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It is one of the challenges for a wide clinical application of polymer micelles to address the structure disintegration and premature drug release before reaching a pathological site. In the current study, folic acid (FA)-decorated polymer-drug conjugates (FSC) were synthesized with disulfide linkages between camptothecin (CPT) and amphiphilic poly(ethylene glycol)-b-poly(ε-caprolactone) (PECL) copolymers. FSC conjugates were proposed to assemble into micelles with a hydrophobic core of PCL segments and CPT and a hydrophilic corona of PEG segments. The addition of hexadecanol during micelle formation (FSC-16) was proposed to modulate the interactions of hydrophobic segments in micelles and enhance the reductive sensitivity. FSC-16 micelles were obtained with critical micelle concentration of around 2 µg/mL and an average size of around 200 nm, and the conjugated CPT was rapidly released out in response to glutathione. The reductive sensitivity was also demonstrated with respect to the changes of micelle size and morphologies as well as the fluorescent intensity of pyrene loaded in micelles. Benefiting from the FA receptor-mediated uptake and the reduction-sensitive release of CPT, significant cytotoxicity and cell apoptosis were identified for FSC-16 micelles against SKOV-3 cells with strong expressions of FA receptors. Flow cytometry and confocal laser scanning microscopy analyses demonstrated that CPT was distributed into nuclei after cellular uptake and intracellular release from FSC-16 micelles. Thus, the FA-decorated and reduction-sensitive micelles assembled from polymer-drug conjugates show advantages in inhibiting premature release during circulation, enhancing cellular uptake at the tumor tissues, and promoting intracellular release and nuclei location of the active moieties.
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Camptotecina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Lactonas/química , Micelas , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Camptotecina/farmacocinética , Sobrevivência Celular , Relação Dose-Resposta a Droga , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Neoplasias Ovarianas/patologia , Propriedades de Superfície , Distribuição Tecidual , Células Tumorais CultivadasRESUMO
Oral ulcers are a common inflammatory mucosal ulcer, and the moist and dynamic environment in the oral cavity makes topical pharmacological treatment of oral ulcers challenging. Herein, oral ulcer tissue adhesion nanoparticles were prepared by using esterification reaction between polyglutamic acid and tannic acid, and at the same time doxycycline hydrochloride was loaded into the nanoparticles. The obtained slow drug release effect of the drug-loaded nanoparticles reduced the toxicity of the drug, and by penetrating into the fine crevice region of the wound tissue and adhering to it, they could in-situ release the carried drug more effectively and thus have shown significant antibacterial effects. In addition, tannic acid in the system conferred adhesion, antioxidant and immune regulation activities to the nanocarriers. A rat oral ulcer model based on fluorescent labeling was established to investigate the retention of nanoparticles at the ulcer, and the results showed that the retention rate of drug-loaded nanoparticles at the ulcer was 17 times higher than that of pure drug. Due to the antibacterial and immune regulation effects of the drug-loaded nanoparticles, the healing of oral ulcer wounds was greatly accelerated. Such application of doxycycline hydrochloride loaded polyglutamic acid/tannic acid nanoparticles is a novel and effective treatment strategy for oral ulcer.
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Nanopartículas , Úlceras Orais , Ratos , Animais , Úlceras Orais/tratamento farmacológico , Doxiciclina/farmacologia , Úlcera/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas , Ácido Poliglutâmico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , TaninosRESUMO
The application of most hydrogel bio-adhesives is greatly limited due to their high swelling, low underwater adhesion, and single function. Herein, a spatial multi-level physical-chemical and bio-inspired in-situ bonding strategy is proposed, to develop a multifunctional hydrogel bio-glue using polyglutamic acid (PGA), tyramine hydrochloride (TYR), and tannic acid (TA) as precursors and 4-(4,6-dimethoxytriazine-2-yl) -4-methylmorpholine hydrochloride(DMTMM) as condensation agent, which is used for tissue adhesion, hemostasis and repair. By introducing TYR and TA into the PGA chain, it is demonstrated that not only can the strong adhesion of bio-glue to the surface of various fresh tissues and wet materials be realized through the synergistic effect of spatial multi-level physical and chemical bonding, but also this glue can be endowed with the functions of anti-oxidation and hemostasis. The excellent performance of such bio-glue in the repair of the wound, liver, and cartilage is achieved, showing a great potential in clinical application for such bio-glue. This study will open up a brand-new avenue for the development of multifunctional hydrogel biological adhesive.
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Adesivos , Adesivos Teciduais , Humanos , Hidrogéis , Hemostasia , Aderências Teciduais , TaninosRESUMO
The durability of the resin-dentin bonding interface is a key issue in clinical esthetic dentistry. Inspired by the extraordinary bioadhesive properties of marine mussels in a wet environment, we designed and synthetized N-2-(3,4-dihydroxylphenyl) acrylamide (DAA) according to the functional domain of mussel adhesive proteins. DAA's properties of collagen cross-linking, collagenase inhibition, inducing collagen mineralization in vitro, and as a novel prime monomer for clinical dentin adhesion use, its optimal parameters, and effect on the adhesive longevity and the bonding interface's integrity and mineralization, were evaluated in vitro and in vivo. The results showed that oxide DAA can inhibit the activity of collagenase and cross collagen fibers to improve the anti-enzymatic hydrolysis of collagen fibers and induce intrafibrillar and interfibrillar collagen mineralization. As a primer used in the etch-rinse tooth adhesive system, oxide DAA can improve the durability and integrity of the bonding interface by anti-degradation and mineralization of the exposed collagen matrix. Oxidized DAA (OX-DAA) is a promising primer for improving dentin durability; using 5% OX-DAA ethanol solution and treating the etched dentin surface for 30 s is the optimal choice when used as a primer in the etch-rinse tooth adhesive system.
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PURPOSE: Biodegradable polymers containing acid-labile segments and galactose grafts were formulated into nanoparticles in current study, and enhanced cellular uptake and subcellular distribution were clarified. METHODS: Quantum dots (QDs) was utilized as an imaging agent and a model of bioactive substances, and entrapped into nanoparticles of around 200 nm through a nanoprecipitation process. RESULTS: The acid-labile characteristics of QDs-loaded nanoparticles were approved by the hemolysis capability, the degradation behaviors of matrix polymers, and the fluorescence decay of entrapped QDs after incubation into buffer solutions of different pH values. The galactose grafts increased the acid-lability, due to the hydrophilic moieties on the acid-labile segments, and enhanced uptake efficiency of over 50 % was found after 4 h incubation with HepG2 cells, due to the galactose-receptor mediated endocytosis. The acid-lability led to an efficient endosomal escape of QDs-loaded nanoparticles into cytoplasm. CONCLUSIONS: The integration of acid-lability, targeting effect, and full biodegradable backbone into nanoparticle matrices constitutes a promising platform for intracellular delivery of bioactive substances for disease diagnosis, imaging and treatment.
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Galactose/química , Nanopartículas/análise , Pontos Quânticos , Ácidos/química , Linhagem Celular Tumoral , Endocitose , Eritrócitos/citologia , Galactose/metabolismo , Hemólise , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas/química , Nanopartículas/ultraestruturaRESUMO
Magnesium and its alloys have been widely studied as absorbable coronary stent materials. However, the rapid corrosion rate in the intravascular environment inhibits the application of magnesium-based stents. In order to endow magnesium-based stent with appropriate degradation rate and biocompatibility, a hydrophobic layer was constructed by in situ cyclic grafting 4,4'-diphenylmethane diisocyanate and aminopropyl-terminated polydimethylsiloxane on pure magnesium. SEM-EDS, X-ray photoelectron spectroscopy and water contact angle were detected to analyze the chemical composition of the layer. The amino groups were confirmed to be introduced on the surface which provide a platform for subsequent modification. The contact angle value of the modified surface is 132.1°, indicating a hydrophilic surface. The electrochemical measurements and immersion tests demonstrated that the hydrophobic layer significantly improved the anti-corrosion ability of the substrate. Besides, the biocompatibility of the hydrophobic surface was examined by platelet adhesion, cytocompatibility in vitro and subcutaneous implantation in vivo. Immunological and histological results indicated that the hydrophobic layer had excellent biocompatibility. Therefore, the presented study might be a promising method for the surface modification of biomedical magnesium-based stent.
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In this study, a sulfur-mediated polycarbonate polyurethane (PCU-SS) is developed by mimicking the catalyzing ability of glutathione peroxidase (GPx) on nitric oxide (NO) in the human body. The PCU-SS is endowed with the capability to produce NO based on disulfide bonds, which could strongly improve the biocompatibility of the materials. The characterization results indicate that PCU-SS could not only decrease the adhesion of platelets but also enhance the capability of anti-thrombus. Moreover, it is shown that PCU-SS has a good compatibility with endothelial cells (ECs), while has a marked inhibition capacity of the proliferation of smooth muscle cells (SMCs) and macrophages (MA). Meanwhile, the result of animal implantation experiments further demonstrates the good abilities of PCU-SS on anti-inflammation, anti-thrombus, and anti-hyperplasia. Our results offer a novel strategy for the modification of blood-contacting materials based on disulfide bonds. It is expected that the PCU-SS could shed new light on biocompatibility improvement of cardiovascular stents.
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Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.
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Many polyurethanes (PUs) are blood-contacting materials due to their good mechanical properties, fatigue resistance, cytocompatibility, biosafety, and relatively good hemocompatibility. Further functionalization of the PUs using chemical synthetic methods is especially attractive for expanding their applications. Herein, a series of catechol functionalized PU (C-PU-PTMEG) elastomers containing variable molecular weight of polytetramethylene ether glycol (PTMEG) soft segment are reported by stepwise polymerization and further introduction of catechol. Tailoring the molecular weight of PTMEG fragment enables a regulable catechol content, mobility of the chain segment, hydrogen bond and microphase separation of the C-PU-PTMEG elastomers, thus offering tunability of mechanical strength (such as breaking strength from 1.3 MPa to 5.7 MPa), adhesion, self-healing efficiency (from 14.9% to 96.7% within 2 hours), anticoagulant, antioxidation, anti-inflammatory properties and cellular growth behavior. As cardiovascular stent coatings, the C-PU-PTMEGs demonstrate enough flexibility to withstand deformation during the balloon dilation procedure. Of special importance is that the C-PU-PTMEG-coated surfaces show the ability to rapidly scavenge free radicals to maintain normal growth of endothelial cells, inhibit smooth muscle cell proliferation, mediate inflammatory response, and reduce thrombus formation. With the universality of surface adhesion and tunable multifunctionality, these novel C-PU-PTMEG elastomers should find potential usage in artificial heart valves and surface engineering of stents.
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Stent implantation is the primary method used to treat coronary heart disease. However, it is associated with complications such as restenosis and late thrombosis. Despite surface modification being an effective way to improve the biocompatibility of stents, the current research studies are not focused on changes in the vascular microenvironment at the implantation site. In the present study, an adaptive drug-loaded coating was constructed on the surface of vascular stent materials that can respond to oxidative stress at the site of vascular lesions. Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium. EGCG has antioxidant activity, and pitavastatin calcium can inhibit smooth muscle cell proliferation. Therefore, EGCG and pitavastatin calcium provided a synergistic anti-inflammatory effect. Moreover, the coating was cross-linked using disulfide bonds, which accelerated the release of the drug in response to reactive oxygen species. A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo.
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Stents Farmacológicos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Animais , Catequina/administração & dosagem , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Reestenose Coronária/prevenção & controle , Cistamina/administração & dosagem , Cistamina/química , Liberação Controlada de Fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Quinolinas/administração & dosagem , Quinolinas/química , Quinolinas/farmacologia , Coelhos , Ratos Sprague-Dawley , Aço Inoxidável/químicaRESUMO
The reconstruction of the intra/interfibrillar mineralized collagen microstructure is extremely important in biomaterial science and regeneration medicine. However, certain problems, such as low efficiency and long period of mineralization, are apparent, and the mechanism of interfibrillar mineralization is often neglected in the present literature. Thus, we propose a novel model of biomimetic collagen mineralization that uses molecules with the dual function of cross-linking collagen and regulating collagen mineralization to construct the intrafibrillar and interfibrillar collagen mineralization of the structure of mineralized collagen hard tissues. In the present study completed in vitro, N-2-(3,4-dihydroxyphenyl) acrylamide (DAA) is used to bind and cross-link collagen molecules and further stabilize the self-assembled collagen fibers. The DAA-collagen complex provides more affinity with calcium and phosphate ions, which can reduce the calcium phosphate/collagen interfacial energy to promote hydroxyapatite (HA) nucleation and accelerate the rate of collagen fiber mineralization. Besides inducing intrafibrillar mineralization, the DAA-collagen complex mineralization template can realize interfibrillar mineralization with the c-axis of the HA crystal on the surface of collagen fibers and between fibers that are parallel to the long axis of collagen fibers. The DAA-collagen complex, as a new type of mineralization template, may provide a new collagen mineralization strategy to produce a mineralized scaffold material for tissue engineering or develop bone-like materials.
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Acrilamida/química , Materiais Biomiméticos/química , Colágeno/química , Dopamina/química , Osso e Ossos , Cálcio/química , Cálcio/metabolismo , Fosfatos de Cálcio/química , Reagentes de Ligações Cruzadas/química , Cristalização , Durapatita/química , Durapatita/metabolismo , Matriz Extracelular/metabolismo , Humanos , Simulação de Dinâmica Molecular , Polimerização , Medicina Regenerativa , Propriedades de Superfície , Engenharia TecidualRESUMO
As an important class of biomaterialsï¼bionics inspired materials has been widely used in creating extracorporeal and implantable medical devices. However, specific service environment is often faced with multiple requirements rather than single function. Herein, we designed a phospholipid-based multifunctional coating with phospholipids-based polymers, type I collagen (Col-I) and Arg-Glu-Asp-Val (REDV) peptide, via layer-by-layer assembly. The successful synthesis of the polymers and the coating is proved by a series of characterization methods including Fourier transforming infrared spectra (FTIR), proton nuclear magnetic resonance (1H NMR), ultraviolet-visible spectra (UV) and X-ray photoelectron spectroscopy (XPS), while the assembly process and quality change of the coating were monitored via quartz crystal microbalance (QCM). Besides, hydrophilicity and roughness of this coating was analyzed via water contact angle (WCA) and atomic force microscope (AFM), respectively. Finally, results from platelet adhesion, activation assay, smooth muscle cells (SMCs) and endothelial cells (ECs) cultures indicated that the multifunctional coating could strongly inhibit platelet adhesion and SMCs proliferation, hence provide practical application of the coating with good biocompatibility, especially the anticoagulant property and cell compatibility. It is expected that this coating may be used in blood-contacting fields such as cardiovascular stent or other devices in the future.
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Células Endoteliais , Fosfolipídeos , Materiais Biocompatíveis , Adesividade Plaquetária , Propriedades de SuperfícieRESUMO
Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress-strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.
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This study is aimed to investigate the relationship of the mechanism and the effect of polyphenol derivatives cross-linking collagen with polyphenol molecular structural complexity and reaction conditions of polyphenols with collagen and to present a reference for cross-linker selection. Three kinds of polyphenols were selected to cross-link collagen under nonoxidized and oxidized conditions in vitro. These polyphenols included tannic acid, which represents the most complex stereo structure and the highest number of phenolic hydroxyl groups; epigallocatechin gallate, which represents a moderately complex structure and contains fewer phenolic hydroxyl groups than tannic acid; and N-2-(3,4-dihydroxylphenyl) ethyl acrylamide, which represents only one hydroxyl phenol group. Particle size analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, attenuated total reflection Fourier transform infrared spectroscopy, and cross-linking degree analysis were conducted. Mechanical properties, thermal stability, swelling properties, hydrophilicity, and antienzymolysis properties were also determined. Results showed that all polyphenol derivatives cross-linked collagen mainly by noncovalent bonding under acidic nonoxidized conditions and by covalent bonding under alkaline-oxidized conditions. In general, the modification effect of polyphenol on collagen was related to its molecular complexity and the number of its phenolic hydroxyls. Several phenolic hydroxyls in the polyphenol derivative caused a good modification effect on collagen, especially under acidic nonoxidized conditions. Under alkaline conditions, each polyphenol was oxidized, resulting in improved cross-linking strength by covalent bonding compared to that under acidic nonoxidized condition via noncovalent bonding. The selection of cross-linkers and cross-linking conditions should be based on the purpose of collagen modification consistent with the effect of cross-linking.
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To regulate the behaviors and functions of endothelial cells (ECs) on the biomaterials on titanium (Ti), a biomimetic micropattern (ridge/groove: 25/25 µm) of polymer of 2-methacryloyloxyethyl phosphorylcholine (polyMPC) and Gly-Arg-Glu-Asp-Val-Tyr (GREDVY) was fabricated. PMMPC (monomer contain MPC and methacrylic acid (MA)) containing carboxyl groups was chosen, and PMMPC was cross-linked with hexamethylene diamine through condensation reaction of amino and carboxyl. Simultaneously, the carboxyl groups of cross-linked PMMPC (PMMPC-HD) can react with amino groups of polydopamine which can adhered on many materials firmly. GREDVY was immobilized on polydopamine but not on PMMPC-HD because amino and carboxyl groups can react with catechol and amino groups of polydopamine. IR and 1H NMR demonstrated that PMMPC-HD was successfully synthesized. And the QCM-D (quartz crystal microbalance with dissipation) and IR approved that PMMPC-HD and GREDVY can be immobilized on polydopamine (PDA). Platelet adhesion and whole blood adhesion on micropattern modificated with PMMPC and GREDVY (Ti-PDA-M/R(P)) showed better hemocompatibility than other samples. Endothelial cells were regulated in the direction of micropattern showing elongated ECs were closer to a healthy, athero-protective phenotype than ECs cultured in vitro without micropattern. NO and PGI2 release were upregulated. Simultaneously the number of SMCs on Ti-PDA-M/R(P) was the smaller that of other samples, which demonstrated that the Ti-PDA-M/R(P) had property of inhibiting SMCs proliferation to a certain extent.
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Abstracts Here we report the anticoagulant property of Sulfonated Silk Fibroin (SSF) which was improved by sulfonation method. Chlorosulfonic acid was applied to modify the Silk Fibroin (SF) anticoagulant property by the preparation of the SSF. The SSF was prepared in the new technology that 50 °C, 0.2 g SF/ml chlorosulfonic acid and 15 h were optimized with the reaction temperature, special concentration ratio of the SF to the chlorosulfonic acid and the certain reaction time, respectively. Then the SF reaction solution was dialyzed, and freeze-dried to form the SSF. The different properties of the SF and the SSF have been revealed by Fourier Transform Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Photoelectron Spectrometer (XPS), Gel Permeation Chromatography (GPC), X-ray Diffraction (XRD), Activated Partial Thromboplastin Time (APTT) etc. That the sulfonic acid groups were successfully induced into the SF molecular chains has also been verified. The SSF possessed the excellent performance on the APTT value, and it can be slowly released from the Poly(epsilon-caprolactone) (PCL) composite film. In conclusion, the SSF is the novel product modified by the chlorosulfonic acid directly, and it possesses the good anti-coagulation, resulting in that it can become one of candidates of anti-coagulation materials.
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Anticoagulantes/química , Portadores de Fármacos/química , Fibroínas/química , Poliésteres/química , Ácidos Sulfônicos/química , Alicerces Teciduais/química , Anticoagulantes/administração & dosagem , Materiais Biocompatíveis/química , Tempo de Tromboplastina Parcial , Propriedades de SuperfícieRESUMO
Reversible networks are a key factor for designing self-healing hydrogels with high stretching properties. To achieve that, it is often necessary to modify or graft functional groups to the main chains for inducing the formation of reversible covalent-bond-based chemical cross-linking or hydrogen-bond-based physical cross-linking, thus leading to a complicated chemical process and high cost. Here, we proposed a dynamic sliding physical crosslinking mechanism of chains to design and synthesize hydrogels with both good self-healing ability and extensibility by introducing interstitial phases of small organic molecules into the hydrogel networks to enhance hydrogen bonds, which has been proved to be a quite facile and practical approach to achieve stretchable and self-healing properties. Our work might greatly promote our ability to understand the role of hydrogen bonds that are often overlooked in the design of materials. The as-synthesized hydrogels displayed extraordinary swelling properties with a swelling ratio of 2750% in PBS and of nearly 10 000% in stilled water, respectively, and they also showed excellent performance after many stress cycles under 95% compressive deformation. The use of 10% diethylene glycol could allow the elongation to be increased from 238% to 2705%. Our cell and animal experimental studies indicated that the as-synthesized supramolecular hydrogels have good biocompatibility and bioactivity and show potential for clinical application.
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Surface biofunctional modification of cardiovascular implants via the conjugation of biomolecules to prevent thrombosis and restenosis formation and to accelerate endothelialization has attracted considerable research interest. In this study, we aimed to develop a multifunctional surface that could exhibit good hemocompatibility and function well in inducing desirable vascular cell-material interactions. The multifunctional coating (PCDLOPTPT@Ti), containing phosphorylcholine groups and endothelial progenitor cell (EPC)-specific peptides (PT), was prepared on titanium (Ti) surfaces via chemical conjugation. The results of platelet adhesion, activation, fibrinogen denaturation, and whole blood dynamic adhesion testing indicated that the PCDLOPTPT@Ti coating presented a better hemocompatibility when compared with bare Ti and other control samples. In vitro EPC and smooth muscle cell (SMC) cultures showed that the PCDLOPTPT@Ti coating significantly promoted the adhesion and proliferation of EPCs and inhibited the attachment and proliferation of SMCs. In vivo animal tests further confirmed that the PCDLOPTPT@Ti coating effectively inhibited thrombus formation and intimal hyperplasia while supporting endothelium regeneration. These results effectively suggest that the PCDLOPTPT@Ti coating may be promising as a coating on cardiovascular implants.
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Magnesium as well as its alloys appears increasingly as a revolutionary bio-metal for biodegradable implants application but the biggest challenges exist in its too fast bio-corrosion/degradation. Both corrosion-controllable and bio-compatible Mg-based bio-metal is highly desirable in clinic. In present work, hexamethylenediaminetetrakis (methylenephosphonic acid) [HDTMPA, (H2 O3 P-CH2 )2 -N-(CH2 )6 -N-(CH2 -PO3 H2 )2 ], as a natural and bioactive organic substance, was covalently immobilized and chelating-deposited onto Mg surface by means of chemical conversion process and dip-coating method, to fullfill dual-task performance of corrosion-protective and osteo-compatible functionalities. The chemical grafting of HDTMPA molecules, by participation of functional groups on pretreated Mg surface, ensured a firmly anchored base layer, and then sub-sequential chelating reactions of HDTMPA molecules guaranteed a homogenous and dense HDTMPA coating deposition on Mg substrate. Electrochemical corrosion and immersion degradation results reveal that the HDTMPA coated Mg provides a significantly better controlled bio-corrosion/degradation behavior in phosphate buffer saline solution as compared with untreated Mg from perspective of clinic requirement. Moreover, the HDTMPA coated Mg exhibits osteo-compatible in that it induces not only bioactivity of bone-like apatite precipitation but also promotes osteoblast cells adhesion and proliferation. Our well-controlled biodegradable and biocompatible HDTMPA modified Mg might bode well for next generation bone implant application.