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1.
Int J Biol Macromol ; 265(Pt 2): 131062, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521307

RESUMO

This study introduces a novel wound dressing by combining nitric oxide-releasing thiolated starch nanoparticles (NO-TS NPs) with gelatin. First, starch was thiolated (TS), and then its nanoparticles were prepared (TS NPs). Subsequently, NPs were covalently bonded to sodium nitrite to obtain NO-releasing TS NPs (NO-TS-NPs) that were incorporated into gelatin sponges at various concentrations. The resulting spherical TS NPs had a mean size of 85.42 ± 5.23 nm, which rose to 100.73 ± 7.41 nm after bonding with sodium nitrite. FTIR spectroscopy confirmed S-nitrosation on the NO-TS NPs' surface, and morphology analysis showed well-interconnected pores in all sponges. With higher NO-TS NPs content, pore size, porosity, and water uptake increased, while compressive modulus and strength decreased. Composites exhibited antibacterial activity, particularly against E. coli, with enhanced efficacy at higher NPs' concentrations. In vitro release studies demonstrated Fickian diffusion, with faster NO release in sponges containing more NPs. The released NO amounts were non-toxic to fibroblasts, but samples with fewer NO-TS NPs exhibited superior cellular density, cell attachment, and collagen secretion. Considering the results, including favorable mechanical strength, release behavior, antibacterial and cellular properties, gelatin sponges loaded with 2 mg/mL of NO-TS NPs can be suitable for wound dressing applications.


Assuntos
Gelatina , Nanopartículas , Gelatina/química , Óxido Nítrico , Amido , Escherichia coli , Nitrito de Sódio , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Bandagens/microbiologia
2.
J Biomed Mater Res B Appl Biomater ; 112(3): e35396, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433653

RESUMO

Development of osteochondral tissue engineering approaches using scaffolds seeded with stem cells in association with mechanical stimulations has been recently considered as a promising technique for the repair of this tissue. In this study, an integrated and biomimetic trilayered silk fibroin (SF) scaffold containing SF nanofibers in each layer was fabricated. The osteogenesis and chondrogenesis of stem cells seeded on the fabricated scaffolds were investigated under a perfusion flow. 3-Dimethylthiazol-2,5-diphenyltetrazolium bromide assay showed that the perfusion flow significantly enhanced cell viability and proliferation. Analysis of gene expression by stem cells revealed that perfusion flow had significantly upregulated the expression of osteogenic and chondrogenic genes in the bone and cartilage layers and downregulated the hypertrophic gene expression in the intermediate layer of the scaffold. In conclusion, applying flow perfusion on the prepared integrated trilayered SF-based scaffold can support osteogenic and chondrogenic differentiation for repairing osteochondral defects.


Assuntos
Fibroínas , Animais , Coelhos , Fibroínas/farmacologia , Perfusão , Adipócitos , Bioensaio , Células-Tronco
3.
Int J Biol Macromol ; 251: 126173, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37558027

RESUMO

This research aims to introduce a new wound dressing with antibacterial and anti-inflammatory properties made from chitosan and copper-containing Janus nanoparticles (JNPs). The JNPs were synthesized by attaching copper to PDA nanospheres, which were then embedded in Chitosan at different concentrations. The resulting spherical JNPs had a mean size of 208 ± 96 nm, and EDX mapping showed successful adhesion of Cu2+ ions to PDA nanospheres with a total Cu2+ content of 16.5 wt%. The samples exhibited interconnected porous structures, increasing JNPs concentration resulting in larger pore size and higher porosity. The addition of JNPs to 10 % (Ch-JNP 10) resulted in the highest strength, young modulus, and crystallinity, while a reverse trend was observed at higher JNPs content. JNPs improve the antibacterial activity of chitosan-based dressing, especially against E. coli. All samples were biocompatible and did not exhibit any cytotoxic effects. Ch-JNP10 had higher cellular density, confluency, and collagen secretion than other samples. The in vivo study demonstrated that Ch-JNP10 induced epithelialization and oriented collagen fiber formation while reducing inflammation. Overall, Ch-JNP10 may be a potential wound dressing for chronic wounds.

4.
Carbohydr Polym ; 302: 120371, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36604050

RESUMO

This study aimed to develop and characterize a novel antibacterial, self-healing hydrogel made from aldehyde-carrageenan. Thus, carrageenan (CA) was first oxidized using different amounts of sodium periodate (NaIO4), and the highest concentration of aldehyde was obtained when the ratio of NaIO4 to CA was 1.5:1. Using dopamine (PDA) and zinc ions (Zn2+), various hydrogels were synthesized from oxidized carrageenan (O-CA). The effects of dopamine and zinc ions on the properties of O-CA hydrogel were examined. According to Fourier Transform Infrared Spectroscopy (FTIR) studies, the hydrogel's components are linked by Schiff bases, hydrogen bonds, and ion complexes. The rheological tests confirmed that hydrogels were elastic gels, not viscous sol, and were able to recover rapidly. Adding zinc to the hydrogel reduced weight loss (38 %) and provided extra antibacterial properties, particularly against E. coli. In addition, collagen secretion and cell attachment to Zn-containing hydrogels were significantly increased, and fibroblast viability reached 118 %. Overall, a hybrid O-CA/PDA/Zn hydrogel has excellent potential for wound healing applications.


Assuntos
Escherichia coli , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/química , Carragenina/química , Aldeídos/farmacologia , Dopamina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização , Zinco/farmacologia
5.
Int J Biol Macromol ; 216: 605-617, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35809673

RESUMO

Pectin has recently attracted increasing attention as an alternative biomaterial commonly used in biomedical and pharmaceutical fields. It shows several promising properties, including good biocompatibility, health benefits, nontoxicity, and biodegradation. In this research, novel nanocomposite fibers composed of folic acid-decorated carbon dots (CDs) in pectin/PEO matrix were fabricated using the electrospinning technique, which was never reported previously. Nitrogen-doped and nitrogen, sulfur-doped CDs were synthesized with average diameters of 2.74 nm and 2.17 nm using the one-step hydrothermal method, studied regarding their physicochemical, optical, and biocompatibility properties. The relative Quantum yields of N-CDs and N, S doped CDs were measured to be 54.7 % and 30.2 %, respectively. Nanocomposite fibers containing CDs were prepared, and their morphology, physicochemical properties, conductivity, drug release behavior, and cell viability were characterized. The results indicated that CDs improve fibrous scaffolds' tensile strength from 13.74 to 35.22 MPa while maintaining comparable extensibility. Furthermore, by incorporation of CDs in the prepared fibers conductivity enhanced from 8.69 × 10-9 S·m-1 to 1.36 × 10-4 S·m-1. The nanocomposite fibrous scaffold was also biocompatible with controlled drug release over 212 h, potentially promising tissue regeneration.


Assuntos
Nanocompostos , Pontos Quânticos , Carbono/química , Corantes Fluorescentes/química , Ácido Fólico , Nitrogênio/química , Pectinas , Pontos Quânticos/química
6.
Int J Biol Macromol ; 206: 861-874, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35314263

RESUMO

Three dimensional (3D) substrates based on natural and synthetic polymers enhance the osteogenic and mechanical properties of the bone tissue engineering scaffolds. Here, a novel bioactive composite scaffolds from polycaprolactone /kappa-carrageenan were developed for bone regeneration applications. 3D PCL scaffolds were fabricated by 3D printing method followed by coating with carboxymethyl kappa-carrageenan. This organic film was used to create calcium and strontium phosphate layers via a modified alternate soaking process in CaCl 2 /SrCl 2 and Na2HPO4 solutions in which calcium ions were replaced by strontium, with different amounts of strontium in the solutions. Various characterization techniques were executed to analyze the effects of strontium ion on the scaffold properties. The morphological results demonstrated the highly porous with interconnected pores and uniform pore sizes scaffolds. It was indicated that the highest crystallinity and compressive strength were obtained when 100% CaCl2 was replaced by SrCl2 in the solution (P-C-Sr). Incorporation of Sr onto the structure increased the degradation rate of the scaffolds. Mesenchymal stem cells (MSCs) culture on the scaffolds showed that Sr effectively improved attachment and viability of the MSCs and accelerated osteogenic differentiation as revealed by Alkaline phosphatase activity, calcium content and Real Time-Reverse transcription polymerase chain reaction assays.


Assuntos
Cálcio , Osteogênese , Adsorção , Regeneração Óssea , Cálcio/farmacologia , Fosfatos de Cálcio/farmacologia , Carragenina/farmacologia , Fosfatos , Poliésteres , Impressão Tridimensional , Estrôncio/química , Engenharia Tecidual , Tecidos Suporte/química
7.
Int J Pharm ; 610: 121227, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34699950

RESUMO

Burns is a critical fatal event due to the risk of infection and complex inflammatory cascades. This study aimed to fabricate and characterize a new antibacterial and anti-inflammatory dressing for second-degree burns by the immobilization of bromelain and zinc oxide nanoparticles on silk fibroin nanofibers. Thus, electrospun silk nanofibers with an average fiber diameter of 345 nm were prepared and then grafted with acrylic acid after exposure to O2 plasma. Next, bromelain was immobilized on the modified SF nanofibers (SF-Br). Subsequently, different amounts of ZnO NPs coated with polydopamine were immobilized on the SF-Br nanofibers. The successful immobilization of bromelain and ZnO NPs on the SF nanofibers was proved by SEM, EDS, and FTIR analysis. The loading efficiency of bromelain was 85.63%, and activity ranged between 88% and 92%. The crystallinity of SF nanofibers decreased after the addition of bromelain and ZnO NPs, which increased the bromelain and zinc ions released from the dressing. Antibacterial activity has improved with the addition of ZnO NPs. The amounts of bromelain released from the dressings are not toxic to fibroblasts. Moreover, fibroblast attachment and proliferation enhanced at lower ZnO amounts, while there was an inverse trend at high doses of ZnO NPs. In vivo studies showed that treating the burn with silk fibroin-bromelain-ZnO NPs enhanced the healing process and considerably lowered the inflammatory response at the wound. Overall, the dressing presented here offers excellent potential for burn management.


Assuntos
Queimaduras , Fibroínas , Nanofibras , Nanopartículas , Óxido de Zinco , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Bandagens , Bromelaínas , Queimaduras/tratamento farmacológico , Humanos , Seda
8.
Biomed Mater ; 16(2): 025009, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33434897

RESUMO

Core-sheath nanofibrous scaffolds from polyvinyl alcohol (PVA)-strontium ranelate (SrR)-Polycaprolactone (PCL) were prepared by water in oil electrospinning method. Thus, PCL (the oil phase) was used as the shell part and a mixture of PVA and SrR (the water phase) was inserted in the core. The amounts of SrR was varied from 0 to 15 wt.% Mussel-inspired dopamine-gelatin coating was done on the nanofibrous to improve their hydrophilicity and cellular attachment. The effect of the SrR content on morphology, mechanical, physicochemical, in vitro release behaviors, and biological properties as well as in vivo bone regeneration was investigated. Morphological observations revealed that continuous nanofibers with a core/shell structure were successfully obtained and the fibers diameter increased as the SrR content rose. X-ray diffraction (XRD) analysis revealed that SrR was molecularly distributed in the nanofibers and increasing the amount of the SrR decreased the crystallinity of the nanofibers. Moreover, the SrR release was regulated through the mechanism of Fickian diffusion and it was assumed as fast as possible in the samples with higher SrR content. The mesenchymal stem cell culturing showed improved cell proliferation by adding SrR and accelerating the expression of ALP, Runx2, Col I, and OCN genes. Besides, the SrR-loaded nanofibers improved bone formation of calvarial defects in a rat model as revealed by in vivo investigations.


Assuntos
Regeneração Óssea , Substitutos Ósseos/química , Emulsões , Nanofibras/química , Poliésteres/química , Álcool de Polivinil/química , Tiofenos/química , Animais , Bivalves , Osso e Ossos/metabolismo , Adesão Celular , Diferenciação Celular , Proliferação de Células , Técnicas In Vitro , Masculino , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Engenharia Tecidual , Tecidos Suporte/química , Viscosidade , Água/química , Difração de Raios X
9.
Int J Biol Macromol ; 173: 351-365, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33450340

RESUMO

Pectin has been regarded as a drug carrier accelerating the healing process due to its bioactivities, abundance and lower cost of resources. However, a big challenge related to its practical application is its poor mechanical strength. In this study the modified Cu-based MOF containing Folic acid was synthesized and incorporated in the suitable pectin electrospun nanofibers which not only improved the copper ions release behavior but also made the fiber mat stronger, antibacterial and induce angiogenesis, fibroblast migration, and proliferation due to loaded copper ions and folic acid. The nanofibers composing of 75% pectin and 4000 kDa -PEO were chosen after morphological and mechanical characterization. Finally, the effect of MOF incorporation on the nanocomposite samples was characterized in terms of morphological, physiochemical and biological properties. The nanofibrous mats were evaluated by tensile testing, antibacterial and cytotoxicity. The release behavior of copper ions and folic acid was controlled and their burst release alleviated reducing cytotoxicity in vitro. It was found that the Young's moduli of the pectin nanofibers were improved to 19.13 MPa by the addition of Cu-based MOFs. Moreover, nanocomposite pectin nanofibers were found to be antibacterial and biocompatible. These results demonstrate that MOF-contained pectin nanofibers are promising for biomedical applications.


Assuntos
Antibacterianos/farmacologia , Cobre/farmacologia , Ácido Fólico/farmacologia , Estruturas Metalorgânicas/farmacologia , Pectinas/química , Animais , Antibacterianos/química , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citrus/química , Cobre/química , Sistemas de Liberação de Medicamentos , Módulo de Elasticidade , Escherichia coli/efeitos dos fármacos , Ácido Fólico/química , Estruturas Metalorgânicas/química , Camundongos , Nanocompostos , Nanofibras , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos
10.
Acta Biomater ; 113: 144-163, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590170

RESUMO

Abnormal wound healing caused by the over-expression of collagen and fibronectin leads to fibrosis, the major complication of all treatment modalities. A three-layer nanofiber scaffold was designed, optimized, and fabricated. This scaffold comprised two supportive polycaprolactone (PCL)-chitosan layers on the sides and a polyvinyl alcohol (PVA)-metformin hydrochloride (metformin-HCl) in the middle. The physico-chemical properties of scaffold, such as mechanical characteristics, degradation, swelling, and in-vitro drug release, were evaluated. The biological tests, including cell viability in response to metformin-HCl and Tween 80, scaffold biocompatibility, cell attachment, and antibacterial activity, were further conducted. The wound healing effect of scaffold loaded with metformin-HCl (MSc+Met) was assessed in donut-shaped silicone splints in rats. Histopathological and immunohistochemical evaluation as well as mRNA expression levels of fibrosis markers were also studied. SEM images indicated a uniform, bead-less morphology and high porosity. Surface modification of scaffold by Tween 80 improved the surface hydrophilicity and enhanced the adhesion and proliferation of fibroblasts. The scar area on day 15 in MSc+Met was significantly lower than that of other groups. Histopathological and immunohistochemical evaluation revealed that group MSc+Met was the best, having significantly lower inflammation, higher angiogenesis, the smallest scar width and depth, maximum epitheliogenesis score, and the most optimal modulation of collagen density. Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-ß1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (α-SMA). Inhibiting these genes alleviates scar formation but delays wound healing; thus, an engineered scaffold was used to prevent delay in wound healing. These results provided evidence for the first time to introduce an anti-fibrogenic slow-releasing scaffold, which acts in a dual role, both alleviating fibrosis and accelerating wound healing.


Assuntos
Preparações de Ação Retardada , Hipoglicemiantes , Metformina , Nanofibras , Animais , Colágeno , Preparações de Ação Retardada/farmacologia , Hipoglicemiantes/administração & dosagem , Metformina/farmacologia , Ratos , Tecidos Suporte , Cicatrização
11.
Int J Biol Macromol ; 153: 317-326, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32126204

RESUMO

Among naturally occurring polymers, silk fibroin and sericin have attracted much attention in the field of tissue engineering; however, clinical application of silk fibroin/sericin scaffolds in a combined form has been questioned due to the possible pro-inflammatory reaction against native silk and fibroin/sericin 3D constructs. The objective of this study was to fabricate 3D spongy fibroin/sericin scaffolds and to explore the structural, biological and immunological properties of different ratios of fibroin and sericin. Structural characterization revealed a highly porous structure (>91%) with a large surface area and water uptake capacity for all different fibroin/sericin scaffolds. Notably, the scaffolds showed enhanced mechanical properties and a higher degradation rate with increasing sericin content. Excellent cell attachment and no significant cytotoxicity were observed in all scaffold types 7 days after seeding of osteoblast-like MG63 cells. Gene expression of pro-inflammatory markers TNF-α, CXCL10 and CD197 as well as TNF-α secretion by THP-1-derived macrophages revealed no significant immune response to all fibroin/sericin scaffold types when compared to sericin-free F1:S0 samples and a TCP (Mɸ) control group. These results demonstrate that spongy fibroin/sericin scaffolds are able to support the growth of osteoblast-like cells without eliciting a pro-inflammatory response, thus being a promising material for bone tissue engineering.


Assuntos
Fibroínas/química , Fibroínas/farmacologia , Sericinas/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Liofilização , Humanos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Fenômenos Mecânicos , Porosidade , Relação Estrutura-Atividade
12.
Colloids Surf B Biointerfaces ; 190: 110944, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32155456

RESUMO

Among strontium-based drugs, the Strontium ranelate (SrR) is a divalent strontium salt of ranelic acid which has an overall effect over the bone microarchitecture improvement. However, some findings reveal that the SrR affects in an opposite manner to the cell proliferation and osteoblastic differentiation, based on its concentration. Consequently, its release should be controlled. The incorporation of Halloysite nanotubes (HNT) as nanocarriers of SrR, into gelatine (GN) coatings, tailors the release of this anabolic bone-forming and anti-catabolic agent to stimulate bone growth. In fact, as-prepared GN/HNT-SrR coatings release 100 % SrR in phosphate buffered saline (PBS) within 21 days, and cellular studies of the nanocomposite coatings (MTT, Alkaline Phosphatase activity (ALP) and Calcium deposition assay) confirm the valuable bio-performance of these composite coatings to enhanced bone regeneration. In the present manuscript, suspensions with HNT/GN weight ratio of 0.5 are formulated to coat AISI 316 L stainless steel foils by Electrophoretic Deposition (EPD). Zeta potential determination is used to stablish the drug loading (HNT-SrR) by electrostatic interaction, as well as to optimize the dispersion of bare HNT and HNT SrR-loaded in a GN aqueous solution. Polyethilenimnine (PEI) is used as stabilizer to buffer the suspension media, assure cargo-drug dispersion and sequential release, while the thermal gelling of the suspension controls and step up the coating formation during EPD.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Argila/química , Sistemas de Liberação de Medicamentos , Gelatina/química , Nanopartículas/química , Tiofenos/farmacologia , Biomarcadores/análise , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Eletroforese , Humanos , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Tiofenos/química
13.
Biomater Sci ; 8(1): 517, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755488

RESUMO

Correction for 'Silk based scaffolds with immunomodulatory capacity: anti-inflammatory effects of nicotinic acid' by Abdollah Zakeri Siavashani et al., Biomater. Sci., 2019, DOI: 10.1039/c9bm00814d.

14.
Int J Biol Macromol ; 147: 1239-1247, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739046

RESUMO

This study offers a new antibacterial wound dressing from carboxymethyl cellulose (CMC)-human hair keratin with topical clindamycin delivery. Keratin was successfully extracted from human hair. Different sponges fabricated by changing CMC to keratin ratio were characterized and compared. Halloysite nanotubes were used as carriers to control the clindamycin release. Various characterization techniques were used to determine the effects of keratin addition on the structure, morphology, physical properties, drug release, antibacterial activity, and cellular behavior of CMC hydrogels. As proved by SEM and EDS, porous structure with interconnected pores was successfully formed and clindamycin-loaded HNTs were uniformly dispersed within the porous structures. Increasing the keratin in CMC hydrogel not only lowered its water vapor transmission rate to a suitable range for wound healing but also improved the water stability of CMC hydrogel. The in vitro release study indicated that clindamycin was released slower in samples containing higher keratin and the Fickian diffusion mechanism controlled their release profile. The fabricated dressing effectively inhibits S. aureus bacterial colonies growth after 24 h. Fibroblast culturing on the fabricated sponges indicated that cellular attachment, proliferation, and spreading were significantly enhanced with increasing the keratin amount.


Assuntos
Bandagens , Carboximetilcelulose Sódica/química , Clindamicina/administração & dosagem , Hidrogéis/química , Queratinas Específicas do Cabelo/química , Nanocompostos/química , Cicatrização/efeitos dos fármacos , Adsorção , Animais , Antibacterianos/administração & dosagem , Proliferação de Células , Celulose/química , Força Compressiva , Liberação Controlada de Fármacos , Fibroblastos/metabolismo , Cabelo/química , Humanos , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Biomater Sci ; 8(1): 148-162, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31663545

RESUMO

Implantation of temporary and permanent biomaterials in the body leads to a foreign body reaction (FBR), which may adversely affect tissue repair processes and functional integration of the biomaterial. However, modulation of the inflammatory response towards biomaterials can potentially enable a favorable healing response associated with functional tissue formation and tissue regeneration. In this work, incorporation of nicotinic acid in 3D silk scaffolds is explored as an immunomodulatory strategy for implantable biomaterials. Silk scaffolds were fabricated from dissolved Bombyx mori silk fibers by freeze-drying, resulting in silk scaffolds with high porosity (>94%), well-connected macropores, a high swelling degree (>550%) and resistance to in vitro degradation. Furthermore, drug-loaded scaffolds displayed a sustained drug release and excellent cytocompatibility could be observed with osteoblast-like MG63 cells. Cultivating M1-like macrophages on the scaffolds revealed that scaffolds loaded with nicotinic acid suppress gene expression of pro-inflammatory markers TNF-α, CXCL10 and CD197 as well as secretion of TNF-α in a concentration dependant manner. Hence, this study provides insights into the possible application of nicotinic acid in tissue engineering to control inflammatory responses towards biomaterials and potentially help minimizing FBR.


Assuntos
Anti-Inflamatórios/farmacologia , Bombyx/metabolismo , Citocinas/genética , Macrófagos/efeitos dos fármacos , Niacina/farmacologia , Seda/química , Animais , Anti-Inflamatórios/química , Proteínas de Artrópodes/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada , Regulação para Baixo , Humanos , Macrófagos/citologia , Macrófagos/imunologia , Teste de Materiais , Niacina/química , Porosidade , Engenharia Tecidual , Tecidos Suporte/química
16.
Acta Biomater ; 100: 142-157, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31586728

RESUMO

To improve the efficacy of transdermal drug delivery systems, the physical and chemical properties of drugs need to be optimized to better penetrate into the stratum corneum and to better diffuse into the epidermis and dermis layers. Accordingly, dual-biological function ionic liquids composed of active pharmaceutical ingredients were synthesized, comprising both analgesic and anti-inflammatory properties, by combining a cation derived from lidocaine and anions derived from hydrophobic nonsteroidal anti-inflammatory drugs. Active pharmaceutical ingredient ionic liquids (API-ILs) were characterized through nuclear magnetic resonance, cytotoxicity assay, and water solubility assay. All properties were compared with those of the original drugs. By converting the analgesic and anti-inflammatory drugs into dual-function API-ILs, their water solubility increased up to 470-fold, without affecting their cytotoxic profile. These API-ILs were incorporated into a bilayer wound dressing composed of a hydrophobic polyvinylidene fluoride (PVDF) membrane to act as a drug reservoir and a biocompatible hyaluronic acid (HA) layer. The prepared bilayer wound dressing was characterized in terms of mechanical properties, membrane drug uptake and drug release behavior, and application in transdermal delivery, demonstrating to have desirable mechanical properties and improved release of API-ILs. The assessment of anti-inflammatory activity through the inhibition of LPS-induced production of nitric oxide and prostaglandin E2 by macrophages revealed that the prepared membranes containing API-ILs are as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assay confirmed improved the viability and adhesion of fibroblasts on PVDF/HA membranes. Finally, wound healing assay performed with fibroblasts showed that the bilayer membranes containing dual-function API-ILs are not detrimental to wound healing, while displaying increased and controlled drug delivery and dual therapeutic behavior. STATEMENT OF SIGNIFICANCE: This work shows the preparation and characterization of bilayer wound dressings comprising dual-biological function active pharmaceutical ingredients based on ionic liquids with improved and controlled drug release and dual therapeutic efficiency. By converting analgesic and anti-inflammatory drugs into ionic liquids, their water solubility increases up to 470-fold. The prepared bilayer wound dressing membranes have desirable mechanical properties and improved release of drugs. The prepared membranes comprising ionic liquids display anti-inflammatory activity as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assays show improved viability and adhesion of fibroblasts on PVDF/HA membranes, being thus of high relevance as effective transdermal drug delivery systems.


Assuntos
Bandagens , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Líquidos Iônicos/química , Polivinil/química , Cicatrização/efeitos dos fármacos , Células 3T3 , Animais , Anti-Inflamatórios/farmacologia , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Módulo de Elasticidade , Camundongos , Células RAW 264.7 , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Resistência à Tração , Água/química
17.
Int J Biol Macromol ; 140: 278-287, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400428

RESUMO

Conductive scaffolds are suitable candidates for cardiovascular tissue engineering (CTE) due to their similarity to the extracellular matrix of native tissue. Here, nanofiber scaffolds based on polyvinyl alcohol (PVA), chitosan (CS), and different concentrations of carbon nanotube (CNT) were produced using electrospinning. Scanning electron microscopy (SEM) image, mechanical test (elastic modulus: 130 ±â€¯3.605 MPa), electrical conductivity (3.4 × 10-6 S/Cm), water uptake, cell adhesion, and cell viability (>80%) results of the PVA-CS-CNT1 scaffold revealed that the nanofiber containing 1% of CNT has optimal properties for cardiac differentiation. Afterwards, the differentiation of rat mesenchymal stem cells (MSCs) to cardiomyocytes was performed on the optimal scaffold by electrical stimulation in the presence of 5-azacytidine, TGF-ß and ascorbic acid. The real-time qPCR results indicated that the expression of Nkx2.5, Troponin I, and ß-MHC cardiac marker was increased significantly (>3 folds) in comparison to control group. Based on the findings of this study, the incorporation of MSCs, conductive scaffolds, and electrical stimulation seem to be a promising approach in CTE.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Nanofibras/química , Nanotubos de Carbono/química , Álcool de Polivinil/química , Engenharia Tecidual , Tecidos Suporte , Animais , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Módulo de Elasticidade , Condutividade Elétrica , Masculino , Células-Tronco Mesenquimais/fisiologia , Miócitos Cardíacos/fisiologia , Ratos
18.
Carbohydr Polym ; 222: 115033, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320054

RESUMO

Hyaluronic acid (HA), a naturally sourced polysaccharide, has shown remarkable effectiveness on wound healing, but its low mechanical strength and instability limits its frequent application in this field. In order to minimize this shortcoming, hyaluronic acid based wound dressings were blended with functionalized ZIF-8, which not only provides high mechanical strength, but also introduces antibacterial properties and promotes fibroblast migration and proliferation. To analyze physiochemical and biological characteristics of prepared wound dressings, tests including DLS, XRD, FTIR as well as antibacterial and cell adhesion assays were carried out. Results indicated that HA film modification boosted the Young's modulus from 138 to 176 K Pa, and reduced the water contact angle from 37.4 to 27.7 proving enhancement in hydrophilicity. Ameliorated antibacterial properties and better cell adhesion were also observed. Suitable cell viability was observed in samples with FZIF-8, since released Zn ions maintained within a safe concentration range.


Assuntos
Antibacterianos/farmacologia , Ácido Hialurônico/farmacologia , Estruturas Metalorgânicas/farmacologia , Animais , Antibacterianos/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Módulo de Elasticidade , Escherichia coli/efeitos dos fármacos , Ácido Hialurônico/química , Imidazóis/química , Estruturas Metalorgânicas/química , Camundongos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Resistência à Tração , Zinco/química
19.
Mater Sci Eng C Mater Biol Appl ; 100: 874-885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948125

RESUMO

In order to prepare bone tissue engineered scaffolds, zein, a natural polymer isolated from corn, was used as a starting material. Zein provides ideal properties for tissue engineered scaffolds, and the products derived from its degradation are non-toxic. To enhance the osteogenic properties of the scaffold, hydroxyapatite mineral was used in the form of nanospheres. Hydroxyapatite nanoparticles are designed to carry a drug in addition to the role they play in bone tissue engineering. The surface of the hydroxyapatite nanoparticles was modified with negatively charged poly (sodium 4-styrene sulfonate) polymer, and their surface was then loaded with positively charged Vancomycin as a model drug. The scaffolds were evaluated by structural and cellular assays. FTIR and particle zeta potential tests confirmed the presence of PSS and Vancomycin in nanoparticles. The results showed a decrease in the porosity of the scaffolds and a reduction of scaffold degradation over an eight week period by increasing the concentration of hydroxyapatite nanoparticles, compared to the pure zein sample. It was observed that increasing the concentration of nanoparticles to an optimum concentration can improve the mechanical properties of scaffolds. The drug release from the scaffolds over two weeks was increased with an increase in hydroxyapatite concentration, and cell viability assays showed >90% viability of cells in scaffolds containing hydroxyapatite nanoparticles, which were confirmed to be accumulating in a proper fashion according to cell adhesion assays.


Assuntos
Portadores de Fármacos/química , Durapatita/química , Nanopartículas/química , Poliestirenos/química , Tecidos Suporte/química , Vancomicina/farmacologia , Zeína/química , Linhagem Celular Tumoral , Força Compressiva , Liberação Controlada de Fármacos , Módulo de Elasticidade , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/ultraestrutura , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Propriedades de Superfície , Viscosidade , Água/química
20.
Int J Biol Macromol ; 133: 795-803, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31028813

RESUMO

The purpose of this study was to investigate physical, mechanical, and osteogenic properties of silk fibroin (SF) nanofibers containing Urtica dioica L. (nettle) extract at different concentrations. In this respect, the successful incorporation of nettle in SF nanofibers was analyzed and then confirmed through Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The mean fiber diameter, water uptake, breaking strain, cellular attachment, and proliferation of the given nanofibers also increased as the nettle content was added, while this trend was opposite in terms of tensile strength and modulus. The in vitro release studies correspondingly demonstrated that the nettle release had been controlled according to Fickian diffusion and it was faster in the samples including more nettle. Furthermore, both ARS staining and real-time RT-PCR results suggested that nettle had enhanced the expression of both early and late markers of osteoblast differentiation in a dose-dependent manner.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fibroínas/química , Nanofibras/química , Osteogênese/efeitos dos fármacos , Urtica dioica/química , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fenômenos Mecânicos , Osteocalcina/metabolismo
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