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1.
Mussel-inspired silver-releasing antibacterial hydrogels   总被引:1,自引:0,他引:1  
A silver-releasing antibacterial hydrogel was developed that simultaneously allowed for silver nanoparticle formation and gel curing. Water-soluble polyethylene glycol (PEG) polymers were synthesized that contain reactive catechol moieties, inspired by mussel adhesive proteins, where the catechol containing amino acid 3,4-dihydroxyphenylalanine (DOPA) plays an important role in the ability of the mussel to adhere to almost any surface in an aqueous environment. We utilized silver nitrate to oxidize polymer catechols, leading to covalent cross-linking and hydrogel formation with simultaneous reduction of Ag(I). Silver release was sustained for periods of at least two weeks in PBS solution. Hydrogels were found to inhibit bacterial growth, consistent with the well-known antibacterial properties of silver, while not significantly affecting mammalian cell viability. In addition, thin hydrogel films were found to resist bacterial and mammalian cell attachment, consistent with the antifouling properties of PEG. We believe these materials have a strong potential for antibacterial biomaterial coatings and tissue adhesives, due to the material-independent adhesive properties of catechols.  相似文献   

2.
The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.  相似文献   

3.
Sphingosine-1-phosphate (S1P), a bioactive lipid, is a potent candidate for treatment of ischemic vascular disease. However, designing biomaterial systems for the controlled release of S1P to achieve therapeutic angiogenesis presents both biological and engineering challenges. Thus, the objective of this study was to design a hydrogel system that provides controlled and sustained release of S1P to establish local concentration gradients that promote neovascularization. Alginate hydrogels have been extensively studied and characterized for delivery of proangiogenic factors. We sought to explore if chitosan (0, 0.1, 0.5, or 1%) incorporation could be used as a means to control S1P release from alginate hydrogels. With increasing chitosan incorporation, hydrogels exhibited significantly denser pore structure and stiffer material properties. While 0.1 and 0.5% chitosan gels demonstrated slower respective release of S1P, release from 1% chitosan gels was similar to alginate gels alone. Furthermore, 0.5% chitosan gels induced greater sprouting and directed migration of outgrowth endothelial cells (OECs) in response to released S1P under hypoxia in vitro. Overall, this report presents a platform for a novel alginate-chitosan hydrogel of controlled composition and in situ gelation properties that can be used to control lipid release for therapeutic applications.  相似文献   

4.
5.
Hydrogels were prepared using polyvinyl pyrrolidone (PVP) blended with carrageenan by gamma irradiation at different doses of 25 and 40 kGy. Gel fraction of hydrogels prepared using 10 and 15% PVP in combination with 0.25 and 0.5% carrageenan was evaluated. Based on gel fraction, 15% PVP in combination with 0.25% carrageenan and radiation dose of 25 kGy was selected for the preparation of hydrogels with nanosilver. Radiolytic synthesis of silver nanoparticles within the PVP hydrogel was carried out. The hydrogels with silver nanoparticles were assessed for antimicrobial effectiveness and physical properties of relevance to clinical performance. Fluid handling capacity (FHC) for PVP/carrageenan was 2.35 ± 0.39–6.63 ± 0.63 g/10 cm2 in 2–24 h. No counts for Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans were observed in the presence of hydrogels containing 100 ppm nanosilver after 3–6 h. The release of silver from hydrogels containing 100 ppm nanosilver was 20.42 ± 1.98 ppm/100 cm2 in 24 h. Hydrogels containing 100 ppm nanosilver with efficient FHC demonstrated potential microbicidal activity (≥3 log10 decrease in CFU/ml) against wound pathogens, P. aeruginosa, S. aureus, E. coli, and C. albicans. PVP/carrageenan hydrogels containing silver nanoparticles can be used as wound dressings to control infection and facilitate the healing process for burns and other skin injuries.  相似文献   

6.
Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H(2)O(2) hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (< 1.5%). Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm(3)) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post-exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal re-epithelialization and wound healing. Histology studies of skin showed that doxycycline loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in an SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries.  相似文献   

7.
Hybrid magnetic hydrogels are of interest for applications in biomedical science as controlled drug-delivery systems. We have developed a strategy to obtain novel hybrid hydrogels with magnetic nanoparticles (NPs) of CoFe2O3 and Fe3O4 as crosslinker agents of carboxymethylcellulose (CMC) or hyaluronic acid (HYAL) polymers and we have tested these systems for controlled doxorubicin release. The magnetic NPs are functionalized with (3-aminopropyl)trimethoxysilane (APTMS) in order to introduce amino groups on the surface. The amino coating is determined and quantified by standard Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy methods, and by cyclic voltammetry, a novel approach that permits us to look at the solution properties of the functionalized NPs. The gel formation involves the creation of an amide bond between the carboxylic groups of CMC or HYAL and the amine groups of functionalized NPs, which work as crosslinking agents of the polymer chains. The hybrid hydrogels are chemically and morphologically characterized. The rheological and the water uptake properties of the hydrogels are also investigated. Under the application of an alternating magnetic field, the CMC–HYAL hybrid hydrogel previously loaded with doxorubicin shows a drug release greater than that showed by the CMC–HYAL hydrogel crosslinked with 1,3-diaminopropane. In conclusion, the presence of magnetic NPs makes the synthesized hybrid hydrogels suitable for application as a drug-delivery system by means of alternating magnetic fields.  相似文献   

8.
Novel nanocomposite hydrogels composed of hyaluronan (HA), poly(vinyl alcohol) (PVA) and silver nanoparticles were prepared by several cycles of freezing and thawing. The nanocomposite was then characterised using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), wide-angle X-ray diffraction (XRD) and scanning electron microscopy (SEM). The complex hydrogels consisted of semi-interpenetrating network structures, with PVA microcrystallines as junction zones. By increasing the HA content, the crystallinity and melting temperature of the complex hydrogels decreased, whereas the glass transition temperatures of these materials increased because of the steric hindrance of HA and the occurrence of intermolecular interactions through hydrogen bonding between HA and PVA in the complex hydrogels. Swelling studies showed that in comparison with the swelling properties of the cryogels from PVA alone, those of the complex hydrogels can be significantly improved and presented in a pH-sensitive manner. In addition, silver nanoparticles were synthesised through UV-initiated photoreduction with HA functioning as a reducing agent and stabiliser. The silver nanoparticles were then incorporated in situ into the HA/PVA complex hydrogel matrix. The size and morphology of the as-prepared Ag nanoparticles were investigated through ultraviolet–visible light spectroscopy, transmission electron microscopy, XRD and thermogravimetric analysis. The experimental results indicated that silver nanoparticles 20–50?nm in size were uniformly dispersed in the hydrogel matrix. The antibacterial effects of the HA/PVA/Ag nanocomposite hydrogel against Escherichia coli were evaluated. The results show that this nanocomposite hydrogel possesses high antibacterial property and has a potential application as a wound dressing material.  相似文献   

9.
Wound pH strongly influences residence time and activity of various growth factors during wound healing. Hence, a pH-responsive sustained release growth factor delivery system could be beneficial for effective treatment of wound. In this context, an effort was made to evaluate the potential of a poly(N-isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery. The polymer was synthesized via radical copolymerization and influence of pH on lower critical solution temperature (LCST), microarchitechture and swelling of the hydrogel was evaluated. Results showed a pH-dependent variation in the physical properties of the hydrogel within the wound pH range. Fluorescence recovery after photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of the BSA in the hydrogel. Later, release of bovine serum albumin (BSA), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v) from the hydrogel within the range of wound pH (pH 6.7–7.9) were examined. Analysis showed non-Fickian release of therapeutics from the hydrogel with a significant variation in release rate and cumulative release with the increase in pH. Retention of the bioactivity of the released EGF was confirmed by studying murine dermal fibroblast cell proliferation in vitro. Finally, a growth factor (EGF or VEGF)-loaded hydrogel was applied on a murine excisional wound model and showed augmentation of wound healing in comparison to conventional sustained release growth factor therapy.  相似文献   

10.
The complicated synthesis procedure and limited preparation size of hydrogel inhibit its clinical application. Therefore, a facile preparation method for large-size hydrogel is required. In this study, a series of curcumin (Cur)/polyvinyl alcohol (PVA) hydrogel in a large size with different Cur concentrations is prepared by a facile physical-chemical crosslinking. The physicochemical properties, antibacterial performance and accelerating wound healing ability are evaluated with the aim of attaining a novel and effective wound dressing. The results show that the as-prepared hydrogel with the optimal Cur to PVA volume ratio of 1:5 (20% Cur/PVA) exhibits the best antibacterial abilities to E. coli (85.6%) and S. aureus (97%) than other hydrogels. When the volume ratio of Cur to PVA is 1:10 (10% Cur/PVA), the hydrogel can significantly accelerate the wound healing in rats, and successfully reconstruct intact and thickened epidermis during 14 day of healing of impaired wounds after histological examination. In one word, the present approach can shed new light on designing new type of hydrogels with promising applications in wound dressing.  相似文献   

11.
A family of injectable, biodegradable and thermosensitive co-polymer nanoparticle (NP) hydrogels based on mPEG-b-POA-b-mPEG, which was synthesized from mono-methoxy poly(ethylene glycol) (mPEG) and poly(octadecanedioic anhydride) (POA), was investigated in this paper. It was found that the aqueous dispersions of these NPs underwent a reversible gel–sol transition upon temperature change. By using paclitaxel and Bovine serum albumin (BSA) as model drugs, we noticed that the in vitro releases of both in situ gel-forming formulations were sustained and no initial burst releases were observed for 7 days. In vitro cytotoxicity tests via MTT assay indicate that mPEG-b-POA-b-mPEG NPs are non-toxic to normal mouse lung fibroblast cells (L929). The in vivo hydrogel formation and in vivo biocompatibility of co-polymer NP hydrogel were also investigated and the results further validate the biocompatible nature of co-polymer NP hydrogel. In conclusion, our mPEG-b-POA-b-mPEG NP hydrogel is able to control the release of incorporated drug for longer duration.  相似文献   

12.
Abstract

In this study, hydrogels composed of polyethyleneimine (PEI) and poly(vinyl pyrrolidone) K90 (PVP) cross-linked with various concentrations (0, 0.125, 0.25 and 0.5%) of glutaraldehyde were evaluated as a hydrogel filler for the local delivery of lidocaine after tooth extraction. The drug-release kinetics, swellability, cytotoxicity and wound healing after tooth extraction of these non-cross-linked and cross-linked PEI–PVP hydrogels were examined in male beagles and compared to values using Spongostan®. Results demonstrated that the extent of cross-linking influenced the swelling of the resulting hydrogel, but the drug-release rates were similar. No significant changes were observed in gingival fibroblasts in contact with the PEI– PVP hydrogels or Spongostan®. In the in vivo study, PEI–PVP hydrogels showed good retention in the socket for 2 days and showed comparable wound-healing rates within 2 weeks with those of Spongostan®. In conclusion, PEI–PVP hydrogels are suitable for use as socket-dressing materials, and the release of local anaesthesia from PEI–PVP hydrogels can be sustained for a desirable period of time to prevent pain after a tooth extraction.  相似文献   

13.
A family of injectable, biodegradable and thermosensitive co-polymer nanoparticle (NP) hydrogels based on mPEG-b-POA-b-mPEG, which was synthesized from mono-methoxy poly(ethylene glycol) (mPEG) and poly(octadecanedioic anhydride) (POA), was investigated in this paper. It was found that the aqueous dispersions of these NPs underwent a reversible gel-sol transition upon temperature change. By using paclitaxel and Bovine serum albumin (BSA) as model drugs, we noticed that the in vitro releases of both in situ gel-forming formulations were sustained and no initial burst releases were observed for 7 days. In vitro cytotoxicity tests via MTT assay indicate that mPEG-b-POA-b-mPEG NPs are non-toxic to normal mouse lung fibroblast cells (L929). The in vivo hydrogel formation and in vivo biocompatibility of co-polymer NP hydrogel were also investigated and the results further validate the biocompatible nature of co-polymer NP hydrogel. In conclusion, our mPEG-b-POA-b-mPEG NP hydrogel is able to control the release of incorporated drug for longer duration.  相似文献   

14.
Diabetic patients are more susceptible to the development of chronic wounds than non-diabetics. The impaired healing properties of these wounds, which often develop debilitating bacterial infections, significantly increase the rate of lower extremity amputation in diabetic patients. We hypothesize that bacterial biofilms, or sessile communities of bacteria that reside in a complex matrix of exopolymeric material, contribute to the severity of diabetic wounds. To test this hypothesis, we developed an in vivo chronic wound, diabetic mouse model to determine the ability of the opportunistic pathogen, Pseudomonas aeruginosa, to cause biofilm-associated infections. Utilizing this model, we observed that diabetic mice with P. aeruginosa-infected chronic wounds displayed impaired bacterial clearing and wound closure in comparison with their non-diabetic littermates. While treating diabetic mice with insulin improved their overall health, it did not restore their ability to resolve P. aeruginosa wound infections or speed healing. In fact, the prevalence of biofilms and the tolerance of P. aeruginosa to gentamicin treatment increased when diabetic mice were treated with insulin. Insulin treatment was observed to directly affect the ability of P. aeruginosa to form biofilms in vitro. These data demonstrate that the chronically wounded diabetic mouse appears to be a useful model to study wound healing and biofilm infection dynamics, and suggest that the diabetic wound environment may promote the formation of biofilms. Further, this model provides for the elucidation of mechanistic factors, such as the ability of insulin to influence antimicrobial effectiveness, which may be relevant to the formation of biofilms in diabetic wounds.  相似文献   

15.
Biomaterials that actively promote both wound healing and angiogenesis are of critical importance for many biomedical applications, including tissue engineering. In particular, hyaluronic acid (HA) is an important player that has multiple roles throughout the angiogenic process in the body. Previously, our laboratory has developed photocrosslinkable HA-based scaffolds that promote angiogenesis when implanted in vivo. This paper reports the incorporation of a photocrosslinkable fibronectin (FN) conjugate into three-dimensional (3-D) HA hydrogel networks to enhance endothelial cell adhesion and angiogenesis. The results demonstrate significantly better retention of FN that was photocrosslinked within HA hydrogels compared to FN that was physically adsorbed within HA hydrogels. Increased viability of endothelial cells cultured in 3-D HA hydrogels with photoimmobilized FN, compared to adsorbed FN, was also observed. Endothelial cells were cultured within hydrogels for up to 6 days, a period over which cell proliferation, migration and an angiogenic phenotype were influenced by varying the concentration of incorporated FN. The results demonstrate the potential of these composite hydrogels as biomaterial scaffolds capable of promoting wound healing and angiogenesis.  相似文献   

16.
Ag‐nanoparticle‐containing hydrogels were successfully prepared by in situ reduction of silver nitrate in the presence of citrate molecules as stabilizing agent during photoinduced copolymerization of AAm and BAAm. Swelling‐deswelling behavior and thermal properties of the synthesized hydrogels were investigated. The interior morphology of the gels exhibit continuity, which is a common feature for hydrogel networks. Antimicrobial activities of the hydrogels were also investigated against pathogenic E. coli O157:H7, S. aureus, and non‐pathogenic E. coli K‐12, which are model microorganisms for testing bactericidal properties. The hydrogels containing well‐dispersed Ag NPs showed significant antibacterial activity.

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17.
Nanometals (NM) frequently possess potent antimicrobial potentials to combat various pathogens, but their elevated biotoxicity limits their direct applications. The biosynthesis of NM and their capping/conjugation with natural biopolymers can effectually enhance NM stability and diminish such toxicity. Yeast β-glucan (βG), from Saccharomyces cerevisiae, was extracted and transformed to nanoparticles (NPs) using alkali/acid facile protocol. The βG NPs were innovatively employed for direct biosynthesis of silver nanoparticles (Ag NPs) without extra chemical processes. The physicochemical assessments (Fourier-transform infrared, X-ray diffraction, and transmission electron microscopy) validated NPs formation, interaction, and interior capping of Ag NPs in βG NPs. The synthesized βG NPs, Ag NPs, and βG–Ag NPs composite were negatively charged and had minute particle sizes with mean diameters of 58.65, 6.72, and 63.88 nm, respectively. The NPs (plain Ag NPs and composited βG–Ag NPs) exhibited potent comparable bactericidal actions, opposing Gram+ (Staphylococcus aureus) and Gram (Escherichia coli, Salmonella Typhimurium, and Pseudomonas aeruginosa). Scanning micrographs, of treated S. aureus and S. Typhimurium with βG–Ag NPs, elucidated the powerful bactericidal actions of nanocomposite for destructing pathogens' cells. The inventive Ag NPs biosynthesis with βG NPs and the combined βG–Ag NPs nanocomposites could be impressively recommended as powerful antibacterial candidates with minor potential toxicity.  相似文献   

18.
Non-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle. GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell differentiation and produced significant enhancements in bone repair within a critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER functionalization was crucial to the BMP-2-dependent healing response. Importantly, these engineered hydrogels outperformed the current clinical carrier in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels provided sustained in vivo release of encapsulated BMP-2, increased osteoprogenitor localization in the defect site, enhanced bone formation and induced defect bridging and mechanically robust healing at low BMP-2 doses which stimulated almost no bone regeneration when delivered from collagen sponges. These findings demonstrate that GFOGER hydrogels promote bone regeneration in challenging defects with low delivered BMP-2 doses and represent an effective delivery vehicle for protein therapeutics with translational potential.  相似文献   

19.
In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., PEG and gelatin + PEG hydrogels) had enhanced primary granule release, yet similar tertiary granule release compared with PMNs cultured on polydimethylsiloxane or tissue culture polystyrene. PMN primary granules contain microbicidal proteins and proteases, which can potentially injure bystander cells, degrade the extracellular matrix, and promote inflammation. Here, we sought to understand the mechanism of the enhanced primary granule release from PMNs on PEG hydrogels. We found that primary granule release from PMNs on PEG hydrogels was adhesion mediated and involved Src family kinases and PI3K-γ. The addition of gelatin to PEG hydrogels did not further enhance PMN primary granule release. Using stable-isotope dimethyl labeling-based shotgun proteomics, we identified many serum proteins – including Ig gamma constant chain region proteins and alpha-1-acid glycoprotein 1 – that were absorbed/adsorbed in higher quantities on PEG hydrogels than on TCPS, and may be involved in mediating PMN primary granule release. Ultimately, this mechanistic knowledge can be used to direct inflammation and wound healing following biomaterial implantation to promote a more favorable healing response.  相似文献   

20.
With increase in isolation of multi and extensive drug resistance hospital pathogens (MDR, XDR) in burn centers of many hospitals in the world, attempt to use nanomaterials for treatment of burn-infected patients is the focus of researches all around the world. In the present investigation silver nanospheres (Ag NSs) has been synthesized by chicory seed exudates (CSE). The various parameters influencing the mechanism of Ag NSs synthesis including temperature, concentration, pH and time were studied. Greener Ag NSs were formed when the reaction conditions were altered with respect to pH, concentration of AgNO3 and incubation temperature. Finally, we evaluated antimicrobial activity of silver nanospheres biosynthesized by chicory (Cichodrium intybus) against most prevalent burn bacteria pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and fungus Fusarium solani. The UV visible spectroscopy, X-Ray diffraction (XRD), dynamic light scattering (DLS) used for primary screening of physicochemical properties. The transmission electron microscopy (TEM) images showed the Ag NSs (with globular shape) with a size less than 25 nm that they have the same size about 8 nm (more than 97% are 8 nm). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Ag NSs against the standard strains of A. baumannii, P. aeruginosa and K. pneumonia showed a relatively high inhibitory and bactericidal activity (MIC 1.56 μg/mL and MBC 3.12 μg/mL) of the nanoparticles and F. solani cultures. In antifungal tests, the lowest level of zone of inhibition was observed at a concentration of 5 μg/mL synthesized silver nanospheres with the 7% inhibition of growth. Ag NSs have high antimicrobial activity against three common burn bacteria pathogens and fungus F. solani. Therefore, Ag NSs can be used to prevent burn infection and for wound healing.  相似文献   

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