Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Nanomedicine ; 35: 102398, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33901646

RESUMEN

Bacterial membrane vesicles (MVs) are particles secreted by bacteria with diameter of 20-400 nm. The pathogen-associated molecular patterns (PAMPs) present on the surface of MVs are capable of activating human immune system, leading to non-specific immune response and specific immune response. Due to the immunostimulatory properties and proteoliposome nanostructures, MVs have been increasingly explored as vaccines or delivery systems for the prevention and treatment of bacterial infections. Herein, the recent progresses of MVs for antibacterial applications are reviewed to provide an overview of MVs vaccines and MVs-related delivery systems. In addition, the safety issues of bacterial MVs are discussed to demonstrate their potential for clinical translation. In the end of this review, the challenges of bacterial MVs as vaccines and delivery systems for clinical applications are highlighted with the purpose of predicting future research directions in this field.


Asunto(s)
Bacterias , Infecciones Bacterianas , Proteínas Bacterianas , Vacunas Bacterianas , Membrana Celular , Nanoestructuras , Bacterias/química , Bacterias/inmunología , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/prevención & control , Proteínas Bacterianas/química , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/uso terapéutico , Vacunas Bacterianas/química , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/uso terapéutico , Membrana Celular/química , Membrana Celular/inmunología , Humanos , Liposomas , Nanoestructuras/química , Nanoestructuras/uso terapéutico
2.
Biomacromolecules ; 16(7): 1967-77, 2015 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-26039032

RESUMEN

Microbial colonization and biofilm formation is the leading cause of contact lens-related keratitis. Treatment of the condition remains a challenge because of the need for prolonged therapeutic course and high doses of antimicrobial agents especially for biofilm eradication. The development of strategies to prepare nonfouling contact lens surfaces is a more practical way to ensure users' safety and relieve the excessive public healthcare burden. In this study, we report a series of polymers that were modified to introduce functionality designed to facilitate coating adhesion, antimicrobial and antifouling properties. Cyclic carbonate monomers having different functional groups including adhesive catechol, antifouling poly(ethylene glycol) (PEG), and hydrophobic urea/ethyl were conjugated onto branched poly(ethylenimine) (bPEI, 25 kDa) at various degrees in a facile and well-controlled manner using a simple one step, atom economical approach. Immersion of contact lenses into an aqueous solution of the catechol-functionalized polymers at room temperature resulted in robust and stable coating on the lens surfaces, which survived the harsh condition of autoclaving and remained on the surface for a typical device application lifetime (7 days). The deposition of the polymer was unambiguously confirmed by static contact angle measurement and X-ray photoelectron spectroscopy (XPS). Polymer coating did not change light transmission significantly. Combinatorial optimization demonstrated that lenses coated with bPEI functionalized with catechol, PEG (5 kDa) and urea groups at 1:12:3:23 molar ratio for 18 h provided the highest antifouling effect against four types of keratitis-causing pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Fusarium solani, after 7 days of incubation. The polymer coating also inhibited protein adsorption onto the contact lens surfaces after exposure to bovine serum albumin solution for up to 24 h, owing to the flexible and large PEG constituent. Notably, all the polymer coatings used in this study were biocompatible, achieving ≥90% cell viability following direct contact with human corneal epithelial cells for 24 h. Hence, these polymer coatings are envisaged to be promising for the prevention of contact lens-related keratitis.


Asunto(s)
Antibacterianos/síntesis química , Aziridinas/química , Materiales Biocompatibles Revestidos/síntesis química , Lentes de Contacto/microbiología , Queratitis/prevención & control , Adsorción/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Línea Celular , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Humanos , Queratitis/tratamiento farmacológico , Queratitis/etiología , Queratitis/microbiología , Ensayo de Materiales , Polietilenglicoles/química
3.
Adv Healthc Mater ; 13(10): e2303454, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38031989

RESUMEN

Neuroinflammation is associated with a series of pathological symptoms in Parkinson's disease (PD), including α-synuclein aggregation and dopaminergic neuronal death. The NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation at the lesion site and is a promising target for PD treatment. In this study, a nanoscale metal-organic framework (Zr-FeP MOF) based nanozyme is fabricated using Fe-5,10,15,20-tetra (4-carboxyphenyl) porphyrin (Fe-TCPP) and Zr6 cluster as ligands. The Zr-FeP MOF is subsequently encapsulated with mannitol (Man)-liposome, resulting in the formation of Zr-FeP MOF@Man liposome (MOF@Man Liposome) nanozyme system. The in vitro studies show that this nanozyme system is effective in relieving the formation of NLRP3 inflammasome and mitochondrial dysfunction. In mouse models of PD, the nanozyme system demonstrates a significant blood-brain barrier-crossing capability attributed to the Man-mediated brain targeting. Additionally, transcriptomic and biochemical studies show that the nanozyme system effectively inhibits the formation and assembly of inflammasome components, mitigating the activation of glial cells and neuroinflammatory response, and ultimately regulating the pathological symptoms of PD effectively.


Asunto(s)
Estructuras Metalorgánicas , Enfermedad de Parkinson , Humanos , Ratones , Animales , Inflamasomas/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR/metabolismo , Enfermedades Neuroinflamatorias , Liposomas , Microglía , Ratones Endogámicos C57BL
4.
Sci Adv ; 10(14): eadk9754, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578994

RESUMEN

The lack of bacterial-targeting function in antibiotics and their prophylactic usage have caused overuse of antibiotics, which lead to antibiotic resistance and inevitable long-term toxicity. To overcome these issues, we develop neutrophil-bacterial hybrid cell membrane vesicle (HMV)-coated biofunctional lipid nanoparticles (LNP@HMVs), which are designed to transport antibiotics specifically to bacterial cells at the infection site for the effective treatment and prophylaxis of bacterial infection. The dual targeting ability of HMVs to inflammatory vascular endothelial cells and homologous Gram-negative bacterial cells results in targeted accumulation of LNP@HMVs in the site of infections. LNP@HMVs loaded with the antibiotic norfloxacin not only exhibit enhanced activity against planktonic bacteria and bacterial biofilms in vitro but also achieve potent therapeutic efficacy in treating both systemic infection and lung infection. Furthermore, LNP@HMVs trigger the activation of specific humoral and cellular immunity to prevent bacterial infection. Together, LNP@HMVs provide a promising strategy to effectively treat and prevent bacterial infection.


Asunto(s)
Infecciones Bacterianas , Nanopartículas , Humanos , Células Endoteliales , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Liposomas
5.
Biomaterials ; 309: 122573, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38677222

RESUMEN

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Micelas , Nanopartículas , Edición Génica/métodos , Nanopartículas/química , Sistemas CRISPR-Cas/genética , Animales , Humanos , Neoplasias/terapia , Neoplasias/genética , Ratones Desnudos , Ratones , Polietilenglicoles/química , Línea Celular Tumoral , Ratones Endogámicos BALB C , Polímeros/química
6.
J Mater Sci Mater Med ; 24(11): 2577-87, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23851928

RESUMEN

The potential of cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs) on emulsion electrospun scaffold containing poly(L-lactic acid)-co-poly-(ε-caprolactone), gelatin and vascular endothelial growth factor (PLCL/GV) was investigated in this study. The characterizations of the scaffold were carried out using scanning electron microscope (SEM), transmission electron microscope, water contact angle and porometer. The proliferation of hMSCs showed that 73.4% higher cell proliferation on PLCL/GV scaffolds than that on PLCL scaffold after 20 days of cell culture. Results of 5-chloromethylfluorescein diacetate staining and SEM morphology analysis indicated that hMSCs differentiated on PLCL/GV scaffolds showed irregular morphology of cardiomyocyte phenotype compared to the typical long and thin hMSC phenotype. Immunostaining results showed the expression of alpha actinin and myosin heavy chain. Our studies identified emulsion electrospinning as a method for fabrication of core-shell fibers suitable for the differentiation of stem cells to cardiac cells, with potential application in cardiac regeneration.


Asunto(s)
Diferenciación Celular , Emulsiones , Gelatina , Células Madre Mesenquimatosas/citología , Miocitos Cardíacos/citología , Nanofibras , Poliésteres , Andamios del Tejido , Materiales Biocompatibles , Proliferación Celular , Células Cultivadas , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión
7.
Adv Healthc Mater ; 12(24): e2202903, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37523195

RESUMEN

Antibiotic colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin-resistant bacteria via a checkerboard assay. For the co-delivery of curcumin and colistin, negatively charged poly(ethylene glycol)-functionalized liposomes encapsulating both drugs (Lipo-cc) are prepared. Killing kinetics and live/dead assays confirm the antibacterial activity of Lipo-cc against colistin-resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo-cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo-cc does not exhibit any toxicity. The therapeutic efficacy of Lipo-cc is further demonstrated in an intestinal bacterial infection model induced with colistin-resistant Escherichia coli. Lipo-cc reduces the bacterial burden with over 6-log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo-cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo-cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin-resistant bacterial infections.


Asunto(s)
Curcumina , Infecciones por Bacterias Gramnegativas , Humanos , Colistina/farmacología , Colistina/uso terapéutico , Curcumina/farmacología , Curcumina/uso terapéutico , Liposomas/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Escherichia coli , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana
8.
ACS Nano ; 17(16): 15411-15423, 2023 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-37534992

RESUMEN

Colistin is the last-resort antibiotic to treat multidrug-resistant (MDR) Gram-negative bacterial infections that are untreatable by other clinically available antibiotics. However, the recently merged plasmid-borne gene mobilized colistin resistance (mcr) leads to modification of the colistin target (i.e., bacterial membrane), greatly compromising the therapy outcome of colistin. To address this unmet clinical need, a nanocomplex (CMS-pEt_20 NP) of anionic prodrug colistin methanesulfonate (CMS) and guanidinium-functionalized cationic polymer pEt_20 is developed through facile self-assembly for co-delivering an antibiotic and antimicrobial polymer with membrane affinity to reverse colistin resistance. The CMS-pEt_20 NP formation enables reversal of colistin resistance and complete killing of clinically isolated mcr-positive colistin-resistant bacteria including MDR E. coli and K. pneumoniae, while monotreatment of polymer or antibiotic at equivalent doses exhibits no antibacterial activity. Mechanistic studies reveal that the CMS-pEt_20 NP enhanced the affinity of delivered CMS to the modified membrane of colistin-resistant bacteria, reviving the membrane lytic property of colistin. The increased membrane permeability caused by colistin in turn promotes an influx of pEt_20 to generate intracellular ROS stress, resulting in elimination of colistin-resistant bacteria. More importantly, a colistin-resistant mouse peritonitis-sepsis infection model demonstrates the excellent therapeutic efficacy of CMS-pEt_20 NP with 100% survival of the infected mouse. In addition, the nanocomplex is proven not toxic both in vitro and in vivo. Taken together, the self-assembled antibiotic-polymer nanocomplex with two complementary antibacterial mechanisms successfully reverses the colistin resistance phenotype in bacteria, and it can be a potential strategy to treat untreatable colistin-resistant MDR bacterial infections.


Asunto(s)
Antibacterianos , Colistina , Animales , Ratones , Antibacterianos/farmacología , Colistina/farmacología , Escherichia coli , Polímeros , Farmacorresistencia Bacteriana , Klebsiella pneumoniae , Fenotipo , Pruebas de Sensibilidad Microbiana
9.
Bioresour Technol ; 352: 127100, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35367606

RESUMEN

Hydrothermal liquefaction (HTL) of starch, cellulose, pectin, and chitin with Pd/C, Co-Mo/γ-Al2O3, and zeolite was investigated at 320 °C for 30 min. Using Co-Mo/γ-Al2O3 at 5 wt% loading led to the highest biocrude yields from starch (25 wt%) and cellulose (23 wt%). The yields from cellulose are more than twice those from noncatalytic HTL (11 wt%). Co-Mo/γ-Al2O3 was also the only catalyst (25 wt% loading) to increase biocrude yields (by 1.6 - 2.6 wt%) from HTL of chitin and pectin. The biocrudes were characterized by elemental analysis, TGA, FT-IR and GC-MS. Catalytic HTL with Co-Mo/γ-Al2O3 had little effect on the elemental composition of the biocrudes. The presence of Co-Mo/γ-Al2O3 increased the low-boiling portion of biocrude from<30% to over 50% for HTL of starch. Finally, a component additivity model that accurately predicts biocrude yields from catalytic HTL of a mixture is presented.


Asunto(s)
Polisacáridos , Almidón , Biocombustibles/análisis , Biomasa , Celulosa , Quitina , Pectinas , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Agua
10.
Adv Healthc Mater ; 11(15): e2200902, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35608275

RESUMEN

Antibacterial hydrogels, particularly antibiotic-loaded hydrogels, are promising wound dressing materials for treatment of bacteria-infected wound. However, it is challenging to achieve sustained release of antibiotics from hydrogels through physical encapsulation of the antibiotics. Herein, an interpenetrating polymer network P(AA-co-HEMA)Gen hydrogel is reported with double crosslinking formed by free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA), while using the antibiotic gentamicin (Gen) as the dynamic physical crosslinker. Gentamicin is incorporated into the hydrogel networks via electrostatic interaction between the carboxyl groups of poly(acrylic acid) and the amino groups of gentamicin, which leads to pH-responsive drug release and a significant increase in mechanical strength (i.e., elastic modulus, viscous modulus, and compressive modulus). More importantly, the hydrogels with optimal compositions demonstrate long-lasting antibacterial activity against both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) over 28 d. The in vivo studies that are conducted in an S. aureus-infected full-thickness skin wound model demonstrate that the double crosslinking hydrogels loaded with gentamicin eliminate bacteria in the wounds more effectively and significantly accelerate wound healing as compared to 3M dressing and the control without any treatment. Taken together, this antibiotic-loaded interpenetrating polymer network hydrogel is potentially a promising wound dressing material for the treatment of bacteria-infected wound.


Asunto(s)
Hidrogeles , Infección de Heridas , Antibacterianos/farmacología , Escherichia coli , Gentamicinas/farmacología , Humanos , Hidrogeles/farmacología , Polímeros/farmacología , Staphylococcus aureus
11.
Biomater Adv ; 133: 112644, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35525743

RESUMEN

The titanium implant surface topography optimization for improving osseointegration has been performed for many years, whereas understanding the mechanisms of topography-induced osteogenic differentiation is still insufficient. In this study, the micro/nano-textured topography was created on titanium implant surface by acid etching and anodization. The MC3T3-E1 cells were incubated with different surfaces and the RNA sequencing technique was performed to obtain the transcriptomic information, which suggested the enrichment at "membrane" and "organelle" (GO) as well as "Calcium signal pathway" (KEGG). Consequently, a special attention was paid to the store-operated calcium entry (SOCE) mediated by Orai1 at ER-PM contact site. By fluorescence staining and western blot, it was confirmed that the Orai1 was upregulated on the micro/nano-textured titanium surface, which was correlated to the enhanced osteogenic differentiation induced by topography. Further experiments indicated that the CaMKII/ERK1/2 pathway was involved in. This research is the first time giving a comprehensive transcriptomic information of osteoblasts on micro/nano-textured topography and may provide deeper insight into the interaction between biomaterials and host.


Asunto(s)
Osteogénesis , Titanio , Materiales Biocompatibles , Diferenciación Celular/genética , Osteoblastos , Osteogénesis/genética , Titanio/farmacología
12.
Adv Healthc Mater ; 11(19): e2200960, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35833876

RESUMEN

The major challenges of photothermal therapy (PTT) toward clinical application are the severe skin injury and inflammation response associated with high power laser irradiation. Herein, polydopamine nanoparticles (PDA-EST and PDA-RAL) targeted to estrogen receptor α (ERα) for efficient ablation of breast tumor under a low irradiation density of 0.1 W cm-2 are reported. These nanoparticles are capable of recruiting ERα on their surface and induce a complete ERα degradation via localized heat. Owing to the ERα targetability, PDA-EST and PDA-RAL strongly suppress the proliferation of breast cancer cells without causing significant inflammation. This work provides a generalized method for enhancing PTT efficacy under low irradiation density.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Receptor alfa de Estrógeno , Femenino , Humanos , Indoles , Inflamación , Fototerapia , Polímeros
13.
J Control Release ; 329: 871-881, 2021 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-33058933

RESUMEN

Despite the good clinical outcomes of total joint replacements, prosthetic joint infections still remain a significant cause of implant failure. Primary prophylaxis is key to stemming this burgeoning problem and its associated complications. In this study, a series of bone cement formulations with enhanced antibacterial performance have been developed through the addition of carboxylic acid-functionalized polycarbonate block copolymers to commercially available bone cement. Block copolymer design features were specifically tailored to modulate the acidity for adsorption of antibiotic and phase separation of the copolymers within the polymerizing/hardening of the cement during application. The best performing polymers demonstrated sustained antimicrobial release for more than 259 days and 147 days against S. aureus and P. aeruginosa, respectively, compared to 70 days of activity seen with commercially available gentamicin-containing cement control; whilst in vitro gentamicin release was increased by 8-fold. Total porosity was also increased 3-fold from 4.3% to 12.5%, whilst maintaining the mechanical integrity, working characteristics and osteoblastic biocompatibility of bone cement. Taken together, carboxylic acid-functionalized polycarbonates represent a promising class of bone cement additives that can be used to enhance the antibacterial performance of the bone cement whilst maintaining mechanical strength and cellular biocompatibility.


Asunto(s)
Antibacterianos , Cementos para Huesos , Ácidos Carboxílicos , Preparaciones de Acción Retardada , Gentamicinas , Cemento de Policarboxilato , Polimetil Metacrilato , Staphylococcus aureus
14.
J Mech Behav Biomed Mater ; 98: 48-57, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31195187

RESUMEN

Coaxial electrospinning, in which Poly (L-lactic acid-co-ε-caprolactone) (PLC) with different Lactic acid (LA) to caprolactone (CL) ratio (75:25 and 50:50) were employed to electrospin core-shell nanofibers which could mimic the native extracellular matrix for tissue engineering applications. Core-shell nanofibrous scaffolds of PLC (50:50)/BSA (426 ±â€¯157 nm) and PLC (75:25)/BSA (427 ±â€¯197 nm) were fabricated and model drug bovine serum albumin (BSA) was entrapped in the core layer. The morphology, core-shell structure and sustained release behaviors were evaluated by Scanning electron microscopy (SEM), transmission electron microscopy (TEM), inverted fluorescence microscopy, water contact angle test and in vitro release test, respectively. The effect of core-shell structure and shell layer materials on the variation tendency of mechanical characterization in dry and wet situation were also investigated by tensile testing. The in vitro biocompatibility of scaffolds were investigated by growing human mesenchymal stem cells (hMSCs) on scaffolds surface and the proliferation of cells were evaluated with Alamar Blue tests. In vitro cultivations of hMSCs showed that PLC (50:50)/BSA scaffolds supported a significantly higher proliferation rate of seeded cells than scaffolds prepared by polymer PLC (75:25)/BSA. Overall, the PLC core-shell nanofibers possessed potentially regulable mechanical properties useful for tissue engineering as well as sustained release potential for medical applications.


Asunto(s)
Fenómenos Mecánicos , Nanofibras/química , Poliésteres/química , Ingeniería de Tejidos , Andamios del Tejido/química , Proliferación Celular/efectos de los fármacos , Humanos , Ensayo de Materiales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Poliésteres/farmacología
15.
Adv Healthc Mater ; 7(5)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29205938

RESUMEN

Endothelialization, formation of endothelial cells (ECs) layer on cardiovascular implant surface, is considered an ideal approach to prevent restenosis (renarrowing of blood vessel mainly due to the accumulation of proliferated vascular smooth muscle cells, SMCs) and thrombosis. In this study, the possibility of using polyurethane (PU) as a coating platform for functionalization with peptide to enhance endothelialization on implants is explored. PUs are synthesized through metal-free organocatalytic polymerization followed by chemical conjugation with an EC-specific REDV peptide through thiol-ene reaction. Meanwhile, the free isocyanate groups of PU allow for covalent grafting of REDV-functionalized PU (PU/REDV) to silanize implant materials (nitinol and PET). PU/REDV coating with peptide grafting density of ≈2 nmol cm-2 selectively accommodates primary human umbilical vein ECs (HUVECs) and retards spreading of primary human umbilical artery SMCs (HUASMCs). In addition, a layer of HUVECs is formed within 3 d on PU/REDV-coated surfaces, while proliferation of HUASMCs is inhibited. The selectivity is further confirmed by coculture of HUVECs and HUASMCs. Moreover, the PU/REDV-coated surfaces are less thrombogenic as evidenced by reduced number and activity of adhered platelets. Therefore, PU/REDV can be potentially used as a coating of cardiovascular implants to prevent restenosis and thrombosis by promoting endothelialization.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Péptidos/química , Poliuretanos/química , Técnicas de Cocultivo , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología
16.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(4): 441-446, 2018 Aug 01.
Artículo en Zh | MEDLINE | ID: mdl-30182574

RESUMEN

Bone tissue engineering is a scientific field devoted to the development of materials that can repair or replace human bone tissue with biological and engineering methods. The stent, which provides structural support and adhesion sites for cell and tissue growth, is one of the key elements in tissue engineering. The scaffold may comprise metal, polymer, and ceramic biomaterial. The polymer scaffold is widely used due to its biocompatibility, biodegradability, and mechanical stability. Chitosan, as a natural polymer, is derived from chitin and has played a particularly important role in bone tissue engineering over the past two decades. In recent years, chitosan composites and their application in bone tissue engineering have received considerable attention due to their small foreign body reaction, excellent antibacterial properties, plasticity, suitability for inward cell growth, and bone conduction. This review will discuss the biocompatibility and osteogenesis research in vivo and in vitro of several common chitosan composites in bone tissue engineering.


Asunto(s)
Regeneración Ósea , Quitosano , Ingeniería de Tejidos , Andamios del Tejido , Materiales Biocompatibles , Huesos , Humanos
17.
Nat Commun ; 9(1): 917, 2018 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-29500445

RESUMEN

Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index-ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections.


Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana Múltiple , Sustancias Macromoleculares/uso terapéutico , Animales , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Ciego/cirugía , Modelos Animales de Enfermedad , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Cinética , Ligadura , Sustancias Macromoleculares/farmacocinética , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , Polímeros/síntesis química , Polímeros/química , Polímeros/farmacocinética , Polímeros/uso terapéutico , Punciones , Análisis de Secuencia de ARN , Distribución Tisular/efectos de los fármacos
18.
Mater Sci Eng C Mater Biol Appl ; 74: 471-477, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28254320

RESUMEN

Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control.


Asunto(s)
Portadores de Fármacos/química , Nanofibras/química , Tetraciclina/química , Liberación de Fármacos , Ácido Láctico/química , Microscopía Electrónica de Rastreo , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solventes/química , Tetraciclina/metabolismo
19.
Mater Sci Eng C Mater Biol Appl ; 70(Pt 2): 1089-1094, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27772709

RESUMEN

Nerve tissue engineering (TE) requires biomimetic scaffolds providing essential chemical and topographical cues for nerve regeneration. Poly(glycerol sebacate) (PGS) is a biodegradable and elastic polymer that has gained great interest as a TE scaffolding biomaterial. However, uncured PGS is difficult to be electrospun into nanofibers. PGS would, therefore, require the addition of electrospinning agents. In this study, we modified PGS by using atom transfer radical polymerization (ATRP) to synthesize PGS-based copolymers with methyl methacrylate (MMA). The synthesized PGS-PMMA copolymer showed a molecular weight of 82kDa and a glass transition temperature of 115°C. More importantly, the PGS-PMMA could be easily electrospun into nanofiber with a fiber diameter of 167±33nm. Blending gelatin into PGS-PMMA nanofibers was found to increase its hydrophilicity and biocompatibility. Rat PC12 cells were seeded onto the PGS-PMMA/gelatin nanofibers to investigate their potential for nerve regeneration. It was found that gelatin-containing PGS-based nanofibers promoted cell proliferation. The elongated cell morphology observed on such nanofibers indicated that the scaffolds could induce the neurite outgrowth of the nerve stem cells. Overall, our study suggested that the synthesis of PGS-based copolymers might be a promising approach to enhance their processability, and therefore advancing bioscaffold engineering for various TE applications.


Asunto(s)
Glicerol/análogos & derivados , Nanofibras/química , Tejido Nervioso/fisiología , Ingeniería de Tejidos/métodos , Animales , Proliferación Celular , Forma de la Célula , Decanoatos , Glicerol/síntesis química , Glicerol/química , Nanofibras/ultraestructura , Células PC12 , Polímeros , Polimetil Metacrilato/síntesis química , Polimetil Metacrilato/química , Espectroscopía de Protones por Resonancia Magnética , Ratas
20.
ChemSusChem ; 8(23): 3992-5, 2015 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-26592360

RESUMEN

The method used to assemble dye-sensitized photoelectrochemical (DS-PEC) devices plays a vital role in determining its photoactivity and stability. We report a simple and effective method to assemble supramolecular DS-PECs introducing PMMA as support material and a catalyst modified with long carbon chains as photoanodes. The long carbon chains in combination with PMMA allow to better immobilize the catalyst. DS-PECs obtained by this simple method have display excellent photoactivities and stabilities. A photocurrent density of 1.1 mA cm(-2) and a maximum IPCE of 9.5 % have been obtained with a 0.2 V vs NHE external bias.


Asunto(s)
Colorantes/química , Procesos Fotoquímicos , Agua/química , Catálisis , Electroquímica , Electrodos , Polimetil Metacrilato/química
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA