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1.
Biopolymers ; 109(1)2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29105737

RESUMEN

Development of bioadhesives with tunable mechanical strength, high adhesiveness, biocompatibility, and injectability is greatly desirable in all surgeries to replace or complement the sutures and staples. Herein, the dual catalytic activity of horseradish peroxidase is exploited to in situ form the hydroxyphenyl propionic acid-gelatin/thiolated gelatin (GH/GS) adhesive hydrogels including two alternative crosslinks (phenol-phenol and disulfide bonds) with fast gelation (few seconds - several minutes) and improved physicochemical properties. Their elastic moduli increase from 6.7 to 10.3 kPa by adding GS polymer that leads to the better stability of GH/GS hydrogels than GH ones. GH/GS adhesive strength is respectively 6.5-fold and 15.8-fold higher than GH-only and fibrin glue that is due to additional disulfide linkages between hydrogels and tissues. Moreover, in vitro cell study with human dermal fibroblast showed the cell-compatibility of GH/GS hydrogels. Taken together, GH/GS hydrogels can be considered as promising potential adhesive materials for various biomedical applications.


Asunto(s)
Gelatina , Hidrogeles , Animales , Gelatina/química , Gelatina/farmacología , Peroxidasa de Rábano Silvestre/química , Hidrogeles/síntesis química , Hidrogeles/química , Hidrogeles/farmacología , Porcinos , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología
2.
Molecules ; 23(4)2018 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-29601480

RESUMEN

Tissue adhesives based on polyamidoamine (PAMAM) dendrimer, grafted with UV-sensitive aryldiazirine (PAMAM-g-diazirine) are promising new candidates for light active adhesion on soft tissues. Diazirine carbene precursors form interfacial and intermolecular covalent crosslinks with tissues after UV light activation that requires no premixing or inclusion of free radical initiators. However, primary amines on the PAMAM dendrimer surface present a potential risk due to their cytotoxic and immunological effects. PAMAM-g-diazirine formulations with cationic pendant amines converted into neutral amide groups were evaluated. In vitro toxicity is reduced by an order of magnitude upon amine capping while retaining bioadhesive properties. The in vivo immunological response to PAMAM-g-diazirine formulations was found to be optimal in comparison to standard poly(lactic-co-glycolic acid) (PLGA) thin films.


Asunto(s)
Reactivos de Enlaces Cruzados/química , Dendrímeros/química , Diazometano/química , Membranas Artificiales , Adhesivos Tisulares , Rayos Ultravioleta , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química
3.
Biomacromolecules ; 17(1): 237-45, 2016 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-26674175

RESUMEN

Silk fibroin from the domesticated silkworm Bombyx mori is a naturally occurring biopolymer with charged hydrophilic terminal regions that end-cap a hydrophobic core consisting of repeating sequences of glycine, alanine, and serine residues. Taking inspiration from mussels that produce proteins rich in L-3,4-dihydroxyphenylalanine (DOPA) to adhere to a variety of organic and inorganic surfaces, the silk fibroin was functionalized with catechol groups. Silk fibroin was selected for its high molecular weight, tunable mechanical and degradation properties, aqueous processability, and wide availability. The synthesis of catechol-functionalized silk fibroin polymers containing varying amounts of hydrophilic polyethylene glycol (PEG, 5000 g/mol) side chains was carried out to balance silk hydrophobicity with PEG hydrophilicity. The efficiency of the catechol functionalization reaction did not vary with PEG conjugation over the range studied, although tuning the amount of PEG conjugated was essential for aqueous solubility. Adhesive bonding and cell compatibility of the resulting materials were investigated, where it was found that incorporating as little as 6 wt % PEG prior to catechol functionalization resulted in complete aqueous solubility of the catechol conjugates and increased adhesive strength compared with silk lacking catechol functionalization. Furthermore, PEG-silk fibroin conjugates maintained their ability to form ß-sheet secondary structures, which can be exploited to reduce swelling. Human mesenchymal stem cells (hMSCs) proliferated on the silks, regardless of PEG and catechol conjugation. These materials represent a protein-based approach to catechol-based adhesives, which we envision may find applicability as biodegradable adhesives and sealants.


Asunto(s)
Materiales Biocompatibles/síntesis química , Fibroínas/síntesis química , Células Madre Mesenquimatosas/fisiología , Adhesivos Tisulares/síntesis química , Animales , Bivalvos , Bombyx , Células Cultivadas , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Polietilenglicoles/química , Estructura Secundaria de Proteína , Proteínas/metabolismo , Seda/química
4.
J Mater Sci Mater Med ; 27(2): 30, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26704547

RESUMEN

Marine mussels tightly adhering to various underwater surfaces inspires human to design adhesives for wet tissue adhesion in surgeries. Characterization of mussel adhesive plaques describes a matrix of proteins containing 3,4-dihydroxyphenylalanine (DOPA), which provides strong adhesion in aquatic conditions. Several synthetic polymer systems have been developed based on this DOPA chemistry. Herein, a citrate-based tissue adhesives (POEC-d) was prepared by a facile one-pot melt polycondensation of two diols including 1,8-octanediol and poly(ethylene oxide) (PEO), citric acid (CA) and dopamine, and the effects of hydrophilic and soft PEO on the properties of adhesives were studied. It was found that the obtained adhesives exhibited water-soluble when the mole ratio of PEO to 1,8-octanediol was 70%, and the equilibrium swelling percentage of cured adhesive was about 144%, and degradation rate was in the range of 1-2 weeks. The cured adhesives demonstrated soft rubber-like behavior. The lap shear adhesion strength measured by bonding wet pig skin was in the range of 21.7-33.7 kPa, which was higher than that of commercial fibrin glue (9-15 kPa). The cytotoxicity tests showed the POEC-d adhesives had a low cytotoxicity. Our results supports that POEC-d adhesives, which combined strong wet adhesion with good biodegradability, acceptable swelling ratio, good elasticity and low cytotoxicity, have potentials in surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used.


Asunto(s)
Materiales Biomiméticos , Bivalvos/química , Catecoles/química , Ácido Cítrico/química , Polietilenglicoles/química , Adhesivos Tisulares , Animales , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citratos/síntesis química , Citratos/química , Citratos/farmacología , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiología , Ensayo de Materiales , Polímeros/síntesis química , Polímeros/química , Polímeros/farmacología , Resistencia al Corte/efectos de los fármacos , Piel/citología , Piel/efectos de los fármacos , Porcinos , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología
5.
Molecules ; 19(5): 6220-7, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24838075

RESUMEN

Alkyl cyanoacrylates are interesting products for use in industry because of their properties enabling them to stick together a wide range of substrates. n-Butyl cyanoacrylate is one of the most successfully used tissue adhesives in the field of medicine because it exhibits bacteriostatic and haemostatic characteristics, in addition to its adhesive properties. At present, its synthesis is performed with good yields via Knoevenagel condensation using conventional sources of heating, but this requires a long processing time. The aim of this work was to look for a new way of synthesising n-butyl cyanoacrylate using microwave irradiation as the source of heating. This non-conventional source of heating most likely reduces the process time of the synthesis. In comparison with a conventional heating source, such as an oil bath, the results showed the advantages of this method whereby the n-butyl cyanoacrylate gave the same yield and quality with a reduction in the reaction time by a factor of 3-5-fold.


Asunto(s)
Enbucrilato/síntesis química , Adhesivos Tisulares/síntesis química , Enbucrilato/química , Humanos , Microondas , Adhesivos Tisulares/química , Cicatrización de Heridas/efectos de los fármacos
6.
AAPS PharmSciTech ; 13(3): 990-1004, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22806818

RESUMEN

Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia.


Asunto(s)
Compuestos de Calcio/síntesis química , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Tracto Gastrointestinal/efectos de los fármacos , Metilcelulosa/análogos & derivados , Quinazolinas/síntesis química , Silicatos/síntesis química , Animales , Compuestos de Calcio/administración & dosificación , Compuestos de Calcio/metabolismo , Tracto Gastrointestinal/metabolismo , Derivados de la Hipromelosa , Masculino , Metilcelulosa/administración & dosificación , Metilcelulosa/síntesis química , Metilcelulosa/metabolismo , Quinazolinas/administración & dosificación , Quinazolinas/metabolismo , Ratas , Silicatos/administración & dosificación , Silicatos/metabolismo , Adhesivos Tisulares/administración & dosificación , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/metabolismo
7.
Carbohydr Polym ; 278: 119000, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-34973802

RESUMEN

Designing adhesive hydrogel wound dressings with inherent antibacterial and antioxidant properties is desirable to treat cutaneous full-thickness injuries in clinical care. Herein, a series of photo-induced Schiff base crosslinking-based adhesive hydrogels with promising traits are designed and prepared through Diels-Alder (DA) reactions between functional groups-grafted carboxymethyl chitosan (CMCS) and a photo-responsive polyethylene glycol (PEG) crosslinker. The quaternary ammonium and phenol groups in modified CMCS endows hydrogels excellent antibacterial and antioxidant properties. Upon UV (365 nm) irradiation, the generated o-nitrosobenzaldehyde from the photo-isomerization of o-nitrobenzyl in PEG derivative can subsequently crosslink with amino groups on tissue interfaces via Schiff base, endowing the hydrogel with well adhesiveness. Additionally, the hydrogel exhibits good BSA adsorption capacity, cytocompatibility and hemostatic property. The in vivo full-thickness skin defect study on mice indicates that the multi-functional hydrogel with considerable collagen deposition and vascularization capacities can be an effective and promising adhesive dressing for improving wound healing.


Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Quitosano/análogos & derivados , Hidrogeles/farmacología , Adhesivos Tisulares/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antioxidantes/síntesis química , Antioxidantes/química , Compuestos de Bifenilo/antagonistas & inhibidores , Pollos , Quitosano/síntesis química , Quitosano/química , Quitosano/farmacología , Escherichia coli/efectos de los fármacos , Femenino , Hidrogeles/síntesis química , Hidrogeles/química , Ratones , Ratones Endogámicos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Células 3T3 NIH , Tamaño de la Partícula , Procesos Fotoquímicos , Picratos/antagonistas & inhibidores , Piel/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Porcinos , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química , Rayos Ultravioleta
8.
Biomacromolecules ; 12(12): 4326-34, 2011 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-22059927

RESUMEN

Mussel-inspired adhesive hydrogels represent innovative candidate medical sealants or glues. In the present work, we describe an enzyme-degradable mussel-inspired adhesive hydrogel formulation, achieved by incorporating minimal elastase substrate peptide Ala-Ala into the branched poly(ethylene glycol) (PEG) macromonomer structure. The system takes advantage of neutrophil elastase expression upregulation and secretion from neutrophils upon recruitment to wounded or inflamed tissue. By integrating adhesive degradation behaviors that respond to cellular cues, we expand the functional range of our mussel-inspired adhesive hydrogel platforms. Rapid (<1 min) and simultaneous gelation and adhesion of the proteolytically active, catechol-terminated precursor macromonomer was achieved by addition of sodium periodate oxidant. Rheological analysis and equilibrium swelling studies demonstrated that the hydrogel is appropriate for soft tissue-contacting applications. Notably, hydrogel storage modulus (G') achieved values on the order of 10 kPa, and strain at failure exceeded 200% strain. Lap shear testing confirmed the material's adhesive behavior (shear strength: 30.4 ± 3.39 kPa). Although adhesive hydrogel degradation was not observed during short-term (27 h) in vitro treatment with neutrophil elastase, in vivo degradation proceeded over several months following dorsal subcutaneous implantation in mice. This work represents the first example of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of this family of materials.


Asunto(s)
Hidrogeles/síntesis química , Elastasa de Leucocito/metabolismo , Adhesivos Tisulares/síntesis química , Alanina/química , Animales , Bivalvos/metabolismo , Adhesión Celular , Hidrogeles/química , Elastasa de Leucocito/biosíntesis , Masculino , Ratones , Neutrófilos/inmunología , Polietilenglicoles/química , Reología , Adhesivos Tisulares/química
9.
Biomacromolecules ; 12(7): 2653-9, 2011 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-21599012

RESUMEN

Bioinspired from adhesion behaviors of mussels, injectable and thermosensitive chitosan/Pluronic composite hydrogels were synthesized for tissue adhesives and hemostatic materials. Chitosan conjugated with multiple catechol groups in the backbone was cross-linked with terminally thiolated Pluronic F-127 triblock copolymer to produce temperature-sensitive and adhesive sol-gel transition hydrogels. A blend mixture of the catechol-conjugated chitosan and the thiolated Pluronic F-127 was a viscous solution state at room temperature but became a cross-linked gel state with instantaneous solidification at the body temperature and physiological pH. The adhesive chitosan/Pluronic injectable hydrogels with remnant catechol groups showed strong adhesiveness to soft tissues and mucous layers and also demonstrated superior hemostatic properties. These chitosan/Pluronic hydrogels are expected to be usefully exploited for injectable drug delivery depots, tissue engineering hydrogels, tissue adhesives, and antibleeding materials.


Asunto(s)
Reactivos de Enlaces Cruzados/administración & dosificación , Hemostáticos/administración & dosificación , Hidrogeles/administración & dosificación , Adhesivos Tisulares/administración & dosificación , Animales , Materiales Biocompatibles , Catecoles/administración & dosificación , Catecoles/química , Quitosano/administración & dosificación , Quitosano/química , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/química , Hemostáticos/síntesis química , Hemostáticos/química , Hidrogeles/síntesis química , Hidrogeles/química , Concentración de Iones de Hidrógeno , Inyecciones Subcutáneas , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Estructura Molecular , Poloxámero/administración & dosificación , Poloxámero/química , Ratas , Ratas Sprague-Dawley , Temperatura , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química
10.
J Mater Chem B ; 9(30): 5954-5966, 2021 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-34254103

RESUMEN

In recent years, multifunctional hydrogels have garnered great interest. Usually, there is a contradiction between the toughness and interface adhesion of traditional hydrogels. In engineering and medical applications, hydrogels need to have good adhesive properties and toughness. The design of functional hydrogels with strong adhesion and high toughness is key to their application. In this review, the research progress of adhesive and tough hydrogels in recent years is outlined. Specifically, the structural design (such as integrated, layered, and gradient structures) and applications (such as cartilage repair, drug delivery, strain sensors, tissue adhesives, soft actuators, and supercapacitors) of adhesive and tough hydrogels are classified and discussed, providing new insights on their design and development.


Asunto(s)
Diseño de Fármacos , Hidrogeles/síntesis química , Adhesivos Tisulares/síntesis química , Humanos , Hidrogeles/química , Adhesivos Tisulares/química
11.
Int J Biol Macromol ; 192: 1344-1356, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34536477

RESUMEN

Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and ß-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ±â€¯214.9, and 3722.2 ±â€¯486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.


Asunto(s)
Acrilatos/química , Materiales Biocompatibles/química , Colágeno/química , Gelatina/química , Poliuretanos/química , Adhesivos Tisulares/química , Animales , Fenómenos Químicos , Técnicas de Química Sintética , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Estructura Molecular , Ratas , Adhesivos Tisulares/síntesis química , Ingeniería de Tejidos
12.
Carbohydr Polym ; 271: 118428, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34364568

RESUMEN

Emergent and long-term hemorrhage control is requisite and beneficial for reducing global mortality and postoperative complications (e.g., second bleeding and adverse tissue adhesion). Despite recent advance in injectable hydrogels for hemostasis, achieving rapid gelation, strong tissue-adhesive property and stable mechanical strength under fluid physiological environment is still challenging. Herein, we developed a novel chitosan hydrogel (CCS@gel) via dynamic Schiff base reaction and mussel-inspired catechol chemistry. The hydrogel possessed high gelation rate (<10 s), strong wet adhesiveness, excellent self-healing performance and biocompatibility. More importantly, the CCS@gel exhibited saline-induced contractile performance and mechanical enhancement, promoting its mechanical property in moist internal conditions. In vivo studies demonstrated its superior hemostatic efficacy for diverse anticoagulated visceral and carotid bleeding scenarios, compared to commercialized fibrin glue. The hydrogel-treated rats survived for 8 weeks with minimal inflammation and postoperative adhesion. These results revealed that the promising CCS@gel would be a facile, efficient and safe sealant for clinical hemorrhage control.


Asunto(s)
Quitosano/farmacología , Hemorragia/terapia , Hemostáticos/farmacología , Hidrogeles/farmacología , Adhesivos Tisulares/farmacología , Cicatrización de Heridas/efectos de los fármacos , Adhesividad , Animales , Vendajes , Traumatismos de las Arterias Carótidas/terapia , Quitosano/síntesis química , Técnicas Hemostáticas/instrumentación , Hemostáticos/síntesis química , Hidrogeles/síntesis química , Hígado/lesiones , Masculino , Polietilenglicoles/síntesis química , Polietilenglicoles/farmacología , Ratas Sprague-Dawley , Bases de Schiff/síntesis química , Bases de Schiff/farmacología , Bazo/lesiones , Adhesivos Tisulares/síntesis química , Técnicas de Cierre de Heridas/instrumentación
13.
Carbohydr Polym ; 261: 117810, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33766329

RESUMEN

Chitosan-based hydrogels have been widely used for various biomedical applications due to their versatile properties such as biocompatibility, biodegradability, muco-adhesiveness, hemostatic effect and so on. However, the inherent rigidity and brittleness of pure chitosan hydrogels are still unmanageable, which has limited their potential use in biomaterial research. In this study, we developed in situ forming chitosan/PEG hydrogels with improved mechanical properties, using the enzymatic crosslinking reaction of horseradish peroxidase (HRP). The effect of PEG on physico-chemical properties of hybrid hydrogels was thoroughly elucidated by varying the content (0-100 %), molecular weight (4, 10 and 20 kDa) and geometry (linear, 4-arm) of the PEG derivatives. The resulting hydrogels demonstrated excellent hemostatic ability and are highly biocompatible in vivo, comparable to commercially available fibrin glue. We suggest these chitosan/PEG hybrid hydrogels with tunable physicochemical and tissue adhesive properties have great potential for a wide range of biomedical applications in the near future.


Asunto(s)
Quitosano/química , Hidrogeles/síntesis química , Adhesivos Tisulares , Adhesividad , Animales , Células Cultivadas , Dermis/citología , Dermis/efectos de los fármacos , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Hemostasis/efectos de los fármacos , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Inyecciones , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Polimerizacion , Polímeros/administración & dosificación , Polímeros/síntesis química , Polímeros/química , Polímeros/farmacología , Ratas , Ratas Sprague-Dawley , Estrés Mecánico , Adhesivos Tisulares/administración & dosificación , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Ingeniería de Tejidos/métodos
14.
AAPS PharmSciTech ; 11(2): 793-808, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20446071

RESUMEN

The purpose of this study was to develop and evaluate the bioadhesivity, in vitro drug release, and permeation of an intravaginal bioadhesive polymeric device (IBPD) loaded with 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Modified polyamide 6,10, poly(lactic-coglycolic acid), polyacrylic acid, polyvinyl alcohol, and ethylcellulose were blended with model drugs AZT and PSS as well as radio-opaque barium sulfate (BaSO4) and then compressed into caplet devices on a tableting press. One set of devices was coated with 2% w/v pentaerythritol polyacrylic acid (APE-PAA) while another remained uncoated. Thermal analysis was performed on the constituent polymers as well the IBPD. The changes in micro-environmental pH within the simulated human vaginal fluid due to the presence of the IBPD were assessed over a period of 30 days. Textural profile analysis indicated that the bioadhesivity of the APE-PAA-coated devices (3.699 +/- 0.464 N; 0.0098 +/- 0.0004 J) was higher than that of the uncoated devices (1.198 +/- 0.150 N; 0.0019 +/- 0.0001 J). In addition, BaSO4-facilitated X-ray imaging revealed that the IBPD adhered to pig vaginal tissue over the experimental period of 30 days. Controlled drug release kinetics was obtained over 72 days. During a 24-h permeation study, an increase in drug flux for both AZT (0.84 mg cm(-2) h(-1)) and PSS (0.72 mg cm(-2) h(-1)) was realized up to 12 h and thereafter a steady-state was achieved. The diffusion and dissolution dynamics were mechanistically deduced based on a chemometric and molecular structure modeling approach. Overall, results suggested that the IBPD may be sufficiently bioadhesive with desirable physicochemical and physicomechanical stability for use as a prolonged intravaginal drug delivery device.


Asunto(s)
Preparaciones de Acción Retardada/síntesis química , Adhesivos Tisulares/síntesis química , Vagina/química , Zidovudina/administración & dosificación , Zidovudina/química , Adhesividad , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/química , Difusión , Composición de Medicamentos/métodos , Femenino , Propiedades de Superficie , Porcinos , Resistencia a la Tracción
15.
Biomater Sci ; 8(5): 1240-1255, 2020 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-31984389

RESUMEN

Mussels are well-known for their extraordinary capacity to adhere onto different surfaces in various hydrophillic conditions. Their unique adhesion ability under water or in wet conditions has generated considerable interest towards developing mussel inspired polymeric systems that can mimic the chemical mechanisms used by mussels for their adhesive properties. Catechols like 3,4-dihydroxy phenylalanine (DOPA) and their biochemical interactions have been largely implicated in mussels' strong adhesion to various substrates and have been the centerpoint of research and development efforts towards creating superior tissue adhesives for surgical and tissue engineering applications. In this article, we review bioadhesion and adhesives from an engineering standpoint, specifically the requirements of a good tissue glue, the relevance that DOPA and other catechols have in tissue adhesion, current trends in mussel-inspired bioadhesives, strategies to develop mussel-inspired tissue glues, and perspectives for future development of these materials.


Asunto(s)
Materiales Biomiméticos/química , Atención a la Salud , Adhesivos Tisulares/química , Ingeniería de Tejidos , Animales , Materiales Biomiméticos/síntesis química , Bivalvos , Humanos , Adhesivos Tisulares/síntesis química
16.
Mater Sci Eng C Mater Biol Appl ; 111: 110796, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32279807

RESUMEN

Tissue adhesives have emerged as an effective method for wound closure and hemostasis in recent decades, due to their ability to bond tissues together, preventing separation from one tissue to another. However, existing tissue adhesives still have several limitations. Tremendous efforts have been invested into developing new tissue adhesives by improving upon existing adhesives through different strategies. Therefore, highlighting and analyzing these design strategies are essential for developing the next generation of advanced adhesives. To this end, we reviewed the available strategies for modifying traditional adhesives (including cyanoacrylate glues, fibrin sealants and BioGlue), as well as design of emerging adhesives (including gelatin sealants, methacrylated sealants and bioinspired adhesives), focusing on their structures, adhesive mechanisms, advantages, limitations, and current applications. The bioinspired adhesives have numerous advantages over traditional adhesives, which will be a wise direction for achieving tissue adhesives with superior properties.


Asunto(s)
Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/farmacología , Animales , Cianoacrilatos/farmacología , Adhesivo de Tejido de Fibrina/farmacología , Hemostasis/efectos de los fármacos , Humanos , Cicatrización de Heridas/efectos de los fármacos
17.
Carbohydr Polym ; 237: 116138, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32241433

RESUMEN

Schiff base reaction crosslinking hydrogels are advantageous by rapid formation and absence of external crosslinkers. However, poor mechanical hindered their broader applications. Here, a mechanically strengthened tissue adhesive was constructed through incorporation of chitin nano-whiskers (CtNWs) with a Schiff base crosslinking hydrogel of carboxymethyl chitosan (CMCS) and dextran dialdehyde (DDA). The optimal formulation of complexed hydrogel exhibited 1.87 folds higher compressive stress than non-complexed and 1.51 time higher adhesive strength on porcine skin. The complexed hydrogel exhibited negligible cytotoxicity, anti-swelling performance in PBS, optimum antibacterial and hemostatic capacities. In vivo implantation studies confirmed the complexed hydrogel was degradable without long-term inflammatory responses. Desirable efficacy of injectable complexed hydrogel as hemostat was demonstrated in rat liver injury model, which could avoid severe postoperative adhesion and necrosis as observed in the treatment with commercial 3 M™ vetbond™ tissue adhesive. The results highlighted that the complexed hydrogel potentiated rapid hemostasis and wound repair applications.


Asunto(s)
Materiales Biocompatibles , Hidrogeles , Adhesivos Tisulares , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Quitosano/análogos & derivados , Quitosano/química , Fuerza Compresiva , Dextranos/química , Hemostáticos/síntesis química , Hemostáticos/química , Hidrogeles/síntesis química , Hidrogeles/química , Ratas , Porcinos , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química
18.
J Mater Chem B ; 8(36): 8282-8293, 2020 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-32785356

RESUMEN

Hemorrhage remains one of the direct causes of high mortality. The development of ideal hemostatic materials with sound ability to deal with severe wound is urgent needed. Although starch-based hemostatic powder has been widely used, hydrous physiological environments severely hamper its binding to the target tissue, thereby limiting the effectiveness in hemostasis. Herein, inspired by mussel adhesive protein, a novel injectable tissue-adhesive hydrogel (St-Dopa hydrogel) composed of starch, succinic anhydride and dopamine was developed in situ by enzymatic crosslinking. The results show that St-Dopa hydrogels were intimately integrated with biological tissue and formed robust barriers to reduce blood loss. St-Dopa hydrogels exhibited superior capacity for in vitro and in vivo hemostasis as compared with chitin hydrogels. In addition to the ease of operation, St-Dopa hydrogels exhibited rapid sol-gel transition, porous microscopic morphology, good swelling ratio and biodegradability, tissue-like elastomeric mechanical properties and excellent cyto/hemo-compatibility. These results suggest that this newly developed St-Dopa hydrogel is a promising biological adhesive and hemostatic material.


Asunto(s)
Hemorragia/tratamiento farmacológico , Hemostasis/efectos de los fármacos , Hemostáticos/uso terapéutico , Hidrogeles/uso terapéutico , Almidón/uso terapéutico , Adhesivos Tisulares/uso terapéutico , Animales , Línea Celular , Dopamina/análogos & derivados , Dopamina/uso terapéutico , Dopamina/toxicidad , Módulo de Elasticidad , Hemostáticos/síntesis química , Hemostáticos/toxicidad , Hidrogeles/síntesis química , Hidrogeles/toxicidad , Masculino , Ensayo de Materiales , Ratones , Porosidad , Conejos , Almidón/análogos & derivados , Almidón/toxicidad , Anhídridos Succínicos/química , Anhídridos Succínicos/uso terapéutico , Anhídridos Succínicos/toxicidad , Porcinos , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/toxicidad , Sustancias Viscoelásticas/síntesis química , Sustancias Viscoelásticas/uso terapéutico , Sustancias Viscoelásticas/toxicidad
19.
Biomater Sci ; 8(10): 2878-2886, 2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-32296788

RESUMEN

Tuning the configuration of lanthanide-doped upconversion nanoparticles (UCNPs) has been proven to be an effective approach to enhance upconversion (UC) efficiency, especially for neodymium (Nd3+)-sensitized UCNPs. Rational configuration design can spatially separate activators and sensitizers, achieving the evolution from single core to multilayer structures. However, optimizing multiphoton UC emission via configuration modulation, especially in the ultraviolet range, is yet to be fully investigated. In this work, thickness tuning of the sensitizing layer containing Nd3+ ions and the inert layer containing gadolinium ions at a fixed combined thickness of 5 nm in tetralayer UCNPs to exclude the size effect is reported for the first time. The optimal thickness of sensitizing and inert layers was determined to be 3 and 2 nm respectively, showing a new strategy of balancing sensitization and surface passivation to enhance 4-photon (360 nm) emission. Although 3-photon emission (475 nm) is mainly influenced by the overall size, its emission intensity remains similar in all the tetralayer UCNPs. Additionally, an 808 nm cross-linked hydrogel has been demonstrated as a potential near-infrared activated tissue sealant. Our results have uncovered the structural parameters for optimal ultraviolet UC emissions and elucidated the strategic importance of nano-configuration design to minimize the energy loss in the high-photon UC process.


Asunto(s)
Reactivos de Enlaces Cruzados/química , Hidrogeles/química , Nanopartículas/química , Neodimio/química , Adhesivos Tisulares/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/farmacología , Humanos , Hidrogeles/síntesis química , Hidrogeles/farmacología , Rayos Infrarrojos , Estructura Molecular , Tamaño de la Partícula , Propiedades de Superficie , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/farmacología , Rayos Ultravioleta
20.
Colloids Surf B Biointerfaces ; 188: 110737, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32004904

RESUMEN

Wound dressing materials are widely used to protect wounds from the external environment and to promote wound healing. However, conventional wound dressings lack tissue adhesive properties and anti-inflammatory functions, which lead to fibrosis and stricture, in cases such as gastrointestinal wounds after endoscopic surgery. In the current study, we report tissue-adhesive and anti-inflammatory properties of a wound dressing composed of corticosteroid-modified gelatin particles. Hydrocortisone (HC), which is a class of anti-inflammatory corticosteroid, was used to modify Alaska-pollock gelatin (ApGltn) to synthesize HC-modified ApGltn (HC-ApGltn). Microparticles (MPs) of HC-ApGltn were fabricated by adding ethanol in HC-ApGltn aqueous solution and performing thermal crosslinking (TC) without the use of toxic surfactants and crosslinking reagents. Modification of ApGltn with hydrophobic HC containing cholesterol backbone structure improved its adhesion strength to gastric submucosal tissues under wet conditions owing to hydrophobic interactions. This retention of adhesive property under wet conditions allows for stable protection of wounds from the external environment. We found that HC-ApGltn MPs were taken up by macrophages and they effectively suppressed morphological changes of LPS-activated macrophages and the expression level of the inflammatory cytokine. Robust tissue adhesive and anti-inflammatory MPs may serve as an advanced wound dressing that can protect wounds and suppress inflammatory responses for promoting wound healing.


Asunto(s)
Antiinflamatorios/farmacología , Diseño de Fármacos , Gelatina/farmacología , Hidrocortisona/farmacología , Adhesivos Tisulares/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Línea Celular , Gelatina/síntesis química , Gelatina/química , Hidrocortisona/síntesis química , Hidrocortisona/química , Ratones , Conformación Molecular , Tamaño de la Partícula , Propiedades de Superficie , Adhesivos Tisulares/síntesis química , Adhesivos Tisulares/química
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