, injectable hydrogel formulations prepared by integrating crosslinked hyaluronic acid into Pluronic F127 for an extended release of DFO nanochelators are reported. The subcutaneously injected hydrogel shows a thermosensitive sol-gel transition at physiological body temperature and provides a prolonged release of renal clearable nanochelators over 2 weeks, resulting in a half-life 47-fold longer than that of the nanochelator alone. In addition, no chronic toxicity of the nanochelator-loaded hydrogel is confirmed by biochemical and histological analyses. This injectable hydrogel formulation with DFO nanochelators has the potential to be a promising formulation for the treatment of iron overload disorders.
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Hidrogéis , Sobrecarga de Ferro , Preparações de Ação Retardada/uso terapêutico , Humanos , Ferro , Sobrecarga de Ferro/tratamento farmacológico , Poloxâmero/uso terapêuticoRESUMO
We investigated the association between the severity of diabetic retinopathy (DR) and hearing loss based on vascular etiology. We used data from the Korean National Health and Nutrition Survey 2010-2012. Adults aged >40 years with diabetes were enrolled. Demographic, socioeconomic, general medical, noise exposure and biochemical data were used. Participants were classified into three groups: diabetes without DR, non-proliferative DR (NPDR), and proliferative DR (PDR); participants were also divided into two groups (middle age (40 ≤ age < 65 years) vs. old age (age ≥ 65 years)). The association between hearing loss and DR was determined using logistic regression analysis. A total of 1045 participants (n = 411, middle-aged group; n = 634, old-age group) were enrolled. Overall, the prevalence of hearing loss was 58.1%, 61.4%, and 85.0% in the no DR, NPDR, and PDR groups, respectively. After adjusting for confounding factors, the logistic regression model showed that there was no significant association between the prevalence of DR and hearing loss in the overall sample. However, the presence of PDR (OR 7.74, 95% CI 2.08-28.82) was significantly associated with hearing loss in the middle-aged group. Middle-aged people with diabetes may have an association between DR severity and hearing loss. The potential role of microvascular diseases in the development of hearing loss, especially in middle-aged patients, could be considered.
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In semiconductor industry, low-dielectric-constant SiCOH films are widely used as inter-metal dielectric (IMD) material to reduce a resistance-capacitance delay, which could degrade performances of semiconductor chips. Plasma enhanced chemical vapor deposition (PECVD) system has been employed to fabricate the low-dielectric-constant SiCOH films. In this work, among various parameters (plasma power, deposition pressure, substrate temperature, precursor injection flow rate, etc.), helium carrier gas flow rate was used to modulate the properties of the low-dielectric-constant SiCOH films. Octamethylcyclotetrasiloxane (OMCTS) precursor and helium were injected into the process chamber of PECVD. And then SiCOH films were deposited varying helium carrier gas flow rate. As helium carrier gas flow rate increased from 1500 to 5000 sccm, refractive indices were increased from 1.389 to 1.428 with enhancement of mechanical strength, i.e., increased hardness and elastic modulus from 1.7 and 9.1 GPa to 3.3 and 19.8 GPa, respectively. However, the relative dielectric constant (k) value was slightly increased from 2.72 to 2.97. Through analysis of Fourier transform infrared (FTIR) spectroscopy, the effects of the helium carrier gas flow rate on chemical structure, were investigated. It was thought that the increase in helium carrier gas flow rate could affect the density with changes of chemical structure and composition. In conclusion, regulation of helium carrier gas flow rate can effectively modulate k values and mechanical strength, which is needed for IMD material in semiconductor fabrication possess.
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An injectable, click-crosslinking (Cx) hyaluronic acid (HA) hydrogel scaffold modified with a bone morphogenetic protein-2 (BMP-2) mimetic peptide (BP) was prepared for bone tissue engineering applications. The injectable click-crosslinking HA formulation was prepared from HA-tetrazine (HA-Tet) and HA-cyclooctene (HA-TCO). The Cx-HA hydrogel scaffold was prepared simply by mixing HA-Tet and HA-TCO. The Cx-HA hydrogel scaffold was stable for a longer period than HA both in vitro and in vivo, which was verified via in-vivo fluorescence imaging in real time. BP acted as an osteogenic differentiation factor for human dental pulp stem cells (hDPSCs). After its formation in vivo, the Cx-HA scaffold provided a fine environment for the hDPSCs, and the biocompatibility of the hydrogel scaffold with tissue was good. Like traditional BMP-2, BP induced the osteogenic differentiation of hDPSCs in vitro. The physical properties and injectability of the chemically loaded BP for the Cx-HA hydrogel (Cx-HA-BP) were nearly identical to those of the physically loaded BP hydrogels and the Cx-HA-BP formulation quickly formed a hydrogel scaffold in vivo. The chemically loaded hydrogel scaffold retained the BP for over a month. The Cx-HA-BP hydrogel was better at inducing the osteogenic differentiation of loaded hDPSCs, because it prolonged the availability of BP. In summary, we successfully developed an injectable, click-crosslinking Cx-HA hydrogel scaffold to prolong the availability of BP for efficient bone tissue engineering.
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Hidrogéis , Engenharia Tecidual , Humanos , Ácido Hialurônico , Hidrogéis/farmacologia , Osteogênese , Alicerces TeciduaisRESUMO
To protect unwanted tissue adhesions occurring after surgeries, we aimed to fabricate an anti-adhesive film using cartilage acellular matrix (CAM) with anti-vascular inhibition activity. Additionally, to fabricate anti-adhesive films with tunable swelling, mechanical, and biodegradation properties, a biodegradable polyester (PEP) with N-hydroxysuccinimide (NHS) in the chain end position was synthesized as a cross-linker. CAM/PEP (CP) films were prepared with various CAM: PEP ratios in the wide size with repeatable reproducibility, and then, cross-linked CP (Cx-CP) were obtained by the interpenetrating cross-linking reaction between the amine group on CAM and the NHS group on PEP cross-linkers under thermal treatment. The biodegradation, wettability, swelling, and mechanical properties of the prepared anti-adhesive Cx-CP films were controlled by varying the CAM:PEP ratio. The degradation half-life, contact angle, elastic moduli and toughness of Cx-CP films increased according to the increasing PEP content. Additionally, Cx-CP films significantly inhibits the attachment and proliferation of HUVECs. Cx-CP film prepared by varying the CAM:PEP ratio can be tailored to meet individual requirements for in vivo injured tissues. In animal experiments, anti-adhesive Cx-CP films implanted between the peritoneal wall and the cecum significantly suppressed tissue adhesion between them. Additionally, good adhesion effect observed at anti-adhesive film maintained for proper time period at injured tissues. Taken together, in this work, we successfully achieved strategy for the development of anti-adhesive barrier with tunable swelling, mechanical, and biodegradation properties.
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Adesivos , Cartilagem , Animais , Caproatos , Dioxanos , Estudos de Viabilidade , Lactonas , Reprodutibilidade dos TestesRESUMO
Four organic solar cell (OSC) devices with the bilayer heterojunction architecture were investigated, where carbon nanotubes (CNTs) were doped within the acceptor layer. The power conversion efficiency (PCE) of the CNT-incorporated device with a concentration of 0.004 wt% is approximately 20% point higher than that of the reference one. As the concentration of CNTs became higher, the PCE of the devices deteriorated; this could be caused by the percolative connection of CNTs within the layer. The voltage dependence on the effective lifetime of the charge carriers, determined by Cole-Cole curves of the impedance analysis, was different for the reference and CNT-incorporating devices-the lifetime of the CNT-incorporated ones was shorter, possibly owing to the high local electric field near the CNTs. Controlling the concentration of CNTs below the critical concentration of percolation is a key factor in achieving high photovoltaic performance.