Sustained release of antibiotics from injectable and thermally responsive polypeptide depots.

Science.gov (United States)

Adams, Samuel B; Shamji, Mohammed F; Nettles, Dana L; Hwang, Priscilla; Setton, Lori A

2009-07-01

Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to undergo in situ depot formation at body temperature. ELPs were modified to enable loading with the antibiotics, cefazolin, and vancomycin, followed by induction of the phase transition in vitro. Cefazolin and vancomycin concentrations were monitored, as well as bioactivity of the released antibiotics, to test an ability of the ELP depot to provide for prolonged release of bioactive drugs. Further tests of formulation viscosity were conducted to test suitability as an injectable drug carrier. Results demonstrate sustained release of therapeutic concentrations of bioactive antibiotics by the ELP, with first-order time constants for drug release of approximately 25 h for cefazolin and approximately 500 h for vancomycin. These findings illustrate that an injectable, in situ forming ELP depot can provide for sustained release of antibiotics with an effect that varies across antibiotic formulation. ELPs have important advantages for drug delivery, as they are known to be biocompatible, biodegradable, and elicit no known immune response. These benefits suggest distinct advantages over currently used carriers for antibiotic drug delivery in orthopedic applications. (c) 2008 Wiley Periodicals, Inc.

Tough and flexible CNT-polymeric hybrid scaffolds for engineering cardiac constructs.

Science.gov (United States)

Kharaziha, Mahshid; Shin, Su Ryon; Nikkhah, Mehdi; Topkaya, Seda Nur; Masoumi, Nafiseh; Annabi, Nasim; Dokmeci, Mehmet R; Khademhosseini, Ali

2014-08-01

In the past few years, a considerable amount of effort has been devoted toward the development of biomimetic scaffolds for cardiac tissue engineering. However, most of the previous scaffolds have been electrically insulating or lacked the structural and mechanical robustness to engineer cardiac tissue constructs with suitable electrophysiological functions. Here, we developed tough and flexible hybrid scaffolds with enhanced electrical properties composed of carbon nanotubes (CNTs) embedded aligned poly(glycerol sebacate):gelatin (PG) electrospun nanofibers. Incorporation of varying concentrations of CNTs from 0 to 1.5% within the PG nanofibrous scaffolds (CNT-PG scaffolds) notably enhanced fiber alignment and improved the electrical conductivity and toughness of the scaffolds while maintaining the viability, retention, alignment, and contractile activities of cardiomyocytes (CMs) seeded on the scaffolds. The resulting CNT-PG scaffolds resulted in stronger spontaneous and synchronous beating behavior (3.5-fold lower excitation threshold and 2.8-fold higher maximum capture rate) compared to those cultured on PG scaffold. Overall, our findings demonstrated that aligned CNT-PG scaffold exhibited superior mechanical properties with enhanced CM beating properties. It is envisioned that the proposed hybrid scaffolds can be useful for generating cardiac tissue constructs with improved organization and maturation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sustained Release of Antibiotics from Injectable and Thermally Responsive Polypeptide Depots

OpenAIRE

Adams, Samuel B.; Shamji, Mohammed F.; Nettles, Dana L.; Hwang, Priscilla; Setton, Lori A.

2009-01-01

Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to u...

Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation

Science.gov (United States)

Sleep, Eduard; McClendon, Mark T.; Preslar, Adam T.; Chen, Charlotte H.; Sangji, M. Hussain; Pérez, Charles M. Rubert; Haynes, Russell D.; Meade, Thomas J.; Blau, Helen M.; Stupp, Samuel I.

2017-01-01

Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice. PMID:28874575

Novel endotoxin-sequestering compounds with terephthalaldehyde-bis-guanylhydrazone scaffolds.

Science.gov (United States)

Khownium, Kriangsak; Wood, Stewart J; Miller, Kelly A; Balakrishna, Rajalakshmi; Nguyen, Thuan B; Kimbrell, Matthew R; Georg, Gunda I; David, Sunil A

2006-03-01

We have shown that lipopolyamines bind to the lipid A moiety of lipopolysaccharide, a constituent of Gram-negative bacterial membranes, and neutralize its toxicity in animal models of endotoxic shock. In an effort to identify non-polyamine scaffolds with similar endotoxin-recognizing features, we had observed an unusually high frequency of hits containing guanylhydrazone scaffolds in high-throughput screens. We now describe the syntheses and preliminary structure-activity relationships in a homologous series of bis-guanylhydrazone compounds decorated with hydrophobic functionalities. These first-generation compounds bind and neutralize lipopolysaccharide with a potency comparable to that of polymyxin B, a peptide antibiotic known to sequester LPS.

Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan.

Science.gov (United States)

Yang, Ying; Yang, Shengbing; Wang, Yugang; Yu, Zhifeng; Ao, Haiyong; Zhang, Hongbo; Qin, Ling; Guillaume, Olivier; Eglin, David; Richards, R Geoff; Tang, Tingting

2016-12-01

Contaminated or infected bone defects remain serious challenges in clinical trauma and orthopaedics, and a bone substitute with both osteoconductivity and antibacterial properties represents an improvement for treatment strategy. In this study, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) was grafted to 3D-printed scaffolds composed of polylactide-co-glycolide (PLGA) and hydroxyapatite (HA), in order to design bone engineering scaffolds endowed with antibacterial and osteoconductive properties. We found that both the PLGA/HA/HACC and PLGA/HACC composite scaffolds decreased bacterial adhesion and biofilm formation under in vitro and in vivo conditions. Additionally, ATP leakage assay indicated that immobilizing HACC on the scaffolds could effectively disrupt microbial membranes. Using human bone marrow-derived mesenchymal stem cells (hBMSCs), we demonstrated that HA incorporated scaffolds, including PLGA/HA and PLGA/HA/HACC, favoured cell attachment, proliferation, spreading and osteogenic differentiation compared to HA-free PLGA or PLGA/HACC scaffolds. Finally, an in vivo biocompatibility assay conducted on rats, showed that HA incorporated scaffolds (including PLGA/HA and PLGA/HA/HACC scaffolds) exhibited good neovascularization and tissue integration. Taken together, our findings support the approach for developing porous PLGA/HA/HACC composite scaffold with potential clinical application in the treatment of infected bone. Although plenty of conductive scaffold biomaterials have been exploited to improve bone regeneration under infection, potential tissue toxicity under high concentration and antibiotic-resistance are their main deficiencies. This study indicated that HACC-grafted PLGA/HA composite scaffold prepared using an innovative 3D-printing technique and covalent grafting strategy showed significantly enhanced antibacterial activities, especially against the antibiotic-resistant strains, together with good osteogenic

Characterization of Small Molecule Scaffolds that Bind to the Shigella Type III Secretion System Protein IpaD

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Dey, Supratim; Anbanandam, Asokan; Mumford, Ben E.; De Guzman, Roberto N.

2017-01-01

Many pathogens such as Shigella and other bacteria assemble the type III secretion system (T3SS) nanoinjector to inject virulence proteins into their target cells to cause infectious diseases in humans. The rise of drug resistance among pathogens that rely on the T3SS for infectivity, plus the dearth of new antibiotics require alternative strategies in developing new antibiotics. The Shigella T3SS tip protein IpaD is an attractive target for developing anti-infectives because of its essential role in virulence and its exposure on the bacterial surface. Currently, the only known small molecules that bind to IpaD are bile salts sterols. Here, we identified four new small molecule scaffolds that bind to IpaD based on the methylquinoline, pyrrolidin-aniline, hydroxyindole, and morpholinoaniline scaffolds. NMR mapping revealed potential hotspots in IpaD for binding small molecules. These scaffolds can be used as building blocks in developing small molecule inhibitors of IpaD that could lead to new anti-infectives. PMID:28750143

Advanced Scaffolds for Dental Pulp and Periodontal Regeneration.

Science.gov (United States)

Bottino, Marco C; Pankajakshan, Divya; Nör, Jacques E

2017-10-01

No current therapy promotes root canal disinfection and regeneration of the pulp-dentin complex in cases of pulp necrosis. Antibiotic pastes used to eradicate canal infection negatively affect stem cell survival. Three-dimensional easy-to-fit antibiotic-eluting nanofibers, combined with injectable scaffolds, enriched or not with stem cells and/or growth factors, may increase the likelihood of achieving predictable dental pulp regeneration. Periodontitis is an aggressive disease that impairs the integrity of tooth-supporting structures and may lead to tooth loss. The latest advances in membrane biomodification to endow needed functionalities and technologies to engineer patient-specific membranes/constructs to amplify periodontal regeneration are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Zinc Oxide Addition on Antibacterial Behavior of Hydroxyapatite-Poly lactic-co-glycolic acid Scaffold for Bone Tissue Engineering Applications

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Narges Abotalebi

2018-03-01

Full Text Available Introduction: Infection after the surgery is one of the problems of bone scaffolds implants which is normally treated by systemic administration of antibiotics. But due to the poor blood circulation in bone tissue, large antibiotic doses are needed which lead to further drawbacks to renal and hepatic systems. Material and method: In this study, the effect of zinc oxide addition on antibacterial behavior of hydroxyapatite- Poly lactic-co-glycolic acid scaffold was evaluated. The synthesized composite was characterized by X-ray diffraction, scanning electron microscopy equipped with elemental analysis and Fourier transform infrared spectra. In order to determine the antibacterial activity of the fabricated scaffold, Staphylococcus aureus (ATTC 25922 and Escherichia coli (ATTC 25923 were used as test microorganisms. Results: The results showed that Hydroxyapatite- Poly lactic-co-glycolic acid scaffold did not make inhibition zone in culture medium but the modification of Hydroxyapatite- Poly lactic-co-glycolic acid scaffold’s surface by zinc oxide particles caused Hydroxyapatite- Poly lactic-co-glycolic acid- zinc oxide scaffold to have antibacterial inhibition zone of 12 and 20 mm for Escherichia coli and Staphylococcus aureus, respectively. Discussion and conclusion: This study revealed that the addition of antibacterial agent to applicable bone tissue engineering scaffolds could be considered as an appropriate way to prevent the growth of infection at the scaffold site.

PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering.

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Esposito, Andrea Rodrigues; Moda, Marlon; Cattani, Silvia Mara de Melo; de Santana, Gracy Mara; Barbieri, Juliana Abreu; Munhoz, Monique Moron; Cardoso, Túlio Pereira; Barbo, Maria Lourdes Peris; Russo, Teresa; D'Amora, Ugo; Gloria, Antonio; Ambrosio, Luigi; Duek, Eliana Aparecida de Rezende

2013-04-01

The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration.

Genome Engineering and Modification Toward Synthetic Biology for the Production of Antibiotics.

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Zou, Xuan; Wang, Lianrong; Li, Zhiqiang; Luo, Jie; Wang, Yunfu; Deng, Zixin; Du, Shiming; Chen, Shi

2018-01-01

Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics. © 2017 Wiley Periodicals, Inc.

How important are scaffolds and their surface properties in regenerative medicine

Energy Technology Data Exchange (ETDEWEB)

Idaszek, J.; Kijeńska, E.; Łojkowski, M.; Swieszkowski, W., E-mail: wojciech.swieszkowski@inmat.pw.edu.pl

2016-12-01

Highlights: • Cell performance on AM scaffolds can be controlled by modification of surface chemistry as well as their architecture. • Introduction of chemical groups/particles increasing surface wettability and surface energy has a positive effect on cell retention and adhesion. • The properties of nanofiber scaffold like fibers orientation, wettability, roughness and chemical composition direct spreading, proliferation, maturation and differentiation of the cells promoting tissue re-growth. - Abstract: The ability of cells to sense various cues present within their natural habitat gives a tremendous opportunity to steer their fate in vitro within artificial matrices (scaffolds). However, the variety of signals and their chemical and physical origin makes engineering of the scaffolds quite challenging and requires careful design in order to obtained the desired outcome. Herein, we discuss the effect of architecture and surface of scaffolds fabricated by means of additive manufacturing and electrospinning on cell retention, spreading, proliferation and differentiation. Additionally, we present some of the reported surface and bulk modifications of the scaffolds, which positively affected cell performance. Finally, in the last part we discuss application of multicellular spheroids as a useful tool to study cell performance within three-dimensional and porous structures.

How important are scaffolds and their surface properties in regenerative medicine

International Nuclear Information System (INIS)

Idaszek, J.; Kijeńska, E.; Łojkowski, M.; Swieszkowski, W.

2016-01-01

Highlights: • Cell performance on AM scaffolds can be controlled by modification of surface chemistry as well as their architecture. • Introduction of chemical groups/particles increasing surface wettability and surface energy has a positive effect on cell retention and adhesion. • The properties of nanofiber scaffold like fibers orientation, wettability, roughness and chemical composition direct spreading, proliferation, maturation and differentiation of the cells promoting tissue re-growth. - Abstract: The ability of cells to sense various cues present within their natural habitat gives a tremendous opportunity to steer their fate in vitro within artificial matrices (scaffolds). However, the variety of signals and their chemical and physical origin makes engineering of the scaffolds quite challenging and requires careful design in order to obtained the desired outcome. Herein, we discuss the effect of architecture and surface of scaffolds fabricated by means of additive manufacturing and electrospinning on cell retention, spreading, proliferation and differentiation. Additionally, we present some of the reported surface and bulk modifications of the scaffolds, which positively affected cell performance. Finally, in the last part we discuss application of multicellular spheroids as a useful tool to study cell performance within three-dimensional and porous structures.

N-O chemistry for antibiotics: discovery of N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds as selective antibacterial agents using nitroso Diels-Alder and ene chemistry.

Science.gov (United States)

Wencewicz, Timothy A; Yang, Baiyuan; Rudloff, James R; Oliver, Allen G; Miller, Marvin J

2011-10-13

The discovery, syntheses, and structure-activity relationships (SAR) of a new family of heterocyclic antibacterial compounds based on N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds are described. A structurally diverse library of ∼100 heterocyclic molecules generated from Lewis acid-mediated nucleophilic ring-opening reactions with nitroso Diels-Alder cycloadducts and nitroso ene reactions with substituted alkenes was evaluated in whole cell antibacterial assays. Compounds containing the N-alkyl-N-(pyridin-2-yl)hydroxylamine structure demonstrated selective and potent antibacterial activity against the Gram-positive bacterium Micrococcus luteus ATCC 10240 (MIC(90) = 2.0 μM or 0.41 μg/mL) and moderate activity against other Gram-positive strains including antibiotic resistant strains of Staphylococcus aureus (MRSA) and Enterococcus faecalis (VRE). A new synthetic route to the active core was developed using palladium-catalyzed Buchwald-Hartwig amination reactions of N-alkyl-O-(4-methoxybenzyl)hydroxylamines with 2-halo-pyridines that facilitated SAR studies and revealed the simplest active structural fragment. This work shows the value of using a combination of diversity-oriented synthesis (DOS) and parallel synthesis for identifying new antibacterial scaffolds.

[Preliminary study of constructing tissue-engineered cartilage with the endoskeletal scaffold of HDPE by bone marrow stromal cells].

Science.gov (United States)

Zhu, Lie; Jiang, Hua; Zhou, Guang-Dong; Wu, Yu-Jia; Luo, Xu-Song

2008-09-01

To explore the feasibility of using a nonreactive, permanent endoskeletal scaffold to create the prothesis in special shape which is covered with tissue-engineered cartilage. Porcine BMSCs and articular chondrocytes were isolated and expanded respectively in vitro. Porcine BMSC of passage 1 in the concentration of 10 x 10(7)/ml were seeded onto a cylinder-shaped PGA (1 mm in thickness)/Medpor (3mm in diameter and 5mm in highness) scaffold as the experimental group. After the cell-scaffold constructs were cultured for 5 days, the primary medium, high-glucose DMEM medium with 10% fetal bovine serum (FBS), was replaced by chondrogenically inductive medium for 4 weeks. BMSCs and chondrocytes of the same concentration were seeded respectively onto the scaffold as the negative control group and the positive control group. After cultured in vitro for 4 weeks, the cell-scaffolds construct were implanted into subcutaneous pockets on the back of nude mice. Four and eight weeks later, the formed cartilage prosthesis were harvested and then evaluated by gross view, histology, immunohistochemistry and glycosamino-glycan (GAG) content. Cells in all groups had fine adhesion to the scaffold and could secrete extracellular matrix. All specimens in experimental group and positive control group formed mature cartilage with collagen II expression.The mature catrtilage wraped HDPE compactly and grown into the gap of HDPE. Mature lacuna structures and metachromatic matrices were also observed in these specimens. GAG contents in experimental group were (5.13 +/- 0.32) mg/g (4 weeks), (5.37 +/- 0.12) mg/g (8 weeks). In contrast, specimens in BMSC group showed mainly fibrous tissue. It indicates that it is feasible to create special shaped tissue-engineering cartilage with the permanent internal support using BMSCs as seed cell.

The Scaffold Immune Microenvironment: Biomaterial-Mediated Immune Polarization in Traumatic and Nontraumatic Applications.

Science.gov (United States)

Sadtler, Kaitlyn; Allen, Brian W; Estrellas, Kenneth; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

2017-10-01

The immune system mediates tissue growth and homeostasis and is the first responder to injury or biomaterial implantation. Recently, it has been appreciated that immune cells play a critical role in wound healing and tissue repair and should thus be considered potentially beneficial, particularly in the context of scaffolds for regenerative medicine. In this study, we present a flow cytometric analysis of cellular recruitment to tissue-derived extracellular matrix scaffolds, where we quantitatively describe the infiltration and polarization of several immune subtypes, including macrophages, dendritic cells, neutrophils, monocytes, T cells, and B cells. We define a specific scaffold-associated macrophage (SAM) that expresses CD11b + F4/80 + CD11c +/- CD206 hi CD86 + MHCII + that are characteristic of an M2-like cell (CD206 hi ) with high antigen presentation capabilities (MHCII + ). Adaptive immune cells tightly regulate the phenotype of a mature SAM. These studies provide a foundation for detailed characterization of the scaffold immune microenvironment of a given biomaterial scaffold to determine the effect of scaffold changes on immune response and subsequent therapeutic outcome of that material.

Characterization of Small-Molecule Scaffolds That Bind to the Shigella Type III Secretion System Protein IpaD.

Science.gov (United States)

Dey, Supratim; Anbanandam, Asokan; Mumford, Ben E; De Guzman, Roberto N

2017-09-21

Many pathogens such as Shigella and other bacteria assemble the type III secretion system (T3SS) nanoinjector to inject virulence proteins into their target cells to cause infectious diseases in humans. The rise of drug resistance among pathogens that rely on the T3SS for infectivity, plus the dearth of new antibiotics require alternative strategies in developing new antibiotics. The Shigella T3SS tip protein IpaD is an attractive target for developing anti-infectives because of its essential role in virulence and its exposure on the bacterial surface. Currently, the only known small molecules that bind to IpaD are bile salt sterols. In this study we identified four new small-molecule scaffolds that bind to IpaD, based on the methylquinoline, pyrrolidine-aniline, hydroxyindole, and morpholinoaniline scaffolds. NMR mapping revealed potential hotspots in IpaD for binding small molecules. These scaffolds can be used as building blocks in developing small-molecule inhibitors of IpaD that could lead to new anti-infectives. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Addition of selenium nanoparticles to electrospun silk scaffolds improves mammalian cell activity while reducing bacterial growth

Directory of Open Access Journals (Sweden)

Stanley Chung

2016-07-01

Full Text Available Silk possesses many beneficial wound healing properties, and electrospun scaffolds are especially applicable for skin applications, due to their smaller interstices and higher surface areas compared to non-electrospun equivalents. However, purified silk promotes microbial growth. In contrast, selenium nanoparticles have excellent antibacterial properties and are a novel antimicrobial chemistry. Here, electrospun silk scaffolds were doped with selenium nanoparticles to impart antibacterial properties to the silk scaffolds. Results showed significantly improved bacterial inhibition and improvement in human dermal fibroblast metabolic activity. These results suggest that the addition of selenium nanoparticles to electrospun silk is a promising approach to improve wound healing with reduced infection, without relying on antibiotics.

Graphene foam as a biocompatible scaffold for culturing human neurons

Science.gov (United States)

Mattei, Cristiana; Nasr, Babak; Hudson, Emma J.; Alshawaf, Abdullah J.; Chana, Gursharan; Everall, Ian P.; Dottori, Mirella; Skafidas, Efstratios

2018-01-01

In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation. PMID:29657752

Scaffold expulsion and genome packaging trigger stabilization of herpes simplex virus capsids

Science.gov (United States)

Roos, Wouter H.; Radtke, Kerstin; Kniesmeijer, Edward; Geertsema, Hylkje; Sodeik, Beate; Wuite, Gijs J. L.

2009-01-01

Herpes simplex virus type 1 (HSV1) capsids undergo extensive structural changes during maturation and DNA packaging. As a result, they become more stable and competent for nuclear egress. To further elucidate this stabilization process, we used biochemical and nanoindentation approaches to analyze the structural and mechanical properties of scaffold-containing (B), empty (A), and DNA-containing (C) nuclear capsids. Atomic force microscopy experiments revealed that A and C capsids were mechanically indistinguishable, indicating that the presence of DNA does not account for changes in mechanical properties during capsid maturation. Despite having the same rigidity, the scaffold-containing B capsids broke at significantly lower forces than A and C capsids. An extraction of pentons with guanidine hydrochloride (GuHCl) increased the flexibility of all capsids. Surprisingly, the breaking forces of the modified A and C capsids dropped to similar values as those of the GuHCl-treated B capsids, indicating that mechanical reinforcement occurs at the vertices. Nonetheless, it also showed that HSV1 capsids possess a remarkable structural integrity that was preserved after removal of pentons. We suggest that HSV1 capsids are stabilized after removal of the scaffold proteins, and that this stabilization is triggered by the packaging of DNA, but independent of the actual presence of DNA. PMID:19487681

Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

Directory of Open Access Journals (Sweden)

Patricia Ros-Tárraga

2016-09-01

Full Text Available This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared. The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung as a result of degradation products being released.

Electrospun conductive nanofibrous scaffolds for engineering cardiac tissue and 3D bioactuators.

Science.gov (United States)

Wang, Ling; Wu, Yaobin; Hu, Tianli; Guo, Baolin; Ma, Peter X

2017-09-01

Mimicking the nanofibrous structure similar to extracellular matrix and conductivity for electrical propagation of native myocardium would be highly beneficial for cardiac tissue engineering and cardiomyocytes-based bioactuators. Herein, we developed conductive nanofibrous sheets with electrical conductivity and nanofibrous structure composed of poly(l-lactic acid) (PLA) blending with polyaniline (PANI) for cardiac tissue engineering and cardiomyocytes-based 3D bioactuators. Incorporating of varying contents of PANI from 0wt% to 3wt% into the PLA polymer, the electrospun nanofibrous sheets showed enhanced conductivity while maintaining the same fiber diameter. These PLA/PANI conductive nanofibrous sheets exhibited good cell viability and promoting effect on differentiation of H9c2 cardiomyoblasts in terms of maturation index and fusion index. Moreover, PLA/PANI nanofibrous sheets enhanced the cell-cell interaction, maturation and spontaneous beating of primary cardiomyocytes. Furthermore, the cardiomyocytes-laden PLA/PANI conductive nanofibrous sheets can form 3D bioactuators with tubular and folding shapes, and spontaneously beat with much higher frequency and displacement than that on cardiomyocytes-laden PLA nanofibrous sheets. Therefore, these PLA/PANI conductive nanofibrous sheets with conductivity and extracellular matrix like nanostructure demonstrated promising potential in cardiac tissue engineering and cardiomyocytes-based 3D bioactuators. Cardiomyocytes-based bioactuators have been paid more attention due to their spontaneous motion by integrating cardiomyocytes into polymer structures, but developing suitable scaffolds for bioactuators remains challenging. Electrospun nanofibrous scaffolds have been widely used in cardiac tissue engineering because they can mimic the extracellular matrix of myocardium. Developing conductive nanofibrous scaffolds by electrospinning would be beneficial for cardiomyocytes-based bioactuators, but such scaffolds have been

3D printing nano conductive multi-walled carbon nanotube scaffolds for nerve regeneration

Science.gov (United States)

Lee, Se-Jun; Zhu, Wei; Nowicki, Margaret; Lee, Grace; Nyoung Heo, Dong; Kim, Junghoon; Zuo, Yi Y.; Zhang, Lijie Grace

2018-02-01

Objective. Nanomaterials, such as carbon nanotubes (CNTs), have been introduced to modify the surface properties of scaffolds, thus enhancing the interaction between the neural cells and biomaterials. In addition to superior electrical conductivity, CNTs can provide nanoscale structures similar to those present in the natural neural environment. The primary objective of this study is to investigate the proliferative capability and differential potential of neural stem cells (NSCs) seeded on a CNT incorporated scaffold. Approach. Amine functionalized multi-walled carbon nanotubes (MWCNTs) were incorporated with a PEGDA polymer to provide enhanced electrical properties as well as nanofeatures on the surface of the scaffold. A stereolithography 3D printer was employed to fabricate a well-dispersed MWCNT-hydrogel composite neural scaffold with a tunable porous structure. 3D printing allows easy fabrication of complex 3D scaffolds with extremely intricate microarchitectures and controlled porosity. Main results. Our results showed that MWCNT-incorporated scaffolds promoted neural stem cell proliferation and early neuronal differentiation when compared to those scaffolds without the MWCNTs. Furthermore, biphasic pulse stimulation with 500 µA current promoted neuronal maturity quantified through protein expression analysis by quantitative polymerase chain reaction. Significance. Results of this study demonstrated that an electroconductive MWCNT scaffold, coupled with electrical stimulation, may have a synergistic effect on promoting neurite outgrowth for therapeutic application in nerve regeneration.

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

Science.gov (United States)

Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Bioactive polymeric–ceramic hybrid 3D scaffold for application in bone tissue regeneration

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Torres, A.L.; Gaspar, V.M.; Serra, I.R.; Diogo, G.S.; Fradique, R. [CICS-UBI — Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Silva, A.P. [CAST-UBI — Centre for Aerospace Science and Technologies, University of Beira Interior, Calçada Fonte do Lameiro, 6201-001 Covilhã (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI — Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal)

2013-10-01

The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the importance of alginate incorporation in the production of improved and tunable β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) three-dimensional (3D) porous scaffolds to be used as temporary templates for bone regeneration. Different bioceramic combinations were tested in order to investigate optimal scaffold architectures. Additionally, 3D β-TCP/HA vacuum-coated with alginate, presented improved compressive strength, fracture toughness and Young's modulus, to values similar to those of native bone. The hybrid 3D polymeric–bioceramic scaffolds also supported osteoblast adhesion, maturation and proliferation, as demonstrated by fluorescence microscopy. To the best of our knowledge this is the first time that a 3D scaffold produced with this combination of biomaterials is described. Altogether, our results emphasize that this hybrid scaffold presents promising characteristics for its future application in bone regeneration. - Graphical abstract: B-TCP:HA–alginate hybrid 3D porous scaffolds for application in bone regeneration. - Highlights: • The produced hybrid 3D scaffolds are prone to be applied in bone tissue engineering. • Alginate coated 3D scaffolds present high mechanical and biological properties. • In vitro assays for evaluation of human osteoblast cell attachment in the presence of the scaffolds • The hybrid 3D scaffolds present suitable mechanical and biological properties for use in bone regenerative medicine.

Bioactive polymeric–ceramic hybrid 3D scaffold for application in bone tissue regeneration

International Nuclear Information System (INIS)

Torres, A.L.; Gaspar, V.M.; Serra, I.R.; Diogo, G.S.; Fradique, R.; Silva, A.P.; Correia, I.J.

2013-01-01

The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the importance of alginate incorporation in the production of improved and tunable β-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) three-dimensional (3D) porous scaffolds to be used as temporary templates for bone regeneration. Different bioceramic combinations were tested in order to investigate optimal scaffold architectures. Additionally, 3D β-TCP/HA vacuum-coated with alginate, presented improved compressive strength, fracture toughness and Young's modulus, to values similar to those of native bone. The hybrid 3D polymeric–bioceramic scaffolds also supported osteoblast adhesion, maturation and proliferation, as demonstrated by fluorescence microscopy. To the best of our knowledge this is the first time that a 3D scaffold produced with this combination of biomaterials is described. Altogether, our results emphasize that this hybrid scaffold presents promising characteristics for its future application in bone regeneration. - Graphical abstract: B-TCP:HA–alginate hybrid 3D porous scaffolds for application in bone regeneration. - Highlights: • The produced hybrid 3D scaffolds are prone to be applied in bone tissue engineering. • Alginate coated 3D scaffolds present high mechanical and biological properties. • In vitro assays for evaluation of human osteoblast cell attachment in the presence of the scaffolds • The hybrid 3D scaffolds present suitable mechanical and biological properties for use in bone regenerative medicine

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

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Chen, Muwan; Le, Dang QS; Hein, San; Li, Pengcheng; Nygaard, Jens V; Kassem, Moustapha; Kjems, Jørgen; Besenbacher, Flemming; Bünger, Cody

2012-01-01

Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT) cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug. PMID:22904634

Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold

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Zhi-Dong Cao

2016-01-01

Full Text Available Background: Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo. Methods: According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated. Results: In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L, and the function and histomorphology of the liver and kidney were all normal. Conclusion: According to ISO standards, the V-BHA/PAA scaffold

Changes in antibiotic concentrations and antibiotic resistome during commercial composting of animal manures.

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Xie, Wan-Ying; Yang, Xin-Ping; Li, Qian; Wu, Long-Hua; Shen, Qi-Rong; Zhao, Fang-Jie

2016-12-01

The over-use of antibiotics in animal husbandry in China and the concomitant enhanced selection of antibiotic resistance genes (ARGs) in animal manures are of serious concern. Thermophilic composting is an effective way of reducing hazards in organic wastes. However, its effectiveness in antibiotic degradation and ARG reduction in commercial operations remains unclear. In the present study, we determined the concentrations of 15 common veterinary antibiotics and the abundances of 213 ARGs and 10 marker genes for mobile genetic elements (MGEs) in commercial composts made from cattle, poultry and swine manures in Eastern China. High concentrations of fluoroquinolones were found in the poultry and swine composts, suggesting insufficient removal of these antibiotics by commercial thermophilic composting. Total ARGs in the cattle and poultry manures were as high as 1.9 and 5.5 copies per bacterial cell, respectively. After thermophilic composting, the ARG abundance in the mature compost decreased to 9.6% and 31.7% of that in the cattle and poultry manure, respectively. However, some ARGs (e.g. aadA, aadA2, qacEΔ1, tetL) and MGE marker genes (e.g. cintI-1, intI-1 and tnpA-04) were persistent with high abundance in the composts. The antibiotics that were detected at high levels in the composts (e.g. norfloxacin and ofloxacin) might have posed a selection pressure on ARGs. MGE marker genes were found to correlate closely with ARGs at the levels of individual gene, resistance class and total abundance, suggesting that MGEs and ARGs are closely associated in their persistence in the composts under antibiotic selection. Our research shows potential disseminations of antibiotics and ARGs via compost utilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decellularized Human Dental Pulp as a Scaffold for Regenerative Endodontics.

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Song, J S; Takimoto, K; Jeon, M; Vadakekalam, J; Ruparel, N B; Diogenes, A

2017-06-01

Teeth undergo postnatal organogenesis relatively late in life and only complete full maturation a few years after the crown first erupts in the oral cavity. At this stage, development can be arrested if the tooth organ is damaged by either trauma or caries. Regenerative endodontic procedures (REPs) are a treatment alternative to conventional root canal treatment for immature teeth. These procedures rely on the transfer of apically positioned stem cells, including stem cells of the apical papilla (SCAP), into the root canal system. Although clinical success has been reported for these procedures, the predictability of expected outcomes and the organization of the newly formed tissues are affected by the lack of an available suitable scaffold that mimics the complexity of the dental pulp extracellular matrix (ECM). In this study, we evaluated 3 methods of decellularization of human dental pulp to be used as a potential autograft scaffold. Tooth slices of human healthy extracted third molars were decellularized by 3 different methods. One of the methods generated the maximum observed decellularization with minimal impact on the ECM composition and organization. Furthermore, recellularization of the scaffold supported the proliferation of SCAP throughout the scaffold with differentiation into odontoblast-like cells near the dentinal walls. Thus, this study reports that human dental pulp from healthy extracted teeth can be successfully decellularized, and the resulting scaffold supports the proliferation and differentiation of SCAP. The future application of this form of an autograft in REPs can fulfill a yet unmet need for a suitable scaffold, potentially improving clinical outcomes and ultimately promoting the survival and function of teeth with otherwise poor prognosis.

Dosing antibiotics in neonates: review of the pharmacokinetic data.

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Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G

2017-09-01

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

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Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam

OpenAIRE

Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

2015-01-01

The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water ...

Occurrence and dissipation of the antibiotics sulfamethoxazole, sulfadiazine, trimethoprim, and enrofloxacin in the Mekong Delta, Vietnam

OpenAIRE

Das, Surajit; Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

2015-01-01

The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water ...

Actinomycetes: still a source of novel antibiotics.

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Genilloud, Olga

2017-10-18

Covering: 2006 to 2017Actinomycetes have been, for decades, one of the most important sources for the discovery of new antibiotics with an important number of drugs and analogs successfully introduced in the market and still used today in clinical practice. The intensive antibacterial discovery effort that generated the large number of highly potent broad-spectrum antibiotics, has seen a dramatic decline in the large pharma industry in the last two decades resulting in a lack of new classes of antibiotics with novel mechanisms of action reaching the clinic. Whereas the decline in the number of new chemical scaffolds and the rediscovery problem of old known molecules has become a hurdle for industrial natural products discovery programs, new actinomycetes compounds and leads have continued to be discovered and developed to the preclinical stages. Actinomycetes are still one of the most important sources of chemical diversity and a reservoir to mine for novel structures that is requiring the integration of diverse disciplines. These can range from novel strategies to isolate species previously not cultivated, innovative whole cell screening approaches and on-site analytical detection and dereplication tools for novel compounds, to in silico biosynthetic predictions from whole gene sequences and novel engineered heterologous expression, that have inspired the isolation of new NPs and shown their potential application in the discovery of novel antibiotics. This review will address the discovery of antibiotics from actinomycetes from two different perspectives including: (1) an update of the most important antibiotics that have only reached the clinical development in the recent years despite their early discovery, and (2) an overview of the most recent classes of antibiotics described from 2006 to 2017 in the framework of the different strategies employed to untap novel compounds previously overlooked with traditional approaches.

Tomato seeds maturity detection system based on chlorophyll fluorescence

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Li, Cuiling; Wang, Xiu; Meng, Zhijun

2016-10-01

Chlorophyll fluorescence intensity can be used as seed maturity and quality evaluation indicator. Chlorophyll fluorescence intensity of seed coats is tested to judge the level of chlorophyll content in seeds, and further to judge the maturity and quality of seeds. This research developed a detection system of tomato seeds maturity based on chlorophyll fluorescence spectrum technology, the system included an excitation light source unit, a fluorescent signal acquisition unit and a data processing unit. The excitation light source unit consisted of two high power LEDs, two radiators and two constant current power supplies, and it was designed to excite chlorophyll fluorescence of tomato seeds. The fluorescent signal acquisition unit was made up of a fluorescence spectrometer, an optical fiber, an optical fiber scaffolds and a narrowband filter. The data processing unit mainly included a computer. Tomato fruits of green ripe stage, discoloration stage, firm ripe stage and full ripe stage were harvested, and their seeds were collected directly. In this research, the developed tomato seeds maturity testing system was used to collect fluorescence spectrums of tomato seeds of different maturities. Principal component analysis (PCA) method was utilized to reduce the dimension of spectral data and extract principal components, and PCA was combined with linear discriminant analysis (LDA) to establish discriminant model of tomato seeds maturity, the discriminant accuracy was greater than 90%. Research results show that using chlorophyll fluorescence spectrum technology is feasible for seeds maturity detection, and the developed tomato seeds maturity testing system has high detection accuracy.

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model

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Ge Zigang; Tian Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo Jinfei; Cao Tong, E-mail: omscaot@nus.edu.s [Stem Cell Laboratory, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074 (Singapore)

2009-04-15

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models. (communication)

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model

International Nuclear Information System (INIS)

Ge Zigang; Tian Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo Jinfei; Cao Tong

2009-01-01

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models. (communication)

Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution?

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Cheesman, Matthew J.; Ilanko, Aishwarya; Blonk, Baxter; Cock, Ian E.

2017-01-01

The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field. PMID:28989242

A mathematical model for expected time to extinction of pathogenic bacteria through antibiotic

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Ghosh, M. K.; Nandi, S.; Roy, P. K.

2016-04-01

Application of antibiotics in human system to prevent bacterial diseases like Gastritis, Ulcers, Meningitis, Pneumonia and Gonorrhea are indispensable. Antibiotics saved innumerable lives and continue to be a strong support for therapeutic application against pathogenic bacteria. In human system, bacterial diseases occur when pathogenic bacteria gets into the body and begin to reproduce and crowd out healthy bacteria. In this process, immature bacteria releases enzyme which is essential for bacterial cell-wall biosynthesis. After complete formation of cell wall, immature bacteria are converted to mature or virulent bacteria which are harmful to us during bacterial infections. Use of antibiotics as drug inhibits the bacterial cell wall formation. After application of antibiotics within body, the released bacterial enzyme binds with antibiotic molecule instead of its functional site during the cell wall synthesis in a competitive inhibition approach. As a consequence, the bacterial cell-wall formation as well as maturation process of pathogenic bacteria is halted and the disease is cured with lysis of bacterial cells. With this idea, a mathematical model has been developed in the present research investigation to review the inhibition of biosynthesis of bacterial cell wall by the application of antibiotics as drug in the light of enzyme kinetics. This approach helps to estimate the expected time to extinction of the pathogenic bacteria. Our mathematical approach based on the enzyme kinetic model for finding out expected time to extinction contributes favorable results for understanding of disease dynamics. Analytical and numerical results based on simulated findings validate our mathematical model.

A Comparative Study of Bio artificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration

International Nuclear Information System (INIS)

Weng, W.; Song, Sh.; Cao, L.; Chen, X.; Cai, Y.; Li, H.; Zhou, Q.; Zhang, J.; Su, J.

2014-01-01

Bio artificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold), group B (repaired with PLLA/PCL scaffold), and group C (no scaffold) to evaluate the bone-remodeling ability of the implants. Micro-CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffolds in vivo initially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

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Chen M

2012-08-01

Full Text Available Muwan Chen,1,2 Dang QS Le,1,2 San Hein,2 Pengcheng Li,1 Jens V Nygaard,2 Moustapha Kassem,3 Jørgen Kjems,2 Flemming Besenbacher,2 Cody Bünger11Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark; 2Interdisciplinary Nanoscience Center (iNANO, Aarhus University, Aarhus C, Denmark; 3Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, DenmarkAbstract: Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other

Streptokinase Treatment Reverses Biofilm-Associated Antibiotic Resistance in Staphylococcus aureus

DEFF Research Database (Denmark)

Jørgensen, Nis Pedersen; Zobek, Natalia; Dreier, Cindy

2016-01-01

by combining antibiotic treatment with a fibrinolytic drug. We quantified S. aureus USA300 biofilms grown on peg-lids in brain heart infusion (BHI) broth with 0%–50% human plasma. Young (2 h) and mature (24 h) biofilms were then treated with streptokinase to determine if this lead to dispersal. Then......, the minimal biofilm eradication concentration (MBEC) of 24 h old biofilms was measured for vancomycin and daptomycin alone or in combination with 10 µg/mL rifampicin in the presence or absence of streptokinase in the antibiotic treatment step. Finally, biofilms were visualized by confocal laser scanning...... or daptomycin, which are commonly used antibiotics for treatment of S. aureus infections. Fibronolytic drugs have been used to treat thromboembolic events for decades, and our findings suggest that their use against biofilm infections has the potential to improve the efficacy of antibiotics in treatment of S...

Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

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Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

2015-01-01

Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

Ectopic bone formation during tissue-engineered cartilage repair using autologous chondrocytes and novel plasma-derived albumin scaffolds.

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Robla Costales, David; Junquera, Luis; García Pérez, Eva; Gómez Llames, Sara; Álvarez-Viejo, María; Meana-Infiesta, Álvaro

2016-10-01

The aims of this study were twofold: first, to evaluate the production of cartilaginous tissue in vitro and in vivo using a novel plasma-derived scaffold, and second, to test the repair of experimental defects made on ears of New Zealand rabbits (NZr) using this approach. Scaffolds were seeded with chondrocytes and cultured in vitro for 3 months to check in vitro cartilage production. To evaluate in vivo cartilage production, a chondrocyte-seeded scaffold was transplanted subcutaneously to a nude mouse. To check in vivo repair, experimental defects made in the ears of five New Zealand rabbits (NZr) were filled with chondrocyte-seeded scaffolds. In vitro culture produced mature chondrocytes with no extracellular matrix (ECM). Histological examination of redifferentiated in vitro cultures showed differentiated chondrocytes adhered to scaffold pores. Subcutaneous transplantation of these constructs to a nude mouse produced cartilage, confirmed by histological study. Experimental cartilage repair in five NZr showed cartilaginous tissue repairing the defects, mixed with calcified areas of bone formation. It is possible to produce cartilaginous tissue in vivo and to repair experimental auricular defects by means of chondrocyte cultures and the novel plasma-derived scaffold. Further studies are needed to determine the significance of bone formation in the samples. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Preparation of Biopolymeric Nanofiber Containing Silica and Antibiotic

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A. Bagheri Pebdeni

2016-01-01

Full Text Available The biocompatible and biodegradable polymer nanofiber with high potential for anti-bacterial coating are used for: multi-functional membranes, tissue engineering, wound dressings, drug delivery, artificial organs, vascular grafts and etc. Electrospinning nanofiber made of scaffolding due to characteristics such as high surface to volume ratio, high porosity and very fine pores are used for a wide range of applications. In this study, polymer composite nanofiber Silica/chitosan/poly (ethylene oxide /cefepime antibiotic synthesis and antibacterial properties will be discussed. The optimum conditions for preparation of electrospun nanofiber were: voltage; 21 kV, feed rate; 0.5 mL/h, nozzle-collector distance; 10 cm, and chitosan/poly(ethylene oxide weight ratio 90:10 and the volume ratio of chitosan/silica is 70:30.  The antibacterial activity of composite scaffolds were tested by agar plate method by two type bacteria including Escherichia coli and Staphylococcus aureus. With the addition of the silica to chitosan, the hybrid was more biodegradable and improves the mechanical properties of biopolymer.

WiseScaffolder: an algorithm for the semi-automatic scaffolding of Next Generation Sequencing data.

Science.gov (United States)

Farrant, Gregory K; Hoebeke, Mark; Partensky, Frédéric; Andres, Gwendoline; Corre, Erwan; Garczarek, Laurence

2015-09-03

The sequencing depth provided by high-throughput sequencing technologies has allowed a rise in the number of de novo sequenced genomes that could potentially be closed without further sequencing. However, genome scaffolding and closure require costly human supervision that often results in genomes being published as drafts. A number of automatic scaffolders were recently released, which improved the global quality of genomes published in the last few years. Yet, none of them reach the efficiency of manual scaffolding. Here, we present an innovative semi-automatic scaffolder that additionally helps with chimerae resolution and generates valuable contig maps and outputs for manual improvement of the automatic scaffolding. This software was tested on the newly sequenced marine cyanobacterium Synechococcus sp. WH8103 as well as two reference datasets used in previous studies, Rhodobacter sphaeroides and Homo sapiens chromosome 14 (http://gage.cbcb.umd.edu/). The quality of resulting scaffolds was compared to that of three other stand-alone scaffolders: SSPACE, SOPRA and SCARPA. For all three model organisms, WiseScaffolder produced better results than other scaffolders in terms of contiguity statistics (number of genome fragments, N50, LG50, etc.) and, in the case of WH8103, the reliability of the scaffolds was confirmed by whole genome alignment against a closely related reference genome. We also propose an efficient computer-assisted strategy for manual improvement of the scaffolding, using outputs generated by WiseScaffolder, as well as for genome finishing that in our hands led to the circularization of the WH8103 genome. Altogether, WiseScaffolder proved more efficient than three other scaffolders for both prokaryotic and eukaryotic genomes and is thus likely applicable to most genome projects. The scaffolding pipeline described here should be of particular interest to biologists wishing to take advantage of the high added value of complete genomes.

Antibiotic-impregnated articulating cement spacer for infected total knee arthroplasty

Directory of Open Access Journals (Sweden)

Parag Garg

2011-01-01

Full Text Available Background : Standard treatment of chronic infected total knee arthroplasty (TKA is a two-stage revision, the first step being placement of an antibiotic-impregnated cement spacer. Here we describe the results of a new technique (modification of the Goldstien′s technique for intraoperative manufacture of a customized articulating spacer at minimal cost and with relatively good conformity and longevity. Materials and Methods : Thirty-six infected knees underwent this procedure from June 2002 to May 2007. The technique consists of using the freshened femur and tibia interface as molds wrapped in a tin foil for manufacturing the two components of the spacer with antibiotic-impregnated methyl methycrylate cement. We used the spacer and the femoral component of the trial set of a TKA system to mold them to perfect articulation. We also reinforced the spacer with a K-wire scaffold to prevent fracture of the cement mantle in the last 21 cases. Results : All 36 knees showed excellent results in terms of infection control, mobility, and stability. There was significant improvement in the WOMAC and Knee Society Scores (20 and 39 points respectively. There were two fractures of the spacers in the initial 15 cases that did not have K-wire scaffolding but none in the last 21 that had reinforcement. Conclusion : This technique provides a more conforming spacer, with good range of motion and stability. The reinforcement helps in preventing the fracture of the cement mantle and is cost effective.

Gentamicin-Loaded Thermosetting Hydrogel and Moldable Composite Scaffold: Formulation Study and Biologic Evaluation.

Science.gov (United States)

Dorati, Rossella; De Trizio, Antonella; Genta, Ida; Merelli, Alessia; Modena, Tiziana; Conti, Bice

2017-06-01

The aim was to design biodegradable drug delivery systems for gentamicin local delivery, meanwhile acting as scaffold for bone regeneration. Gentamicin-loaded thermosetting composite hydrogels were prepared combining chitosan with bovine bone substitutes (Orthoss® granules), beta-glycerophosphate as cross-linker, and lyophilized to obtain moldable composite scaffolds (moldable composite scaffold loaded with gentamicin [mCSG]). Diverse techniques for gentamicin loading into mCS were investigated by drug incorporation during hydrogel preparation or drug absorption on preformed mCS. Rheologic hydrogel characterization was performed. mCSGs were characterized for porosity, stability (water retention, water uptake), gentamicin release, cell seeding and proliferation, and antimicrobial effect on Escherichia coli ATCC 10356. Results show suitable gentamicin loadings were 4 mg in 1 mL thermosetting composite hydrogel starting solution, irreversible hydrogel thermosetting behavior, and cosolute effect of gentamicin on sol-gel transition. Positive results in terms of porosity (80%-86%), scaffold water uptake, and retention capability were obtained. Antibiotic in vitro release was completed in 4 h. Good cell seeding results were observed for mCSG1-5; mCSG3 and mCSG5 resulted the best as cell proliferation results. mCSG exerted bactericidal effect for 24 h, with superimposition of chitosan bacteriostatic effect in the first 4 h. The results lead to consider the drug delivery for reducing infection risk during bone open surgeries. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Culture of hESC-derived pancreatic progenitors in alginate-based scaffolds.

Science.gov (United States)

Formo, Kjetil; Cho, Candy H-H; Vallier, Ludovic; Strand, Berit L

2015-12-01

The effect of alginate-based scaffolds with added basement membrane proteins on the in vitro development of hESC-derived pancreatic progenitors was investigated. Cell clusters were encapsulated in scaffolds containing the basement membrane proteins collagen IV, laminin, fibronectin, or extracellular matrix-derived peptides, and maintained in culture for up to 46 days. The cells remained viable throughout the experiment with no signs of central necrosis. Whereas nonencapsulated cells aggregated into larger clusters, some of which showed signs of morphological changes and tissue organization, the alginate matrix stabilized the cluster size and displayed more homogeneous cell morphologies, allowing culture for long periods of time. For all conditions tested, a stable or declining expression of insulin and PDX1 and an increase in glucagon and somatostatin over time indicated a progressive reduction in beta cell-related gene expression. Alginate scaffolds can provide a chemically defined, xeno-free and easily scalable alternative for culture of pancreatic progenitors. Although no increase in insulin and PDX1 gene expression after alginate-immobilized cell culture was seen in this study, further optimization of the matrix physicochemical and biological properties and of the medium composition may still be a relevant strategy to promote the stabilization or maturation of stem cell-derived beta cells. © 2015 Wiley Periodicals, Inc.

Multifunctional chitosan/polyvinyl pyrrolidone/45S5 Bioglass® scaffolds for MC3T3-E1 cell stimulation and drug release

Energy Technology Data Exchange (ETDEWEB)

Yao, Qingqing [Institute of Advanced Materials for Nano-Bio Applications, School of Ophthalmology & Optometry, Wenzhou Medical University, 270 Xueyuan Xi Road, Wenzhou, Zhejiang 325027 (China); Li, Wei [Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, Erlangen 91058 (Germany); Yu, Shanshan; Ma, Liwei [Institute of Advanced Materials for Nano-Bio Applications, School of Ophthalmology & Optometry, Wenzhou Medical University, 270 Xueyuan Xi Road, Wenzhou, Zhejiang 325027 (China); Jin, Dayong [Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW 2007 (Australia); Advanced Cytometry Labs, ARC Center of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW 2109 (Australia); Boccaccini, Aldo R., E-mail: Aldo.Boccaccini@ww.uni-erlangen.de [Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, Erlangen 91058 (Germany); Liu, Yong, E-mail: yongliu1980@hotmail.com [Institute of Advanced Materials for Nano-Bio Applications, School of Ophthalmology & Optometry, Wenzhou Medical University, 270 Xueyuan Xi Road, Wenzhou, Zhejiang 325027 (China); Advanced Cytometry Labs, ARC Center of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW 2109 (Australia)

2015-11-01

Novel chitosan–polyvinyl pyrrolidone/45S5 Bioglass® (CS-PVP/BG) scaffolds were prepared via foam replication and chemical cross-linking techniques. The pristine BG, CS-PVP coated BG and genipin cross-linked CS-PVP/BG (G-CS-PVP/BG) scaffolds were synthesized and characterized in terms of chemical composition, physical structure and morphology respectively. Resistance to enzymatic degradation of the scaffold is improved significantly with the use of genipin cross-linked CS-PVP. The bio-effects of scaffolds on MC3T3-E1 osteoblast-like cells were evaluated by studying cell viability, adhesion and proliferation. The CCK-8 assay shows that cell viability on the resulting G-CS-PVP/BG scaffold is improved obviously after cross-linking of genipin. Cell skeleton images exhibit that well-stretched F-actin bundles are obtained on the G-CS-PVP/BG scaffold. SEM results present significant improvement on the cell adhesion and proliferation for cells cultured on the G-CS-PVP/BG scaffold. The drug release performance on the as-synthesized scaffold was studied in a phosphate buffered saline (PBS) solution. Vancomycin is found to be released in burst fashion within 24 h from the pristine BG scaffold, however, the release period from the G-CS-PVP/BG scaffold is enhanced to 7 days, indicating improved drug release properties of the G-CS-PVP/BG scaffold. Our results suggest that the G-CS-PVP/BG scaffolds possess promising physicochemical properties, sustained drug release capability and good biocompatibility for MC3T3-E1 cells' proliferation and adhesion, suggesting their potential applications in areas such as MC3T3-E1 cell stimulation and bone tissue engineering. - Highlights: • Novel genipi–chitosan–polyvinyl pyrrolidone/45S5 Bioglass® scaffolds are prepared. • Resistance to enzymatic degradation of the scaffold is improved significantly. • The resulting scaffold shows enhanced MC3T3-E1 cell adhesion and proliferation. • Release of antibiotic vancomycin from the

Multifunctional chitosan/polyvinyl pyrrolidone/45S5 Bioglass® scaffolds for MC3T3-E1 cell stimulation and drug release

International Nuclear Information System (INIS)

Yao, Qingqing; Li, Wei; Yu, Shanshan; Ma, Liwei; Jin, Dayong; Boccaccini, Aldo R.; Liu, Yong

2015-01-01

Novel chitosan–polyvinyl pyrrolidone/45S5 Bioglass® (CS-PVP/BG) scaffolds were prepared via foam replication and chemical cross-linking techniques. The pristine BG, CS-PVP coated BG and genipin cross-linked CS-PVP/BG (G-CS-PVP/BG) scaffolds were synthesized and characterized in terms of chemical composition, physical structure and morphology respectively. Resistance to enzymatic degradation of the scaffold is improved significantly with the use of genipin cross-linked CS-PVP. The bio-effects of scaffolds on MC3T3-E1 osteoblast-like cells were evaluated by studying cell viability, adhesion and proliferation. The CCK-8 assay shows that cell viability on the resulting G-CS-PVP/BG scaffold is improved obviously after cross-linking of genipin. Cell skeleton images exhibit that well-stretched F-actin bundles are obtained on the G-CS-PVP/BG scaffold. SEM results present significant improvement on the cell adhesion and proliferation for cells cultured on the G-CS-PVP/BG scaffold. The drug release performance on the as-synthesized scaffold was studied in a phosphate buffered saline (PBS) solution. Vancomycin is found to be released in burst fashion within 24 h from the pristine BG scaffold, however, the release period from the G-CS-PVP/BG scaffold is enhanced to 7 days, indicating improved drug release properties of the G-CS-PVP/BG scaffold. Our results suggest that the G-CS-PVP/BG scaffolds possess promising physicochemical properties, sustained drug release capability and good biocompatibility for MC3T3-E1 cells' proliferation and adhesion, suggesting their potential applications in areas such as MC3T3-E1 cell stimulation and bone tissue engineering. - Highlights: • Novel genipi–chitosan–polyvinyl pyrrolidone/45S5 Bioglass® scaffolds are prepared. • Resistance to enzymatic degradation of the scaffold is improved significantly. • The resulting scaffold shows enhanced MC3T3-E1 cell adhesion and proliferation. • Release of antibiotic vancomycin from the

Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

International Nuclear Information System (INIS)

Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D’Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

2017-01-01

The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds. Thus, besides expressing specific enzymes for drugs degradation, Gram-negative bacteria can also resist by modulating the influx and efflux of antibiotics, keeping the internal concentration low. However, there are no direct and robust experimental methods capable of measuring the permeability of small molecules, thus severely limiting our knowledge of the molecular mechanisms that ultimately control the permeation of antibiotics through the outer membrane. This is the innovation gap to be filled for Gram-negative bacteria. This review is focused on the permeation of small molecules through porins, considered the main path for the entry of polar antibiotics into Gram-negative bacteria. A fundamental understanding of how these proteins are able to filter small molecules is a prerequisite to design/optimize antibacterials with improved permeation. The level of sophistication of modern molecular modeling algorithms and the advances in new computer hardware has made the simulation of such complex processes possible at the molecular level. In this work we aim to share our experience and perspectives in the context of a multidisciplinary extended collaboration within the IMI

Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

Science.gov (United States)

Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D'Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

2017-03-01

The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds. Thus, besides expressing specific enzymes for drugs degradation, Gram-negative bacteria can also resist by modulating the influx and efflux of antibiotics, keeping the internal concentration low. However, there are no direct and robust experimental methods capable of measuring the permeability of small molecules, thus severely limiting our knowledge of the molecular mechanisms that ultimately control the permeation of antibiotics through the outer membrane. This is the innovation gap to be filled for Gram-negative bacteria. This review is focused on the permeation of small molecules through porins, considered the main path for the entry of polar antibiotics into Gram-negative bacteria. A fundamental understanding of how these proteins are able to filter small molecules is a prerequisite to design/optimize antibacterials with improved permeation. The level of sophistication of modern molecular modeling algorithms and the advances in new computer hardware has made the simulation of such complex processes possible at the molecular level. In this work we aim to share our experience and perspectives in the context of a multidisciplinary extended collaboration within the IMI

Engineered porous scaffolds for periprosthetic infection prevention

Energy Technology Data Exchange (ETDEWEB)

Iviglia, Giorgio, E-mail: giorgio.iviglia@polito.it [Nobil Bio Ricerche Srl, 14037 Portacomaro (Italy); Department of Applied Science and Technology, Institute of Materials Physics and Engineering, Politecnico di Torino, 10121 Torino (Italy); Cassinelli, Clara; Bollati, Daniele [Nobil Bio Ricerche Srl, 14037 Portacomaro (Italy); Baino, Francesco [Department of Applied Science and Technology, Institute of Materials Physics and Engineering, Politecnico di Torino, 10121 Torino (Italy); Torre, Elisa; Morra, Marco [Nobil Bio Ricerche Srl, 14037 Portacomaro (Italy); Vitale-Brovarone, Chiara [Department of Applied Science and Technology, Institute of Materials Physics and Engineering, Politecnico di Torino, 10121 Torino (Italy)

2016-11-01

Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1 week, the engineered construct still inhibits the bacterial growth. Degradation tests show an excellent behavior in a physiological and acidic environment (< 10% of mass loss). Furthermore, the PEI coating shows an anti-inflammatory response, and good cell proliferation and migration were demonstrated in vitro using osteoblast SAOS-2 cell line. This new engineered construct exhibits excellent properties both as an antibacterial material and as a stimulator of bone formation, which makes it a good candidate to contrast periprosthetic infection. - Highlights: • A novel three-dimensional ceramic scaffold was developed for infection prevention. • Pectin/chitosan coating stabilizes the degradation behavior in acidic environment. • Polyelectrolyte complex allows sustained release of vancomycin. • Inhibition of bacterial proliferation and biofilm formation was assessed. • PEI coating elicits anti-inflammatory response.

Engineered porous scaffolds for periprosthetic infection prevention

International Nuclear Information System (INIS)

Iviglia, Giorgio; Cassinelli, Clara; Bollati, Daniele; Baino, Francesco; Torre, Elisa; Morra, Marco; Vitale-Brovarone, Chiara

2016-01-01

Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1 week, the engineered construct still inhibits the bacterial growth. Degradation tests show an excellent behavior in a physiological and acidic environment (< 10% of mass loss). Furthermore, the PEI coating shows an anti-inflammatory response, and good cell proliferation and migration were demonstrated in vitro using osteoblast SAOS-2 cell line. This new engineered construct exhibits excellent properties both as an antibacterial material and as a stimulator of bone formation, which makes it a good candidate to contrast periprosthetic infection. - Highlights: • A novel three-dimensional ceramic scaffold was developed for infection prevention. • Pectin/chitosan coating stabilizes the degradation behavior in acidic environment. • Polyelectrolyte complex allows sustained release of vancomycin. • Inhibition of bacterial proliferation and biofilm formation was assessed. • PEI coating elicits anti-inflammatory response.

Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs

Directory of Open Access Journals (Sweden)

Nicola Baldini

2012-02-01

Full Text Available In bone engineering, the adhesion, proliferation and differentiation of mesenchymal stromal cells rely on signaling from chemico-physical structure of the substrate, therefore prompting the design of mimetic “extracellular matrix”-like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA-based scaffolds have been mixed with different components, including single walled carbon nanotubes (CNT, micro-hydroxyapatite particles (HA, and BMP2, and treated with plasma (PT, to obtain four different nanocomposites: PLLA + CNT, PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow mesenchymal stromal cells (MSCs were derived from the femur of orthopaedic patients, seeded on the scaffolds and cultured under osteogenic induction up to differentiation and mineralization. The release of specific metabolites and temporal gene expression profiles of marrow-derived osteoprogenitors were analyzed at definite time points, relevant to in vitro culture as well as in vivo differentiation. As a result, the role of the different biomimetic components added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the highest biomimetic activity on cells differentiating to mature osteoblasts. The modification of a polymeric scaffold with reinforcing components which also work as biomimetic cues for cells can effectively direct osteoprogenitor cells differentiation, so as to shorten the time required for mineralization.

Using in vitro maturation and cell-free expression to explore [FeFe] hydrogenase activation and protein scaffolding requirements

Energy Technology Data Exchange (ETDEWEB)

Swartz, James [Stanford Univ., CA (United States)

2017-01-25

Final Project Report describing work to elucidate mechanisms for the activation of [FeFe]-hydrogenases and to explore the impact of the polypeptide scaffolding on the function of the Fe-S redox and catalytic centers with emphasis on improving oxygen tolerance.

Scaffolded biology.

Science.gov (United States)

Minelli, Alessandro

2016-09-01

Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

Custom-Made Computer-Aided-Design/Computer-Aided-Manufacturing Biphasic Calcium-Phosphate Scaffold for Augmentation of an Atrophic Mandibular Anterior Ridge

Directory of Open Access Journals (Sweden)

Francesco Guido Mangano

2015-01-01

Full Text Available This report documents the clinical, radiographic, and histologic outcome of a custom-made computer-aided-design/computer-aided-manufactured (CAD/CAM scaffold used for the alveolar ridge augmentation of a severely atrophic anterior mandible. Computed tomographic (CT images of an atrophic anterior mandible were acquired and modified into a 3-dimensional (3D reconstruction model; this was transferred to a CAD program, where a custom-made scaffold was designed. CAM software generated a set of tool-paths for the manufacture of the scaffold on a computer-numerical-control milling machine into the exact shape of the 3D design. A custom-made scaffold was milled from a synthetic micromacroporous biphasic calcium phosphate (BCP block. The scaffold closely matched the shape of the defect: this helped to reduce the time for the surgery and contributed to good healing. One year later, newly formed and well-integrated bone was clinically available, and two implants (AnyRidge, MegaGen, Gyeongbuk, South Korea were placed. The histologic samples retrieved from the implant sites revealed compact mature bone undergoing remodelling, marrow spaces, and newly formed trabecular bone surrounded by residual BCP particles. This study demonstrates that custom-made scaffolds can be fabricated by combining CT scans and CAD/CAM techniques. Further studies on a larger sample of patients are needed to confirm these results.

Response of bone marrow stromal cells to graded co-electrospun scaffolds and its implications for engineering the ligament-bone interface.

Science.gov (United States)

Samavedi, Satyavrata; Guelcher, Scott A; Goldstein, Aaron S; Whittington, Abby R

2012-11-01

Biomaterial scaffolds with gradients in architecture, mechanical and chemical properties have the potential to improve the osseointegration of ligament grafts by recapitulating phenotypic gradients that exist at the natural ligament-bone (L-B) interface. Towards the larger goal of regenerating the L-B interface, this in vitro study was performed to investigate the potential of two scaffolds with mineral gradients in promoting a spatial gradient of osteoblastic differentiation. Specifically, the first graded scaffold was fabricated by co-electrospinning two polymer solutions (one doped with nano-hydroxyapatite particles) from offset spinnerets, while the second was created by immersing the first scaffold in a 5 × simulated body fluid. Rat bone marrow stromal cells, cultured in the presence of osteogenic supplements, were found to be metabolically active on all regions of both scaffolds after 1 and 7 days of culture. Gene expression of bone morphogenic protein-2 and osteopontin was elevated on mineral-containing regions as compared to regions without mineral, while the expression of alkaline phosphatase mRNA revealed the opposite trend. Finally, the presence of osteopontin and bone sialoprotein confirmed osteoblastic phenotypic maturation by day 28. This study indicates that co-electrospun scaffolds with gradients in mineral content can guide the formation of phenotypic gradients and may thus promote the regeneration of the L-B interface. Copyright © 2012 Elsevier Ltd. All rights reserved.

Parallel fabrication of macroporous scaffolds.

Science.gov (United States)

Dobos, Andrew; Grandhi, Taraka Sai Pavan; Godeshala, Sudhakar; Meldrum, Deirdre R; Rege, Kaushal

2018-07-01

Scaffolds generated from naturally occurring and synthetic polymers have been investigated in several applications because of their biocompatibility and tunable chemo-mechanical properties. Existing methods for generation of 3D polymeric scaffolds typically cannot be parallelized, suffer from low throughputs, and do not allow for quick and easy removal of the fragile structures that are formed. Current molds used in hydrogel and scaffold fabrication using solvent casting and porogen leaching are often single-use and do not facilitate 3D scaffold formation in parallel. Here, we describe a simple device and related approaches for the parallel fabrication of macroporous scaffolds. This approach was employed for the generation of macroporous and non-macroporous materials in parallel, in higher throughput and allowed for easy retrieval of these 3D scaffolds once formed. In addition, macroporous scaffolds with interconnected as well as non-interconnected pores were generated, and the versatility of this approach was employed for the generation of 3D scaffolds from diverse materials including an aminoglycoside-derived cationic hydrogel ("Amikagel"), poly(lactic-co-glycolic acid) or PLGA, and collagen. Macroporous scaffolds generated using the device were investigated for plasmid DNA binding and cell loading, indicating the use of this approach for developing materials for different applications in biotechnology. Our results demonstrate that the device-based approach is a simple technology for generating scaffolds in parallel, which can enhance the toolbox of current fabrication techniques. © 2018 Wiley Periodicals, Inc.

Bioengineering pediatric scaffold-free auricular cartilaginous constructs.

Science.gov (United States)

Akbari, Pedram; Waldman, Stephen D; Cushing, Sharon L; Papsin, Blake C; Propst, Evan J; Weber, Joanna F; Yeger, Herman; Farhat, Walid A

2017-05-01

The use of exogenous materials as scaffolds in cartilage tissue engineering has limited the clinical application of resultant constructs due to the risk of postoperative complications. In an effort to minimize such complications, we aim to generate human, scaffold-free auricular cartilaginous constructs. Laboratory study using pediatric auricular cartilage. Remnant, normal pediatric auricular cartilage samples that would have otherwise been discarded were collected and digested to free cells. Harvested cells were cultured and expanded in vitro for two passages and plated as micromass cultures. The culture medium was replaced with a chemically defined chondrogenic medium, and cellular monolayers surrounding micromass cultures were continuously scraped off. Constructs were allowed to mature for a period of 8 weeks. Micromass constructs showed mechanical stability and structurally resembled native auricular tissue, with a perichondrium-like layer of cells surrounding the inner cartilaginous zone. Constructs accumulated equivalent sulphated glycosaminoglycan and 50% of collagen content compared to native auricular cartilage by mass, while displaying 156% more cellularity. High-density micromass cultures of pediatric auricular chondrocytes can generate stable cartilaginous constructs following prolonged chondrogenic inductions in vitro. This technique is an essential step toward the development of three-dimensional constructs to recreate clinically applicable auricular cartilaginous constructs. NA. Laryngoscope, 127:E153-E158, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry

Science.gov (United States)

Dimova, Dilyana; Stumpfe, Dagmar; Hu, Ye; Bajorath, Jürgen

2016-01-01

Aim: Computational design of and systematic search for a new type of molecular scaffolds termed analog series-based scaffolds. Materials & methods: From currently available bioactive compounds, analog series were systematically extracted, key compounds identified and new scaffolds isolated from them. Results: Using our computational approach, more than 12,000 scaffolds were extracted from bioactive compounds. Conclusion: A new scaffold definition is introduced and a computational methodology developed to systematically identify such scaffolds, yielding a large freely available scaffold knowledge base. PMID:28116132

Use of Interim Scaffolding and Neotissue Development to Produce a Scaffold-Free Living Hyaline Cartilage Graft.

Science.gov (United States)

Lau, Ting Ting; Leong, Wenyan; Peck, Yvonne; Su, Kai; Wang, Dong-An

2015-01-01

The fabrication of three-dimensional (3D) constructs relies heavily on the use of biomaterial-based scaffolds. These are required as mechanical supports as well as to translate two-dimensional cultures to 3D cultures for clinical applications. Regardless of the choice of scaffold, timely degradation of scaffolds is difficult to achieve and undegraded scaffold material can lead to interference in further tissue development or morphogenesis. In cartilage tissue engineering, hydrogel is the highly preferred scaffold material as it shares many similar characteristics with native cartilaginous matrix. Hence, we employed gelatin microspheres as porogens to create a microcavitary alginate hydrogel as an interim scaffold to facilitate initial chondrocyte 3D culture and to establish a final scaffold-free living hyaline cartilaginous graft (LhCG) for cartilage tissue engineering.

A 3D nanofibrous hydrogel and collagen sponge scaffold promotes locomotor functional recovery, spinal repair, and neuronal regeneration after complete transection of the spinal cord in adult rats

International Nuclear Information System (INIS)

Kaneko, Ai; Matsushita, Akira; Sankai, Yoshiyuki

2015-01-01

Central nervous system neurons in adult mammals display limited regeneration after injury, and functional recovery is poor following complete transection (>4 mm gap) of a rat spinal cord. A novel combination scaffold composed of 3D nanofibrous hydrogel PuraMatrix and a honeycomb collagen sponge was used to promote spinal repair and locomotor functional recovery following complete transection of the spinal cord in rats. We transplanted this scaffold into 5 mm spinal cord gaps and assessed spinal repair and functional recovery using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. The BBB score of the scaffold-transplanted group was significantly higher than that of the PBS-injected control group from 24 d to 4 months after the operation (P < 0.001–0.01), reaching 6.0  ±  0.75 (mean ± SEM) in the transplant and 0.70  ±  0.46 in the control groups. Neuronal regeneration and spinal repair were examined histologically using Pan Neuronal Marker, glial fibrillary acidic protein, growth-associated protein 43, and DAPI. The scaffolds were well integrated into the spinal cords, filling the 5 mm gaps with higher numbers of regenerated and migrated neurons, astrocytes, and other cells than in the control group. Mature and immature neurons and astrocytes in the scaffolds became colocalized and aligned longitudinally over >2 mm, suggesting their differentiation, maturation, and function. The spinal cord NF200 content of the transplant group, analyzed by western blot, was more than twice that of the control group, supporting the histological results. Transplantation of this novel scaffold promoted functional recovery, spinal repair, and neuronal regeneration. (paper)

Antimicrobial Cu-bearing stainless steel scaffolds

Energy Technology Data Exchange (ETDEWEB)

Wang, Qiang, E-mail: mfqwang@163.com [School of Stomatology, China Medical University, Shenyang 110002 (China); Ren, Ling [Institute of Metal Research, Chinese Academy of Sciences (China); Li, Xiaopeng [School of Mechanical and Chemical Engineering, The University of Western Australia (Australia); Zhang, Shuyuan [Institute of Metal Research, Chinese Academy of Sciences (China); Sercombe, Timothy B., E-mail: tim.sercombe@uwa.edu.au [School of Mechanical and Chemical Engineering, The University of Western Australia (Australia); Yang, Ke, E-mail: kyang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences (China)

2016-11-01

Copper-bearing stainless steel scaffolds with two different structures (Body Centered Cubic and Gyroid labyrinth) at two solid fractions (25% and 40%) were fabricated from both 316L powder and a mixture of 316L and elemental Cu powder using selective laser melting, and relative 316L scaffolds were served as control group. After processing, the antimicrobial testing demonstrated that the 316L-Cu scaffolds presented excellent antimicrobial activity against Escherichia coli and Staphylococcus aureus, and the cell viability assay indicated that there was no cytotoxic effect of 316L-Cu scaffolds on rat marrow mesenchymal stem cells. As such, these have the potential to reduce implant-associated infections. The Cu was also found to homogeneously distribute within the microstructure by scanning electronic microcopy. The addition of Cu would not significantly affect its strength and stiffness compared to 316L scaffold, and the stiffness of all the scaffolds (3-20GPa) is similar to that of bone and much less than that of bulk stainless steel. Consequently, fabrication of such low stiffness porous structures, especially coupled with the addition of antimicrobial Cu, may provide a new direction for medical stainless steels. - Highlights: • 316L-Cu scaffolds were fabricated by using selective laser melting (SLM). • 316L-Cu scaffolds showed satisfied antimicrobial activities. • 316L-Cu scaffolds have no cytotoxic effect on normal cells. • Other properties of 316L-Cu scaffolds were similar to 316L scaffolds. • 316L-Cu scaffolds have the potential to be used in orthopedic applications.

Antimicrobial Cu-bearing stainless steel scaffolds

International Nuclear Information System (INIS)

Wang, Qiang; Ren, Ling; Li, Xiaopeng; Zhang, Shuyuan; Sercombe, Timothy B.; Yang, Ke

2016-01-01

Copper-bearing stainless steel scaffolds with two different structures (Body Centered Cubic and Gyroid labyrinth) at two solid fractions (25% and 40%) were fabricated from both 316L powder and a mixture of 316L and elemental Cu powder using selective laser melting, and relative 316L scaffolds were served as control group. After processing, the antimicrobial testing demonstrated that the 316L-Cu scaffolds presented excellent antimicrobial activity against Escherichia coli and Staphylococcus aureus, and the cell viability assay indicated that there was no cytotoxic effect of 316L-Cu scaffolds on rat marrow mesenchymal stem cells. As such, these have the potential to reduce implant-associated infections. The Cu was also found to homogeneously distribute within the microstructure by scanning electronic microcopy. The addition of Cu would not significantly affect its strength and stiffness compared to 316L scaffold, and the stiffness of all the scaffolds (3-20GPa) is similar to that of bone and much less than that of bulk stainless steel. Consequently, fabrication of such low stiffness porous structures, especially coupled with the addition of antimicrobial Cu, may provide a new direction for medical stainless steels. - Highlights: • 316L-Cu scaffolds were fabricated by using selective laser melting (SLM). • 316L-Cu scaffolds showed satisfied antimicrobial activities. • 316L-Cu scaffolds have no cytotoxic effect on normal cells. • Other properties of 316L-Cu scaffolds were similar to 316L scaffolds. • 316L-Cu scaffolds have the potential to be used in orthopedic applications.

Antibiotic innovation for future public health needs.

Science.gov (United States)

Theuretzbacher, U

2017-10-01

The public health threat of antibiotic resistance has gained attention at the highest political levels globally, and recommendations on how to respond are being considered for implementation. Among the recommended responses being explored for their feasibility is the introduction of economic incentives to promote research and development of new antibiotics. There is broad agreement that public investment should stimulate innovation and be linked to policies promoting sustainable and equitable access to antibiotics. Though commonly used, the term 'innovation' is not based on a common understanding. This article aims to initiate discussion on the meaning of 'innovation' in this context. Literature and expert opinion. As the definition of a novel class (novel scaffold, novel pharmacophore), a novel target (novel binding site) and a novel mode of action-the three traditional criteria for 'innovation' in this context-may be confounded by the complexities of antibacterial drug discovery, a biological and outcome-oriented definition of innovation is presented to initiate discussion. Such an expanded definition of innovation in this specific context is based on the overarching requirement that a drug not be affected by cross-resistance to existing drugs in the organisms and indications for which it is intended to be used, and that it have low potential for high-frequency, high-level single-step resistance if intended as a single drug therapy. Policy makers, public health authorities and funders could use such a comprehensive definition of innovation to prioritize where publicly funded incentives should be applied. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Computational design of new molecular scaffolds for medicinal chemistry, part II: generalization of analog series-based scaffolds

Science.gov (United States)

Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

2018-01-01

Aim: Extending and generalizing the computational concept of analog series-based (ASB) scaffolds. Materials & methods: Methodological modifications were introduced to further increase the coverage of analog series (ASs) and compounds by ASB scaffolds. From bioactive compounds, ASs were systematically extracted and second-generation ASB scaffolds isolated. Results: More than 20,000 second-generation ASB scaffolds with single or multiple substitution sites were extracted from active compounds, achieving more than 90% coverage of ASs. Conclusion: Generalization of the ASB scaffold approach has yielded a large knowledge base of scaffold-capturing compound series and target information. PMID:29379641

Cell–scaffold interaction within engineered tissue

Energy Technology Data Exchange (ETDEWEB)

Chen, Haiping; Liu, Yuanyuan, E-mail: Yuanyuan_liu@shu.edu.cn; Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

2014-05-01

The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

Using Scaffolds in Problem-Based Hypermedia

Science.gov (United States)

Su, Yuyan; Klein, James D.

2010-01-01

This study investigated the use of scaffolds in problem-based hypermedia. Three hundred and twelve undergraduate students enrolled in a computer literacy course worked in project teams to use a hypermedia PBL program focused on designing a personal computer. The PBL program included content scaffolds, metacognitive scaffolds, or no scaffolds.…

Bioactive polymeric scaffolds for tissue engineering

Directory of Open Access Journals (Sweden)

Scott Stratton

2016-12-01

Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

Ligament regeneration using an absorbable stent-shaped poly-L-lactic acid scaffold in a rabbit model.

Science.gov (United States)

Nishimoto, Hanako; Kokubu, Takeshi; Inui, Atsuyuki; Mifune, Yutaka; Nishida, Kotaro; Fujioka, Hiroyuki; Yokota, Kumiko; Hiwa, Chiaki; Kurosaka, Masahiro

2012-11-01

Ligaments are frequently damaged in sports activities and trauma, and severe ligament injury can lead to joint instability and osteoarthritis. In this study, we aimed to regenerate the medial collateral ligament (MCL) using an absorbable stent-shaped poly-L-lactic acid (PLLA) scaffold in a rabbit model to examine the biocompatibility and mechanical properties. Twenty-three Japanese white rabbits were used in this study. MCL defects were surgically created in the knee joints and then reconstructed using stent-shaped PLLA scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into the contralateral knees. Seven rabbits were sacrificed at three time points, conducted four, eight and 16 weeks after the operation. The regenerated tissues were histologically evaluated using fibre alignment scoring, morphology of fibroblast scoring and immunohistochemical analysis of types I and III collagen. The regenerated tissues were also biomechanically evaluated by measuring the ultimate failure load and stiffness. At four weeks post-operation, spindle-shaped cells were observed on the inside of the scaffolds. At eight weeks, maturation of the regenerated tissues and collagen fibre alignment parallel to the ligaments was observed. At 16 weeks, the fibre alignment had become denser. The fibre alignment and morphology of fibroblast scores significantly increased in a time-dependent manner. Expression of type I collagen was more strongly observed in the scaffold group at eight and 16 weeks post-operation than at four weeks. Type III collagen was also observed at four, eight and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the ligament-bone junction at eight and 16 weeks. The ultimate failure load of the scaffold group was 46.7 ± 20.7 N, 66.5 ± 11.0 N and 74.3 ± 11.5 N at four, eight and 16 weeks post-operation, respectively. There was no statistical difference between the normal MCL and the scaffold group at 16 weeks post

Semiotic scaffolding

DEFF Research Database (Denmark)

Hoffmeyer, Jesper

2015-01-01

Life processes at all levels (from the genetic to the behavioral) are coordinated by semiotic interactions between cells, tissues, membranes, organs, or individuals and tuned through evolution to stabilize important functions. A stabilizing dynamics based on a system of semiotic scaffoldings impl...... semiotic scaffolding is not, of course, exclusive for phylogenetic and ontogenetic development, it is also an important dynamical element in cultural evolution.......Life processes at all levels (from the genetic to the behavioral) are coordinated by semiotic interactions between cells, tissues, membranes, organs, or individuals and tuned through evolution to stabilize important functions. A stabilizing dynamics based on a system of semiotic scaffoldings...... (the representamen) and the effect. Semiotic interaction patterns therefore provide fast and versatile mechanisms for adaptations, mechanisms that depend on communication and “learning” rather than on genetic preformation. Seen as a stabilizing agency supporting the emergence of higher-order structure...

SHOP: scaffold hopping by GRID-based similarity searches

DEFF Research Database (Denmark)

Bergmann, Rikke; Linusson, Anna; Zamora, Ismael

2007-01-01

A new GRID-based method for scaffold hopping (SHOP) is presented. In a fully automatic manner, scaffolds were identified in a database based on three types of 3D-descriptors. SHOP's ability to recover scaffolds was assessed and validated by searching a database spiked with fragments of known...... scaffolds were in the 31 top-ranked scaffolds. SHOP also identified new scaffolds with substantially different chemotypes from the queries. Docking analysis indicated that the new scaffolds would have similar binding modes to those of the respective query scaffolds observed in X-ray structures...

Alginate based scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Valente, J.F.A.; Valente, T.A.M. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Alves, P.; Ferreira, P. [CIEPQPF, Departamento de Engenharia Quimica, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Silva, A. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

2012-12-01

The design and production of scaffolds for bone tissue regeneration is yet unable to completely reproduce the native bone properties. In the present study new alginate microparticle and microfiber aggregated scaffolds were produced to be applied in this area of regenerative medicine. The scaffolds' mechanical properties were characterized by thermo mechanical assays. Their morphological characteristics were evaluated by isothermal nitrogen adsorption and scanning electron microscopy. The density of both types of scaffolds was determined by helium pycnometry and mercury intrusion porosimetry. Furthermore, scaffolds' cytotoxic profiles were evaluated in vitro by seeding human osteoblast cells in their presence. The results obtained showed that scaffolds have good mechanical and morphological properties compatible with their application as bone substitutes. Moreover, scaffold's biocompatibility was confirmed by the observation of cell adhesion and proliferation after 5 days of being seeded in their presence and by non-radioactive assays. - Highlights: Black-Right-Pointing-Pointer Design and production of scaffolds for bone tissue regeneration. Black-Right-Pointing-Pointer Microparticle and microfiber alginate scaffolds were produced through a particle aggregation technique; Black-Right-Pointing-Pointer Scaffolds' mechanically and biologically properties were characterized through in vitro studies;.

Changes in the stability and biomechanics of P22 bacteriophage capsid during maturation.

Science.gov (United States)

Kant, Ravi; Llauró, Aida; Rayaprolu, Vamseedhar; Qazi, Shefah; de Pablo, Pedro J; Douglas, Trevor; Bothner, Brian

2018-03-15

The capsid of P22 bacteriophage undergoes a series of structural transitions during maturation that guide it from spherical to icosahedral morphology. The transitions include the release of scaffold proteins and capsid expansion. Although P22 maturation has been investigated for decades, a unified model that incorporates thermodynamic and biophysical analyses is not available. A general and specific model of icosahedral capsid maturation is of significant interest to theoreticians searching for fundamental principles as well as virologists and material scientists seeking to alter maturation to their advantage. To address this challenge, we have combined the results from orthogonal biophysical techniques including differential scanning fluorimetry, atomic force microscopy, circular dichroism, and hydrogen-deuterium exchange mass spectrometry. By integrating these results from single particle and population measurements, an energy landscape of P22 maturation from procapsid through expanded shell to wiffle ball emerged, highlighting the role of metastable structures and the thermodynamics guiding maturation. The propagation of weak quaternary interactions across symmetric elements of the capsid is a key component for stability in P22. A surprising finding is that the progression to wiffle ball, which lacks pentamers, shows that chemical and thermal stability can be uncoupled from mechanical rigidity, elegantly demonstrating the complexity inherent in capsid protein interactions and the emergent properties that can arise from icosahedral symmetry. On a broader scale, this work demonstrates the power of applying orthogonal biophysical techniques to elucidate assembly mechanisms for supramolecular complexes and provides a framework within which other viral systems can be compared. Copyright © 2018 Elsevier B.V. All rights reserved.

Biocomposite scaffolds for bone regeneration: Role of chitosan and hydroxyapatite within poly-3-hydroxybutyrate-co-3-hydroxyvalerate on mechanical properties and in vitro evaluation.

Science.gov (United States)

Zhang, Sai; Prabhakaran, Molamma P; Qin, Xiaohong; Ramakrishna, Seeram

2015-11-01

Bio-engineered scaffolds for bone tissue regeneration is an exploding area of research mainly because they can satisfy the essential demands and current challenges in bone replacement therapies, by imitating the extracellular matrix (ECM) of the native bone. We fabricated bio-composite nanofibrous scaffolds with a blend of poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV), chitosan (CTS) and hydroxyapatite (HA) during this study. Morphological evaluation confirmed the fiber diameters of PHBV, PHBV/CTS (90:10), PHBV/CTS/HA4 (85.5:9.5:5) and PHBV/CTS/HA8 (81:9:10) as 405 ± 74 nm, 334 ± 82 nm, 316 ± 103 nm and 256 ± 110 nm, respectively. The PHBV/CTS/HA4 and PHBV/CTS/HA8 scaffolds were capable of enduring the long term culture of human fetal osteoblasts (hFOB) with ultimate tensile strength of 3.55 ± 0.22 MPa and 4.19 ± 0.19 MPa, respectively. The proliferation of osteoblasts on PHBV/CTS/HA8 scaffold was found 34.10% higher than that on PHBV scaffold on day 20. Cell maturation identified by alkaline phosphatase activity on day 20 was significantly higher on PHBV/CTS/HA8 scaffold than that on PHBV scaffold. The cells on PHBV/CTS/HA8 scaffold also acquired higher mineral deposition (25.79%) than the mineral deposition on PHBV scaffold by day 20, confirmed by EDX analysis. Based on the results, we concluded that the electrospun PHBV/CTS/HA8 scaffolds hold great potential to promote the regeneration of bone tissue due to the synergistic effect of chitosan and HA, whereby chitosan provided cell recognition sites while HA acted as a chelating agent for organizing the apatite-like mineralization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developmental Scaffolding

DEFF Research Database (Denmark)

Giorgi, Franco; Bruni, Luis Emilio

2015-01-01

. Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. Awide range of genetic, cellular and morphological mechanisms allows the scaffolding to integrate these modular variations...... to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones...

Modifying bone scaffold architecture in vivo with permanent magnets to facilitate fixation of magnetic scaffolds.

Science.gov (United States)

Panseri, S; Russo, A; Sartori, M; Giavaresi, G; Sandri, M; Fini, M; Maltarello, M C; Shelyakova, T; Ortolani, A; Visani, A; Dediu, V; Tampieri, A; Marcacci, M

2013-10-01

The fundamental elements of tissue regeneration are cells, biochemical signals and the three-dimensional microenvironment. In the described approach, biomineralized-collagen biomaterial functions as a scaffold and provides biochemical stimuli for tissue regeneration. In addition superparamagnetic nanoparticles were used to magnetize the biomaterials with direct nucleation on collagen fibres or impregnation techniques. Minimally invasive surgery was performed on 12 rabbits to implant cylindrical NdFeB magnets in close proximity to magnetic scaffolds within the lateral condyles of the distal femoral epiphyses. Under this static magnetic field we demonstrated, for the first time in vivo, that the ability to modify the scaffold architecture could influence tissue regeneration obtaining a well-ordered tissue. Moreover, the association between NdFeB magnet and magnetic scaffolds represents a potential technique to ensure scaffold fixation avoiding micromotion at the tissue/biomaterial interface. © 2013.

Computational Exploration of Molecular Scaffolds in Medicinal Chemistry.

Science.gov (United States)

Hu, Ye; Stumpfe, Dagmar; Bajorath, Jürgen

2016-05-12

The scaffold concept is widely applied in medicinal chemistry. Scaffolds are mostly used to represent core structures of bioactive compounds. Although the scaffold concept has limitations and is often viewed differently from a chemical and computational perspective, it has provided a basis for systematic investigations of molecular cores and building blocks, going far beyond the consideration of individual compound series. Over the past 2 decades, alternative scaffold definitions and organization schemes have been introduced and scaffolds have been studied in a variety of ways and increasingly on a large scale. Major applications of the scaffold concept include the generation of molecular hierarchies, structural classification, association of scaffolds with biological activities, and activity prediction. This contribution discusses computational approaches for scaffold generation and analysis, with emphasis on recent developments impacting medicinal chemistry. A variety of scaffold-based studies are discussed, and a perspective on scaffold methods is provided.

In Vitro Degradation of PHBV Scaffolds and nHA/PHBV Composite Scaffolds Containing Hydroxyapatite Nanoparticles for Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Naznin Sultana

2012-01-01

Full Text Available This paper investigated the long-term in vitro degradation properties of scaffolds based on biodegradable polymers and osteoconductive bioceramic/polymer composite materials for the application of bone tissue engineering. The three-dimensional porous scaffolds were fabricated using emulsion-freezing/freeze-drying technique using poly(hydroxybutyrate-co-hydroxyvalerate (PHBV which is a natural biodegradable and biocompatible polymer. Nanosized hydroxyapatite (nHA particles were successfully incorporated into the PHBV scaffolds to render the scaffolds osteoconductive. The PHBV and nHA/PHBV scaffolds were systematically evaluated using various techniques in terms of mechanical strength, porosity, porous morphology, and in vitro degradation. PHBV and nHA/PHBV scaffolds degraded over time in phosphate-buffered saline at 37°C. PHBV polymer scaffolds exhibited slow molecular weight loss and weight loss in the in vitro physiological environment. Accelerated weight loss was observed in nHA incorporated PHBV composite scaffolds. An increasing trend of crystallinity was observed during the initial period of degradation time. The compressive properties decreased more than 40% after 5-month in vitro degradation. Together with interconnected pores, high porosity, suitable mechanical properties, and slow degradation profile obtained from long-term degradation studies, the PHBV scaffolds and osteoconductive nHA/PHBV composite scaffolds showed promises for bone tissue engineering application.

Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

International Nuclear Information System (INIS)

Lopez, Soledad; Gomez, Enrique; Torres, Maria J.; Pozo, David; Fernandez, Tahia D.; Ariza, Adriana; Sanz, Maria L.; Blanca, Miguel; Mayorga, Cristobalina

2015-01-01

The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.

Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

Energy Technology Data Exchange (ETDEWEB)

Lopez, Soledad [CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville (Spain); Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville (Spain); Gomez, Enrique [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Torres, Maria J. [Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Pozo, David [CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville (Spain); Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville (Spain); Fernandez, Tahia D.; Ariza, Adriana [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Sanz, Maria L. [Department of Allergology and Clinical Immunology, University Clinic of Navarra, Pamplona (Spain); Blanca, Miguel [Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Mayorga, Cristobalina, E-mail: lina.mayorga@ibima.eu [Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain); Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga (Spain)

2015-11-01

The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.

Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam

Science.gov (United States)

Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

2015-01-01

The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples) were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX), 4 ng L-1 sulfadiazine (SDZ), 17 ng L-1 trimethoprim (TRIM), and 12 ng L-1 enrofloxacin (ENRO). These concentrations were lower than the predicted no effect concentrations (PNECs) and minimum inhibitory concentrations (MICs), suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from aquatic environment, yet the persistence of these antibiotics is of concern and might lead to chronic exposure of aquatic organisms as well as humans. PMID:26135396

The design of 3D scaffold for tissue engineering using automated scaffold design algorithm.

Science.gov (United States)

Mahmoud, Shahenda; Eldeib, Ayman; Samy, Sherif

2015-06-01

Several progresses have been introduced in the field of bone regenerative medicine. A new term tissue engineering (TE) was created. In TE, a highly porous artificial extracellular matrix or scaffold is required to accommodate cells and guide their growth in three dimensions. The design of scaffolds with desirable internal and external structure represents a challenge for TE. In this paper, we introduce a new method known as automated scaffold design (ASD) for designing a 3D scaffold with a minimum mismatches for its geometrical parameters. The method makes use of k-means clustering algorithm to separate the different tissues and hence decodes the defected bone portions. The segmented portions of different slices are registered to construct the 3D volume for the data. It also uses an isosurface rendering technique for 3D visualization of the scaffold and bones. It provides the ability to visualize the transplanted as well as the normal bone portions. The proposed system proves good performance in both the segmentation results and visualizations aspects.

Composite porous scaffold of PEG/PLA support improved bone matrix deposition in vitro compared to PLA-only scaffolds.

Science.gov (United States)

Bhaskar, Birru; Owen, Robert; Bahmaee, Hossein; Wally, Zena; Sreenivasa Rao, Parcha; Reilly, Gwendolen C

2018-05-01

Controllable pore size and architecture are essential properties for tissue-engineering scaffolds to support cell ingrowth colonization. To investigate the effect of polyethylene glycol (PEG) addition on porosity and bone-cell behavior, porous polylactic acid (PLA)-PEG scaffolds were developed with varied weight ratios of PLA-PEG (100/0, 90/10, 75/25) using solvent casting and porogen leaching. Sugar 200-300 µm in size was used as a porogen. To assess scaffold suitability for bone tissue engineering, MLO-A5 murine osteoblast cells were cultured and cell metabolic activity, alkaline phosphatase (ALP) activity and bone-matrix production determined using (alizarin red S staining for calcium and direct red 80 staining for collagen). It was found that metabolic activity was significantly higher over time on scaffolds containing PEG, ALP activity and mineralized matrix production were also significantly higher on scaffolds containing 25% PEG. Porous architecture and cell distribution and penetration into the scaffold were analyzed using SEM and confocal microscopy, revealing that inclusion of PEG increased pore interconnectivity and therefore cell ingrowth in comparison to pure PLA scaffolds. The results of this study confirmed that PLA-PEG porous scaffolds support mineralizing osteoblasts better than pure PLA scaffolds, indicating they have a high potential for use in bone tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1334-1340, 2018. © 2018 Wiley Periodicals, Inc.

Neuronal Networks on Nanocellulose Scaffolds.

Science.gov (United States)

Jonsson, Malin; Brackmann, Christian; Puchades, Maja; Brattås, Karoline; Ewing, Andrew; Gatenholm, Paul; Enejder, Annika

2015-11-01

Proliferation, integration, and neurite extension of PC12 cells, a widely used culture model for cholinergic neurons, were studied in nanocellulose scaffolds biosynthesized by Gluconacetobacter xylinus to allow a three-dimensional (3D) extension of neurites better mimicking neuronal networks in tissue. The interaction with control scaffolds was compared with cationized nanocellulose (trimethyl ammonium betahydroxy propyl [TMAHP] cellulose) to investigate the impact of surface charges on the cell interaction mechanisms. Furthermore, coatings with extracellular matrix proteins (collagen, fibronectin, and laminin) were investigated to determine the importance of integrin-mediated cell attachment. Cell proliferation was evaluated by a cellular proliferation assay, while cell integration and neurite propagation were studied by simultaneous label-free Coherent anti-Stokes Raman Scattering and second harmonic generation microscopy, providing 3D images of PC12 cells and arrangement of nanocellulose fibrils, respectively. Cell attachment and proliferation were enhanced by TMAHP modification, but not by protein coating. Protein coating instead promoted active interaction between the cells and the scaffold, hence lateral cell migration and integration. Irrespective of surface modification, deepest cell integration measured was one to two cell layers, whereas neurites have a capacity to integrate deeper than the cell bodies in the scaffold due to their fine dimensions and amoeba-like migration pattern. Neurites with lengths of >50 μm were observed, successfully connecting individual cells and cell clusters. In conclusion, TMAHP-modified nanocellulose scaffolds promote initial cellular scaffold adhesion, which combined with additional cell-scaffold treatments enables further formation of 3D neuronal networks.

Use of Rat Estrus Serum for in Vitro Maturation of Bovine Oocytes

Directory of Open Access Journals (Sweden)

AR Rafati

2007-04-01

Full Text Available Introduction: Superovulation produces complications in some patients, so invitro maturation of oocytes is used to decrease or eliminate these complications and improve IVF. Moreover, IVM is used for different aspects of reproductive researches. Slaughterhouse ovaries are the main source of oocytes for IVM and IVF studies. Different media has been introduced and experimented for in vitro maturation of oocytes. Animal's serum at estrus stage contains different hormones and proteins which are essential for oocyte maturation. The aim of this study was to compare three culture media for in vitro maturation (IVM of bovine oocytes; 1(controlTCM-199, 2HCG and follicular fluid (FF and 3 antibiotic. Methods: Rat estrus serum (RSS or fetal bovine serum (FBS was added to control medium. Total of 1789 compact cumulus oocyte complexes (COCs were aspirated from ovaries of slaughtered animals. Oocytes were randomly cultured in mentioned media and incubated in 38.5◦c, 5% CO2 and 95% humidity for 24 hours. The maturation of oocytes was judged according to cumulus cell expansion or randomly orcein stained oocytes and observation of polar bodies. Results: The results showed that maturation rate was significantly higher in second and third group (90.2%, 78.7% as compared to the control group (p<0.001. There was no significant difference between second and third groups (90.2 % vs. 86.6%. Conclusion: RSS is as effective as FBS for IVM of bovine oocytes and can be used as an alternative.

Multilayer scaffolds in orthopaedic tissue engineering.

Science.gov (United States)

Atesok, Kivanc; Doral, M Nedim; Karlsson, Jon; Egol, Kenneth A; Jazrawi, Laith M; Coelho, Paulo G; Martinez, Amaury; Matsumoto, Tomoyuki; Owens, Brett D; Ochi, Mitsuo; Hurwitz, Shepard R; Atala, Anthony; Fu, Freddie H; Lu, Helen H; Rodeo, Scott A

2016-07-01

The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.

Titanate nanotube coatings on biodegradable photopolymer scaffolds

Energy Technology Data Exchange (ETDEWEB)

Beke, S., E-mail: szabolcs.beke@iit.it [Department of Nanophysics, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova (Italy); Kőrösi, L. [Department of Biotechnology, Nanophage Therapy Center, Enviroinvest Corporation, Kertváros u. 2, H-7632, Pécs (Hungary); Scarpellini, A. [Department of Nanochemistry, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova (Italy); Anjum, F.; Brandi, F. [Department of Nanophysics, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova (Italy)

2013-05-01

Rigid, biodegradable photopolymer scaffolds were coated with titanate nanotubes (TNTs) by using a spin-coating method. TNTs were synthesized by a hydrothermal process at 150 °C under 4.7 bar ambient pressure. The biodegradable photopolymer scaffolds were produced by mask-assisted excimer laser photocuring at 308 nm. For scaffold coating, a stable ethanolic TNT sol was prepared by a simple colloid chemical route without the use of any binding compounds or additives. Scanning electron microscopy along with elemental analysis revealed that the scaffolds were homogenously coated by TNTs. The developed TNT coating can further improve the surface geometry of fabricated scaffolds, and therefore it can further increase the cell adhesion. Highlights: ► Biodegradable scaffolds were produced by mask-assisted UV laser photocuring. ► Titanate nanotube deposition was carried out without binding compounds or additives. ► The titanate nanotube coating can further improve the surface geometry of scaffolds. ► These reproducible platforms will be of high importance for biological applications.

Antibiotics

Science.gov (United States)

Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

Construction and characterization of an electrospun tubular scaffold for small-diameter tissue-engineered vascular grafts: a scaffold membrane approach.

Science.gov (United States)

Hu, Jin-Jia; Chao, Wei-Chih; Lee, Pei-Yuan; Huang, Chih-Hao

2012-09-01

Based on a postulate that the microstructure of a scaffold can influence that of the resulting tissue and hence its mechanical behavior, we fabricated a small-diameter tubular scaffold (∼3 mm inner diameter) that has a microstructure similar to the arterial media using a scaffold membrane approach. Scaffold membranes that contain randomly oriented, moderately aligned, or highly aligned fibers were fabricated by collecting electrospun poly([epsilon]-caprolactone) fibers on a grounded rotating drum at three different drum rotation speeds (250, 1000, and 1500 rpm). Membranes of each type were wrapped around a small-diameter mandrel to form the tubular scaffolds. Particularly, the tubular scaffolds with three different off-axis fiber angles (30, 45, and 60 degree) were formed using membranes that contain aligned fibers. These scaffolds were subjected to biaxial mechanical testing to examine the effects of fiber directions as well as the distribution of fiber orientations on their mechanical properties. The circumferential elastic modulus of the tubular scaffold was closely related to the fiber directions; the larger the off-axis fiber angle the greater the circumferential elastic modulus. The distribution of fiber orientations, on the other hand, manifested itself in the mechanical behavior via the Poisson effect. Similar to cell sheet-based vascular tissue engineering, tubular cell-seeded constructs were prepared by wrapping cell-seeded scaffold membranes, alleviating the difficulty associated with cell seeding in electrospun scaffolds. Histology of the construct illustrated that cells were aligned to the fiber directions in the construct, demonstrating the potential to control the microstructure of tissue-engineered vascular grafts using the electrospun scaffold membrane. Copyright © 2012 Elsevier Ltd. All rights reserved.

Image-based characterization of foamed polymeric tissue scaffolds

International Nuclear Information System (INIS)

Mather, Melissa L; Morgan, Stephen P; Crowe, John A; White, Lisa J; Shakesheff, Kevin M; Tai, Hongyun; Howdle, Steven M; Kockenberger, Walter

2008-01-01

Tissue scaffolds are integral to many regenerative medicine therapies, providing suitable environments for tissue regeneration. In order to assess their suitability, methods to routinely and reproducibly characterize scaffolds are needed. Scaffold structures are typically complex, and thus their characterization is far from trivial. The work presented in this paper is centred on the application of the principles of scaffold characterization outlined in guidelines developed by ASTM International. Specifically, this work demonstrates the capabilities of different imaging modalities and analysis techniques used to characterize scaffolds fabricated from poly(lactic-co-glycolic acid) using supercritical carbon dioxide. Three structurally different scaffolds were used. The scaffolds were imaged using: scanning electron microscopy, micro x-ray computed tomography, magnetic resonance imaging and terahertz pulsed imaging. In each case two-dimensional images were obtained from which scaffold properties were determined using image processing. The findings of this work highlight how the chosen imaging modality and image-processing technique can influence the results of scaffold characterization. It is concluded that in order to obtain useful results from image-based scaffold characterization, an imaging methodology providing sufficient contrast and resolution must be used along with robust image segmentation methods to allow intercomparison of results

Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo.

Science.gov (United States)

Kim, Ju-Ang; Lim, Jiwon; Naren, Raja; Yun, Hui-Suk; Park, Eui Kyun

2016-10-15

Similar to calcium phosphates, magnesium phosphate (MgP) ceramics have been shown to be biocompatible and support favorable conditions for bone cells. Micropores below 25μm (MgP25), between 25 and 53μm (MgP53), or no micropores (MgP0) were introduced into MgP scaffolds using different sizes of an NaCl template. The porosities of MgP25 and MgP53 were found to be higher than that of MgP0 because of their micro-sized pores. Both in vitro and in vivo analysis showed that MgP scaffolds with high porosity promoted rapid biodegradation. Implantation of the MgP0, MgP25, and MgP53 scaffolds into rabbit calvarial defects (with 4- and 6-mm diameters) was assessed at two times points (4 and 8weeks), followed by analysis of bone regeneration. The micro-CT and histologic analyses of the 4-mm defect showed that the MgP25 and MgP53 scaffolds were degraded completely at 4weeks with simultaneous bone and marrow-like structure regeneration. For the 6-mm defect, a similar pattern of regeneration was observed. These results indicate that the rate of degradation is associated with bone regeneration. The MgP25 and MgP53 scaffold-implanted bone showed a better lamellar structure and enhanced calcification compared to the MgP0 scaffold because of their porosity and degradation rate. Tartrate-resistant acid phosphatase (TRAP) staining indicated that the newly formed bone was undergoing maturation and remodeling. Overall, these data suggest that the pore architecture of MgP ceramic scaffolds greatly influence bone formation and remodeling activities and thus should be considered in the design of new scaffolds for long-term bone tissue regeneration. The pore structural conditions of scaffold, including porosity, pore size, pore morphology, and pore interconnectivity affect cell ingrowth, mechanical properties and biodegradabilities, which are key components of scaffold in bone tissue regeneration. In this study, we designed hierarchical pore structure of the magnesium phosphate (Mg

Environmental pollution by antibiotics and by antibiotic resistance determinants

International Nuclear Information System (INIS)

Martinez, Jose Luis

2009-01-01

Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

Environmental pollution by antibiotics and by antibiotic resistance determinants

Energy Technology Data Exchange (ETDEWEB)

Martinez, Jose Luis, E-mail: jlmtnez@cnb.csic.e [Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Darwin 3, Cantoblanco, 28049 Madrid, and CIBERESP (Spain)

2009-11-15

Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

Porous magnesium-based scaffolds for tissue engineering

International Nuclear Information System (INIS)

Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Moharamzadeh, Keyvan; Boccaccini, Aldo R.; Tayebi, Lobat

2017-01-01

Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail. - Highlights: • A porous 3D material provides the required pathways for cells to grow, proliferate, and differentiate • Porous magnesium and Mg alloys could be used as load-bearing scaffolds • Porous magnesium and Mg alloys are good

Porous magnesium-based scaffolds for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Yazdimamaghani, Mostafa [School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States); Razavi, Mehdi [Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304 (United States); Vashaee, Daryoosh [Electrical and Computer Engineering Department, North Carolina State University, Raleigh, NC 27606 (United States); Moharamzadeh, Keyvan [School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield (United Kingdom); Marquette University School of Dentistry, Milwaukee, WI 53233 (United States); Boccaccini, Aldo R. [Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen (Germany); Tayebi, Lobat, E-mail: lobat.tayebi@marquette.edu [Marquette University School of Dentistry, Milwaukee, WI 53233 (United States)

2017-02-01

Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail. - Highlights: • A porous 3D material provides the required pathways for cells to grow, proliferate, and differentiate • Porous magnesium and Mg alloys could be used as load-bearing scaffolds • Porous magnesium and Mg alloys are good

Recombinant protein scaffolds for tissue engineering

International Nuclear Information System (INIS)

Werkmeister, Jerome A; Ramshaw, John A M

2012-01-01

New biological materials for tissue engineering are now being developed using common genetic engineering capabilities to clone and express a variety of genetic elements that allow cost-effective purification and scaffold fabrication from these recombinant proteins, peptides or from chimeric combinations of these. The field is limitless as long as the gene sequences are known. The utility is dependent on the ease, product yield and adaptability of these protein products to the biomedical field. The development of recombinant proteins as scaffolds, while still an emerging technology with respect to commercial products, is scientifically superior to current use of natural materials or synthetic polymer scaffolds, in terms of designing specific structures with desired degrees of biological complexities and motifs. In the field of tissue engineering, next generation scaffolds will be the key to directing appropriate tissue regeneration. The initial period of biodegradable synthetic scaffolds that provided shape and mechanical integrity, but no biological information, is phasing out. The era of protein scaffolds offers distinct advantages, particularly with the combination of powerful tools of molecular biology. These include, for example, the production of human proteins of uniform quality that are free of infectious agents and the ability to make suitable quantities of proteins that are found in low quantity or are hard to isolate from tissue. For the particular needs of tissue engineering scaffolds, fibrous proteins like collagens, elastin, silks and combinations of these offer further advantages of natural well-defined structural scaffolds as well as endless possibilities of controlling functionality by genetic manipulation. (topical review)

Peer scaffolding in an EFL writing classroom: An investigation of writing accuracy and scaffolding behaviors

Directory of Open Access Journals (Sweden)

Parastou Gholami Pasand

2017-09-01

Full Text Available Considering the tenets of Sociocultural Theory with its emphasis on co-construction of knowledge, L2 writing can be regarded as a co-writing practice whereby assistance is provided to struggling writers. To date, most studies have dealt with peer scaffolding in the revision phase of writing, as such planning and drafting are remained untouched. The present study examines the impact of peer scaffolding on writing accuracy of a group of intermediate EFL learners, and explores scaffolding behaviors employed by them in planning and drafting phases of writing. To these ends, 40 freshmen majoring in English Language and Literature in the University of Guilan were randomly divided into a control group and an experimental group consisting of dyads in which a competent writer provided scaffolding to a less competent one using the process approach to writing. Results of independent samples t-tests revealed that learners in the experimental group produced more accurate essays. Microgenetic analysis of one dyad’s talks showed that scaffolding behaviors used in planning and drafting phases of writing were more or less the same as those identified in the revision phase. These findings can be used to inform peer intervention in L2 writing classes, and assist L2 learners in conducting successful peer scaffolding in the planning and drafting phases of writing.

Biodegradable Polymer-Based Scaffolds for Bone Tissue Engineering

CERN Document Server

Sultana, Naznin

2013-01-01

This book addresses the principles, methods and applications of biodegradable polymer based scaffolds for bone tissue engineering. The general principle of bone tissue engineering is reviewed and the traditional and novel scaffolding materials, their properties and scaffold fabrication techniques are explored. By acting as temporary synthetic extracellular matrices for cell accommodation, proliferation, and differentiation, scaffolds play a pivotal role in tissue engineering. This book does not only provide the comprehensive summary of the current trends in scaffolding design but also presents the new trends and directions for scaffold development for the ever expanding tissue engineering applications.

Platelet lysate embedded scaffolds for skin regeneration.

Science.gov (United States)

Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Ferrari, Franca; Mori, Michela; Cervio, Marila; Riva, Federica; Liakos, Ioannis; Athanassiou, Athanassia; Saporito, Francesca; Marini, Lara; Caramella, Carla

2015-04-01

The work presents the development of acellular scaffolds extemporaneously embedded with platelet lysate (PL), as an innovative approach in the field of tissue regeneration/reparation. PL embedded scaffolds should have a tridimensional architecture to support cell migration and growth, in order to restore skin integrity. For this reason, chondroitin sulfate (CS) was associated with sodium alginate (SA) to prepare highly porous systems. The developed scaffolds were characterized for chemical stability to γ-radiation, morphology, hydration and mechanical properties. Moreover, the capability of fibroblasts and endothelial cells to populate the scaffold was evaluated by means of proliferation test 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and confocal laser scanning microscopy study. The scaffolds, not altered by sterilization, were characterized by limited swelling and high flexibility, by foam-like structure with bubbles that formed a high surface area and irregular texture suitable for cell adhesion. Cell growth and scaffold population were evident on the bubble surface, where the cells appeared anchored to the scaffold structure. Scaffold network based on CS and SA demonstrated to be an effective support to enhance and to allow fibroblasts and endothelial cells (human umbilical vein endothelial cells, HUVEC) adhesion and proliferation. In particular, it could be hypothesized that cell adhesion was facilitated by the synergic effect of PL and CS. Although further in vivo evaluation is needed, on the basis of in vitro results, PL embedded scaffolds seem promising systems for skin wound healing.

Semiotic Scaffolding in Mathematics

DEFF Research Database (Denmark)

Johansen, Mikkel Willum; Misfeldt, Morten

2015-01-01

This paper investigates the notion of semiotic scaffolding in relation to mathematics by considering its influence on mathematical activities, and on the evolution of mathematics as a research field. We will do this by analyzing the role different representational forms play in mathematical...... cognition, and more broadly on mathematical activities. In the main part of the paper, we will present and analyze three different cases. For the first case, we investigate the semiotic scaffolding involved in pencil and paper multiplication. For the second case, we investigate how the development of new...... in both mathematical cognition and in the development of mathematics itself, but mathematical cognition cannot itself be reduced to the use of semiotic scaffolding....

Fluorescent composite scaffolds made of nanodiamonds/polycaprolactone

Science.gov (United States)

Cao, Li; Hou, Yanwen; Lafdi, Khalid; Urmey, Kirk

2015-11-01

Polycaprolactone (PCL) has been widely studied for biological applications. Biodegradable PCL fibrous scaffold can work as an appropriate substrate for tissue regeneration. In this letter, fluorescent nanodiamonds (FNDs) were prepared after surface passivation with octadecylamine. The FNDs were then mixed with PCL polymer and subsequently electrospun into FNDs/PCL fibrous scaffolds. The obtained scaffolds not only exhibited photoluminescence, but also showed reinforced mechanical strength. Toxicity study indicated FNDs/PCL scaffolds were nontoxic. This biocompatible fluorescent composite fibrous scaffold can support in vitro cell growth and also has the potential to act as an optical probe for tissue engineering application in vitro and in vivo.

Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig.

Science.gov (United States)

Hsieh, Yi-Ho; Shen, Bo-Yuan; Wang, Yao-Horng; Lin, Bojain; Lee, Hung-Maan; Hsieh, Ming-Fa

2018-04-09

Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM) layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-β1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT). The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-β1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.

Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig

Directory of Open Access Journals (Sweden)

Yi-Ho Hsieh

2018-04-01

Full Text Available Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol-block-poly(ε-caprolactone (mPEG-PCL and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-β1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT. The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-β1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.

Calcium channel-dependent molecular maturation of photoreceptor synapses.

Directory of Open Access Journals (Sweden)

Nawal Zabouri

Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

Calcium channel-dependent molecular maturation of photoreceptor synapses.

Science.gov (United States)

Zabouri, Nawal; Haverkamp, Silke

2013-01-01

Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(α(1F)) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V)1.4(α(1F)) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V)1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V)1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation

Energy Technology Data Exchange (ETDEWEB)

Lokareddy, Ravi K.; Sankhala, Rajeshwer S.; Roy, Ankoor; Afonine, Pavel V.; Motwani, Tina; Teschke, Carolyn M.; Parent, Kristin N.; Cingolani, Gino (Rutgers); (LBNL); (Connecticut); (TJU); (MSU)

2017-01-30

Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or ‘procapsid’) built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinity for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of ‘Headful Packaging’ is a DNA-dependent symmetrization of portal protein.

Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation

Science.gov (United States)

Lokareddy, Ravi K.; Sankhala, Rajeshwer S.; Roy, Ankoor; Afonine, Pavel V.; Motwani, Tina; Teschke, Carolyn M.; Parent, Kristin N.; Cingolani, Gino

2017-01-01

Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or ‘procapsid') built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinity for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of ‘Headful Packaging' is a DNA-dependent symmetrization of portal protein. PMID:28134243

Novel biodegradable porous scaffold applied to skin regeneration.

Science.gov (United States)

Wang, Hui-Min; Chou, Yi-Ting; Wen, Zhi-Hong; Wang, Chau-Zen; Wang, Zhao-Ren; Chen, Chun-Hong; Ho, Mei-Ling

2013-01-01

Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.

Novel biodegradable porous scaffold applied to skin regeneration.

Directory of Open Access Journals (Sweden)

Hui-Min Wang

Full Text Available Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.

[Strategies to choose scaffold materials for tissue engineering].

Science.gov (United States)

Gao, Qingdong; Zhu, Xulong; Xiang, Junxi; Lü, Yi; Li, Jianhui

2016-02-01

Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(ε-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which

Nano-ceramic composite scaffolds for bioreactor-based bone engineering.

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Lv, Qing; Deng, Meng; Ulery, Bret D; Nair, Lakshmi S; Laurencin, Cato T

2013-08-01

Composites of biodegradable polymers and bioactive ceramics are candidates for tissue-engineered scaffolds that closely match the properties of bone. We previously developed a porous, three-dimensional poly (D,L-lactide-co-glycolide) (PLAGA)/nanohydroxyapatite (n-HA) scaffold as a potential bone tissue engineering matrix suitable for high-aspect ratio vessel (HARV) bioreactor applications. However, the physical and cellular properties of this scaffold are unknown. The present study aims to evaluate the effect of n-HA in modulating PLAGA scaffold properties and human mesenchymal stem cell (HMSC) responses in a HARV bioreactor. By comparing PLAGA/n-HA and PLAGA scaffolds, we asked whether incorporation of n-HA (1) accelerates scaffold degradation and compromises mechanical integrity; (2) promotes HMSC proliferation and differentiation; and (3) enhances HMSC mineralization when cultured in HARV bioreactors. PLAGA/n-HA scaffolds (total number = 48) were loaded into HARV bioreactors for 6 weeks and monitored for mass, molecular weight, mechanical, and morphological changes. HMSCs were seeded on PLAGA/n-HA scaffolds (total number = 38) and cultured in HARV bioreactors for 28 days. Cell migration, proliferation, osteogenic differentiation, and mineralization were characterized at four selected time points. The same amount of PLAGA scaffolds were used as controls. The incorporation of n-HA did not alter the scaffold degradation pattern. PLAGA/n-HA scaffolds maintained their mechanical integrity throughout the 6 weeks in the dynamic culture environment. HMSCs seeded on PLAGA/n-HA scaffolds showed elevated proliferation, expression of osteogenic phenotypic markers, and mineral deposition as compared with cells seeded on PLAGA scaffolds. HMSCs migrated into the scaffold center with nearly uniform cell and extracellular matrix distribution in the scaffold interior. The combination of PLAGA/n-HA scaffolds with HMSCs in HARV bioreactors may allow for the generation of engineered

A radiopaque electrospun scaffold for engineering fibrous musculoskeletal tissues: Scaffold characterization and in vivo applications.

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Martin, John T; Milby, Andrew H; Ikuta, Kensuke; Poudel, Subash; Pfeifer, Christian G; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2015-10-01

Tissue engineering strategies have emerged in response to the growing prevalence of chronic musculoskeletal conditions, with many of these regenerative methods currently being evaluated in translational animal models. Engineered replacements for fibrous tissues such as the meniscus, annulus fibrosus, tendons, and ligaments are subjected to challenging physiologic loads, and are difficult to track in vivo using standard techniques. The diagnosis and treatment of musculoskeletal conditions depends heavily on radiographic assessment, and a number of currently available implants utilize radiopaque markers to facilitate in vivo imaging. In this study, we developed a nanofibrous scaffold in which individual fibers included radiopaque nanoparticles. Inclusion of radiopaque particles increased the tensile modulus of the scaffold and imparted radiation attenuation within the range of cortical bone. When scaffolds were seeded with bovine mesenchymal stem cells in vitro, there was no change in cell proliferation and no evidence of promiscuous conversion to an osteogenic phenotype. Scaffolds were implanted ex vivo in a model of a meniscal tear in a bovine joint and in vivo in a model of total disc replacement in the rat coccygeal spine (tail), and were visualized via fluoroscopy and microcomputed tomography. In the disc replacement model, histological analysis at 4 weeks showed that the scaffold was biocompatible and supported the deposition of fibrous tissue in vivo. Nanofibrous scaffolds that include radiopaque nanoparticles provide a biocompatible template with sufficient radiopacity for in vivo visualization in both small and large animal models. This radiopacity may facilitate image-guided implantation and non-invasive long-term evaluation of scaffold location and performance. The healing capacity of fibrous musculoskeletal tissues is limited, and injury or degeneration of these tissues compromises the standard of living of millions in the US. Tissue engineering repair

Development of nanofibrous scaffolds containing gum tragacanth/poly (ε-caprolactone) for application as skin scaffolds

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Ranjbar-Mohammadi, Marziyeh [Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Bahrami, S. Hajir, E-mail: hajirb@aut.ac.ir [Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Center for excellence Modern Textile Characterization, Tehran (Iran, Islamic Republic of)

2015-03-01

Outstanding wound healing activity of gum tragacanth (GT) and higher mechanical strength of poly (ε-caprolactone) (PCL) may produce an excellent nanofibrous patch for either skin tissue engineering or wound dressing application. PCL/GT scaffold containing different concentrations of PCL with different blend ratios of GT/PCL was produced using 90% acetic acid as solvent. The results demonstrated that the PCL/GT (3:1.5) with PCL concentration of 20% (w/v) produced nanofibers with proper morphology. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were utilized to characterize the nanofibers. Surface wettability, functional groups analysis, porosity and tensile properties of nanofibers were evaluated. Morphological characterization showed that the addition of GT to PCL solution results in decreasing the average diameter of the PCL/GT nanofibers. However, the hydrophilicity increased in the PCL/GT nanofibers. Slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. PCL/GT nanofibers were used for in vitro cell culture of human fibroblast cell lines AGO and NIH 3T3 fibroblast cells. MTT assay and SEM results showed that the biocomposite PCL/GT mats enhanced the fibroblast adhesion and proliferation compared to PCL scaffolds. The antibacterial activity of PCL/GT and GT nanofibers against Staphylococcus aureus and Pseudomonas aeruginosa was also examined. - Highlights: • A new skin tissue engineering scaffold from poly (ε-caprolactone) (PCL) and gum tragacanth (GT) has been developed. • These scaffolds might be an effectual simulator of the structure and composition of native skin. • Very slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. • Biodegradation, water uptake and hydrophilicity properties of these scaffolds showed that produced scaffolds were adherent. • The electrospun PCL/GT scaffold can promote the skin regeneration of full

Development of nanofibrous scaffolds containing gum tragacanth/poly (ε-caprolactone) for application as skin scaffolds

International Nuclear Information System (INIS)

Ranjbar-Mohammadi, Marziyeh; Bahrami, S. Hajir

2015-01-01

Outstanding wound healing activity of gum tragacanth (GT) and higher mechanical strength of poly (ε-caprolactone) (PCL) may produce an excellent nanofibrous patch for either skin tissue engineering or wound dressing application. PCL/GT scaffold containing different concentrations of PCL with different blend ratios of GT/PCL was produced using 90% acetic acid as solvent. The results demonstrated that the PCL/GT (3:1.5) with PCL concentration of 20% (w/v) produced nanofibers with proper morphology. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were utilized to characterize the nanofibers. Surface wettability, functional groups analysis, porosity and tensile properties of nanofibers were evaluated. Morphological characterization showed that the addition of GT to PCL solution results in decreasing the average diameter of the PCL/GT nanofibers. However, the hydrophilicity increased in the PCL/GT nanofibers. Slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. PCL/GT nanofibers were used for in vitro cell culture of human fibroblast cell lines AGO and NIH 3T3 fibroblast cells. MTT assay and SEM results showed that the biocomposite PCL/GT mats enhanced the fibroblast adhesion and proliferation compared to PCL scaffolds. The antibacterial activity of PCL/GT and GT nanofibers against Staphylococcus aureus and Pseudomonas aeruginosa was also examined. - Highlights: • A new skin tissue engineering scaffold from poly (ε-caprolactone) (PCL) and gum tragacanth (GT) has been developed. • These scaffolds might be an effectual simulator of the structure and composition of native skin. • Very slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. • Biodegradation, water uptake and hydrophilicity properties of these scaffolds showed that produced scaffolds were adherent. • The electrospun PCL/GT scaffold can promote the skin regeneration of full

Polycaprolactone nanofiber interspersed collagen type-I scaffold for bone regeneration: a unique injectable osteogenic scaffold

International Nuclear Information System (INIS)

Baylan, Nuray; Ditto, Maggie; Lawrence, Joseph G; Yildirim-Ayan, Eda; Bhat, Samerna; Lecka-Czernik, Beata

2013-01-01

There is an increasing demand for an injectable cell coupled three-dimensional (3D) scaffold to be used as bone fracture augmentation material. To address this demand, a novel injectable osteogenic scaffold called PN-COL was developed using cells, a natural polymer (collagen type-I), and a synthetic polymer (polycaprolactone (PCL)). The injectable nanofibrous PN-COL is created by interspersing PCL nanofibers within pre-osteoblast cell embedded collagen type-I. This simple yet novel and powerful approach provides a great benefit as an injectable bone scaffold over other non-living bone fracture stabilization polymers, such as polymethylmethacrylate and calcium content resin-based materials. The advantages of injectability and the biomimicry of collagen was coupled with the structural support of PCL nanofibers, to create cell encapsulated injectable 3D bone scaffolds with intricate porous internal architecture and high osteoconductivity. The effects of PCL nanofiber inclusion within the cell encapsulated collagen matrix has been evaluated for scaffold size retention and osteocompatibility, as well as for MC3T3-E1 cells osteogenic activity. The structural analysis of novel bioactive material proved that the material is chemically stable enough in an aqueous solution for an extended period of time without using crosslinking reagents, but it is also viscous enough to be injected through a syringe needle. Data from long-term in vitro proliferation and differentiation data suggests that novel PN-COL scaffolds promote the osteoblast proliferation, phenotype expression, and formation of mineralized matrix. This study demonstrates for the first time the feasibility of creating a structurally competent, injectable, cell embedded bone tissue scaffold. Furthermore, the results demonstrate the advantages of mimicking the hierarchical architecture of native bone with nano- and micro-size formation through introducing PCL nanofibers within macron-size collagen fibers and in

BESST--efficient scaffolding of large fragmented assemblies.

Science.gov (United States)

Sahlin, Kristoffer; Vezzi, Francesco; Nystedt, Björn; Lundeberg, Joakim; Arvestad, Lars

2014-08-15

The use of short reads from High Throughput Sequencing (HTS) techniques is now commonplace in de novo assembly. Yet, obtaining contiguous assemblies from short reads is challenging, thus making scaffolding an important step in the assembly pipeline. Different algorithms have been proposed but many of them use the number of read pairs supporting a linking of two contigs as an indicator of reliability. This reasoning is intuitive, but fails to account for variation in link count due to contig features.We have also noted that published scaffolders are only evaluated on small datasets using output from only one assembler. Two issues arise from this. Firstly, some of the available tools are not well suited for complex genomes. Secondly, these evaluations provide little support for inferring a software's general performance. We propose a new algorithm, implemented in a tool called BESST, which can scaffold genomes of all sizes and complexities and was used to scaffold the genome of P. abies (20 Gbp). We performed a comprehensive comparison of BESST against the most popular stand-alone scaffolders on a large variety of datasets. Our results confirm that some of the popular scaffolders are not practical to run on complex datasets. Furthermore, no single stand-alone scaffolder outperforms the others on all datasets. However, BESST fares favorably to the other tested scaffolders on GAGE datasets and, moreover, outperforms the other methods when library insert size distribution is wide. We conclude from our results that information sources other than the quantity of links, as is commonly used, can provide useful information about genome structure when scaffolding.

[Three-dimensional parallel collagen scaffold promotes tendon extracellular matrix formation].

Science.gov (United States)

Zheng, Zefeng; Shen, Weiliang; Le, Huihui; Dai, Xuesong; Ouyang, Hongwei; Chen, Weishan

2016-03-01

To investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells. Parallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation. Parallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder. Parallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing.

Antibiotics as CECs: An Overview of the Hazards Posed by Antibiotics and Antibiotic Resistance

Directory of Open Access Journals (Sweden)

Geoffrey Ivan Scott

2016-04-01

Full Text Available ABSTRACTMonitoring programs have traditionally monitored legacy contaminants but are shifting focus to Contaminants of Emerging Concern (CECs. CECs present many challenges for monitoring and assessment, because measurement methods don't always exist nor have toxicological studies been fully conducted to place results in proper context. Also some CECs affect metabolic pathways to produce adverse outcomes that are not assessed through traditional toxicological evaluations. Antibiotics are CECs that pose significant environmental risks including development of both toxic effects at high doses and antibiotic resistance at doses well below the Minimum Inhibitory Concentration (MIC which kill bacteria and have been found in nearly half of all sites monitored in the US. Antimicrobial resistance has generally been attributed to the use of antibiotics in medicine for humans and livestock as well as aquaculture operations. The objective of this study was to assess the extent and magnitude of antibiotics in the environment and estimate their potential hazards in the environment. Antibiotics concentrations were measured in a number of monitoring studies which included Waste Water Treatment Plants (WWTP effluent, surface waters, sediments and biota. A number of studies reported levels of Antibiotic Resistant Microbes (ARM in surface waters and some studies found specific ARM genes (e.g. the blaM-1 gene in E. coli which may pose additional environmental risk. High levels of this gene were found to survive WWTP disinfection and accumulated in sediment at levels 100-1000 times higher than in the sewerage effluent, posing potential risks for gene transfer to other bacteria.in aquatic and marine ecosystems. Antibiotic risk assessment approaches were developed based on the use of MICs and MIC Ratios [High (Antibiotic Resistant/Low (Antibiotic Sensitive MIC] for each antibiotic indicating the range of bacterial adaptability to each antibiotic to help define the No

The multifaceted roles of antibiotics and antibiotic resistance in nature

Directory of Open Access Journals (Sweden)

Saswati eSengupta

2013-03-01

Full Text Available Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic-resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic-resistance in pathogens. In the natural milieu, antibiotics are often found to be present in subinhibitory concentrations acting as signalling molecules supporting quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host-parasite interactions (e.g., phagocytosis, adherence to the target cell and so on. The evolutionary and ecological aspects of antibiotics and antibiotic-resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behaviour of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and genes that confer resistance to antibiotics in

Inverse Opal Scaffolds and Their Biomedical Applications.

Science.gov (United States)

Zhang, Yu Shrike; Zhu, Chunlei; Xia, Younan

2017-09-01

Three-dimensional porous scaffolds play a pivotal role in tissue engineering and regenerative medicine by functioning as biomimetic substrates to manipulate cellular behaviors. While many techniques have been developed to fabricate porous scaffolds, most of them rely on stochastic processes that typically result in scaffolds with pores uncontrolled in terms of size, structure, and interconnectivity, greatly limiting their use in tissue regeneration. Inverse opal scaffolds, in contrast, possess uniform pores inheriting from the template comprised of a closely packed lattice of monodispersed microspheres. The key parameters of such scaffolds, including architecture, pore structure, porosity, and interconnectivity, can all be made uniform across the same sample and among different samples. In conjunction with a tight control over pore sizes, inverse opal scaffolds have found widespread use in biomedical applications. In this review, we provide a detailed discussion on this new class of advanced materials. After a brief introduction to their history and fabrication, we highlight the unique advantages of inverse opal scaffolds over their non-uniform counterparts. We then showcase their broad applications in tissue engineering and regenerative medicine, followed by a summary and perspective on future directions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam.

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Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

2015-01-01

The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples) were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX), 4 ng L-1 sulfadiazine (SDZ), 17 ng L-1 trimethoprim (TRIM), and 12 ng L-1 enrofloxacin (ENRO). These concentrations were lower than the predicted no effect concentrations (PNECs) and minimum inhibitory concentrations (MICs), suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from antibiotics TRIM was the most persistent in water systems. TRIM was not susceptible to photodegradation, while the dissipation of ENRO and SDZ was influenced by photolysis. The recorded dissipation models gave good predictions of the occurrence and concentrations of TRIM, ENRO and SDZ in surface water. In summary, the currently measured concentrations of the investigated antibiotics are unlikely to cause immediate risks to the aquatic environment, yet the persistence of these antibiotics is of concern and might lead to

Bio-functionalized PCL nanofibrous scaffolds for nerve tissue engineering

International Nuclear Information System (INIS)

Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P.; Morshed, Mohammad; Nasr-Esfahani, Mohammad Hossein; Ramakrishna, S.

2010-01-01

Surface properties of scaffolds such as hydrophilicity and the presence of functional groups on the surface of scaffolds play a key role in cell adhesion, proliferation and migration. Different modification methods for hydrophilicity improvement and introduction of functional groups on the surface of scaffolds have been carried out on synthetic biodegradable polymers, for tissue engineering applications. In this study, alkaline hydrolysis of poly (ε-caprolactone) (PCL) nanofibrous scaffolds was carried out for different time periods (1 h, 4 h and 12 h) to increase the hydrophilicity of the scaffolds. The formation of reactive groups resulting from alkaline hydrolysis provides opportunities for further surface functionalization of PCL nanofibrous scaffolds. Matrigel was attached covalently on the surface of an optimized 4 h hydrolyzed PCL nanofibrous scaffolds and additionally the fabrication of blended PCL/matrigel nanofibrous scaffolds was carried out. Chemical and mechanical characterization of nanofibrous scaffolds were evaluated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, contact angle, scanning electron microscopy (SEM) and tensile measurement. In vitro cell adhesion and proliferation study was carried out after seeding nerve precursor cells (NPCs) on different scaffolds. Results of cell proliferation assay and SEM studies showed that the covalently functionalized PCL/matrigel nanofibrous scaffolds promote the proliferation and neurite outgrowth of NPCs compared to PCL and hydrolyzed PCL nanofibrous scaffolds, providing suitable substrates for nerve tissue engineering.

Selection of antibiotic resistance at very low antibiotic concentrations.

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Sandegren, Linus

2014-05-01

Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

Science.gov (United States)

Inzana, J A; Trombetta, R P; Schwarz, E M; Kates, S L; Awad, H A

2015-11-04

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection

Directory of Open Access Journals (Sweden)

JA Inzana

2015-11-01

Full Text Available Surgical implant-associated bone infections (osteomyelitis have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate (PMMA bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS by three-dimensional (3D printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

Spiral-structured, nanofibrous, 3D scaffolds for bone tissue engineering.

Science.gov (United States)

Wang, Junping; Valmikinathan, Chandra M; Liu, Wei; Laurencin, Cato T; Yu, Xiaojun

2010-05-01

Polymeric nanofiber matrices have already been widely used in tissue engineering. However, the fabrication of nanofibers into complex three-dimensional (3D) structures is restricted due to current manufacturing techniques. To overcome this limitation, we have incorporated nanofibers onto spiral-structured 3D scaffolds made of poly (epsilon-caprolactone) (PCL). The spiral structure with open geometries, large surface areas, and porosity will be helpful for improving nutrient transport and cell penetration into the scaffolds, which are otherwise limited in conventional tissue-engineered scaffolds for large bone defects repair. To investigate the effect of structure and fiber coating on the performance of the scaffolds, three groups of scaffolds including cylindrical PCL scaffolds, spiral PCL scaffolds (without fiber coating), and spiral-structured fibrous PCL scaffolds (with fiber coating) have been prepared. The morphology, porosity, and mechanical properties of the scaffolds have been characterized. Furthermore, human osteoblast cells are seeded on these scaffolds, and the cell attachment, proliferation, differentiation, and mineralized matrix deposition on the scaffolds are evaluated. The results indicated that the spiral scaffolds possess porosities within the range of human trabecular bone and an appropriate pore structure for cell growth, and significantly lower compressive modulus and strength than cylindrical scaffolds. When compared with the cylindrical scaffolds, the spiral-structured scaffolds demonstrated enhanced cell proliferation, differentiation, and mineralization and allowed better cellular growth and penetration. The incorporation of nanofibers onto spiral scaffolds further enhanced cell attachment, proliferation, and differentiation. These studies suggest that spiral-structured nanofibrous scaffolds may serve as promising alternatives for bone tissue engineering applications. Copyright 2009 Wiley Periodicals, Inc.

Preparation of bioactive porous HA/PCL composite scaffolds

Energy Technology Data Exchange (ETDEWEB)

Zhao, J.; Guo, L.Y.; Yang, X.B. [Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Weng, J. [Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)], E-mail: jweng@swjtu.cn

2008-12-30

Porous hydroxyapatite (HA) bioceramic scaffold has been widely attracted the attention to act as a three-dimensional (3D) template for cell adhesion, proliferation, differentiation and thus promoting bone and cartilage regeneration because of its osteoinduction. However, the porous bioceramic scaffold is fragile so that it is not suitable to be applied in clinic for bone repair or replacement. Therefore, it is significant to improve the mechanical property of porous HA bioceramics while the interconnected structure is maintained for tissue ingrowth in vivo. In the present research, a porous composite scaffold composed of HA scaffold and polycaprolactone (PCL) lining was fabricated by the method of polymer impregnating to produce HA scaffold coated with PCL lining. Subsequently, the composite scaffolds were deposited with biomimetic coating for improving the bioactivity. The HA/PCL composite scaffolds with improved mechanical property and bioactivity is expected to be a promising bone substitute in tissue engineering applications.

Polyelectrolyte-complex nanostructured fibrous scaffolds for tissue engineering

International Nuclear Information System (INIS)

Verma, Devendra; Katti, Kalpana S.; Katti, Dinesh R.

2009-01-01

In the current work, polyelectrolyte complex (PEC) fibrous scaffolds for tissue engineering have been synthesized and a mechanism of their formation has been investigated. The scaffolds are synthesized using polygalacturonic acid and chitosan using the freeze drying methodology. Highly interconnected pores of sizes in the range of 5-20 μm are observed in the scaffolds. The thickness of the fibers was found to be in the range of 1-2 μm. Individual fibers have a nanogranular structure as observed using AFM imaging. In these scaffolds, PEC nanoparticles assemble together at the interface of ice crystals during freeze drying process. Further investigation shows that the freezing temperature and concentration have a remarkable effect on structure of scaffolds. Biocompatibility studies show that scaffold containing chitosan, polygalacturonic acid and hydroxyapatite promotes cell adhesion and proliferation. On the other hand, cells on scaffolds fabricated without hydroxyapatite nanoparticles showed poor adhesion.

Preparation of bioactive porous HA/PCL composite scaffolds

International Nuclear Information System (INIS)

Zhao, J.; Guo, L.Y.; Yang, X.B.; Weng, J.

2008-01-01

Porous hydroxyapatite (HA) bioceramic scaffold has been widely attracted the attention to act as a three-dimensional (3D) template for cell adhesion, proliferation, differentiation and thus promoting bone and cartilage regeneration because of its osteoinduction. However, the porous bioceramic scaffold is fragile so that it is not suitable to be applied in clinic for bone repair or replacement. Therefore, it is significant to improve the mechanical property of porous HA bioceramics while the interconnected structure is maintained for tissue ingrowth in vivo. In the present research, a porous composite scaffold composed of HA scaffold and polycaprolactone (PCL) lining was fabricated by the method of polymer impregnating to produce HA scaffold coated with PCL lining. Subsequently, the composite scaffolds were deposited with biomimetic coating for improving the bioactivity. The HA/PCL composite scaffolds with improved mechanical property and bioactivity is expected to be a promising bone substitute in tissue engineering applications

Correlation between dental maturity and cervical vertebral maturity.

Science.gov (United States)

Chen, Jianwei; Hu, Haikun; Guo, Jing; Liu, Zeping; Liu, Renkai; Li, Fan; Zou, Shujuan

2010-12-01

The aim of this study was to investigate the association between dental and skeletal maturity. Digital panoramic radiographs and lateral skull cephalograms of 302 patients (134 boys and 168 girls, ranging from 8 to 16 years of age) were examined. Dental maturity was assessed by calcification stages of the mandibular canines, first and second premolars, and second molars, whereas skeletal maturity was estimated by the cervical vertebral maturation (CVM) stages. The Spearman rank-order correlation coefficient was used to measure the association between CVM stage and dental calcification stage of individual teeth. The mean chronologic age of girls was significantly lower than that of boys in each CVM stage. The Spearman rank-order correlation coefficients between dental maturity and cervical vertebral maturity ranged from 0.391 to 0.582 for girls and from 0.464 to 0.496 for boys (P cervical vertebral maturation stage. The development of the mandibular second molar in females and that of the mandibular canine in males had the strongest correlations with cervical vertebral maturity. Therefore, it is practical to consider the relationship between dental and skeletal maturity when planning orthodontic treatment. Copyright © 2010 Mosby, Inc. All rights reserved.

Selection of antibiotic resistance at very low antibiotic concentrations

OpenAIRE

Sandegren, Linus

2014-01-01

Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are fou...

Biomimetic nanoclay scaffolds for bone tissue engineering

Science.gov (United States)

Ambre, Avinash Harishchandra

Tissue engineering offers a significant potential alternative to conventional methods for rectifying tissue defects by evoking natural regeneration process via interactions between cells and 3D porous scaffolds. Imparting adequate mechanical properties to biodegradable scaffolds for bone tissue engineering is an important challenge and extends from molecular to macroscale. This work focuses on the use of sodium montmorillonite (Na-MMT) to design polymer composite scaffolds having enhanced mechanical properties along with multiple interdependent properties. Materials design beginning at the molecular level was used in which Na-MMT clay was modified with three different unnatural amino acids and further characterized using Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD). Based on improved bicompatibility with human osteoblasts (bone cells) and intermediate increase in d-spacing of MMT clay (shown by XRD), 5-aminovaleric acid modified clay was further used to prepare biopolymer (chitosan-polygalacturonic acid complex) scaffolds. Osteoblast proliferation in biopolymer scaffolds containing 5-aminovaleric acid modified clay was similar to biopolymer scaffolds containing hydroxyapatite (HAP). A novel process based on biomineralization in bone was designed to prepare 5-aminovaleric acid modified clay capable of imparting multiple properties to the scaffolds. Bone-like apatite was mineralized in modified clay and a novel nanoclay-HAP hybrid (in situ HAPclay) was obtained. FTIR spectroscopy indicated a molecular level organic-inorganic association between the intercalated 5-aminovaleric acid and mineralized HAP. Osteoblasts formed clusters on biopolymer composite films prepared with different weight percent compositions of in situ HAPclay. Human MSCs formed mineralized nodules on composite films and mineralized extracellular matrix (ECM) in composite scaffolds without the use of osteogenic supplements. Polycaprolactone (PCL), a synthetic polymer, was

Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

OpenAIRE

Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

2014-01-01

It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really ...

Anisotropic silk fibroin/gelatin scaffolds from unidirectional freezing

Energy Technology Data Exchange (ETDEWEB)

Asuncion, Maria Christine Tankeh, E-mail: christine.asuncion@u.nus.edu [National University of Singapore, Department of Biomedical Engineering (Singapore); Goh, James Cho-Hong [National University of Singapore, Department of Biomedical Engineering (Singapore); National University of Singapore, Department of Orthopedic Surgery (Singapore); Toh, Siew-Lok [National University of Singapore, Department of Biomedical Engineering (Singapore); National University of Singapore, Department of Mechanical Engineering (Singapore)

2016-10-01

Recent studies have underlined the importance of matching scaffold properties to the biological milieu. Tissue, and thus scaffold, anisotropy is one such property that is important yet sometimes overlooked. Methods that have been used to achieve anisotropic scaffolds present challenges such as complicated fabrication steps, harsh processing conditions and toxic chemicals involved. In this study, unidirectional freezing was employed to fabricate anisotropic silk fibroin/gelatin scaffolds in a simple and mild manner. Morphological, mechanical, chemical and cellular compatibility properties were investigated, as well as the effect of the addition of gelatin to certain properties of the scaffold. It was shown that scaffold properties were suitable for cell proliferation and that mesenchymal stem cells were able to align themselves along the directed fibers. The fabricated scaffolds present a platform that can be used for anisotropic tissue engineering applications such as cardiac patches. - Highlights: • Silk/gelatin scaffolds with unidirectional alignment were fabricated using a simple and scalable process • Presence of gelatin in silk resulted to lesser shrinkage, better water retention and improved cell proliferation. • Mesenchymal stem cells were shown to align themselves according to the fiber alignment.

Handling Time-dependent Variables : Antibiotics and Antibiotic Resistance

NARCIS (Netherlands)

Munoz-Price, L. Silvia; Frencken, Jos F.; Tarima, Sergey; Bonten, Marc

2016-01-01

Elucidating quantitative associations between antibiotic exposure and antibiotic resistance development is important. In the absence of randomized trials, observational studies are the next best alternative to derive such estimates. Yet, as antibiotics are prescribed for varying time periods,

Cell-derived matrix coatings for polymeric scaffolds.

Science.gov (United States)

Decaris, Martin L; Binder, Bernard Y; Soicher, Matthew A; Bhat, Archana; Leach, J Kent

2012-10-01

Cells in culture deposit a complex extracellular matrix that remains intact following decellularization and possesses the capacity to modulate cell phenotype. The direct application of such decellularized matrices (DMs) to 3D substrates is problematic, as transport issues influence the homogeneous deposition, decellularization, and modification of DM surface coatings. In an attempt to address this shortcoming, we hypothesized that DMs deposited by human mesenchymal stem cells (MSCs) could be transferred to the surface of polymeric scaffolds while maintaining their capacity to direct cell fate. The ability of the transferred DM (tDM)-coated scaffolds to enhance the osteogenic differentiation of undifferentiated and osteogenically induced MSCs under osteogenic conditions in vitro was confirmed. tDM-coated scaffolds increased MSC expression of osteogenic marker genes (BGLAP, IBSP) and intracellular alkaline phosphatase production. In addition, undifferentiated MSCs deposited significantly more calcium when seeded onto tDM-coated scaffolds compared with control scaffolds. MSC-seeded tDM-coated scaffolds subcutaneously implanted in nude rats displayed significantly higher blood vessel density after 2 weeks compared with cells on uncoated scaffolds, but we did not observe significant differences in mineral deposition after 8 weeks. These data demonstrate that DM-coatings produced in 2D culture can be successfully transferred to 3D substrates and retain their capacity to modulate cell phenotype.

Designer bFGF-incorporated D-form self-assembly peptide nanofiber scaffolds to promote bone repair

Energy Technology Data Exchange (ETDEWEB)

He, Bin, E-mail: binheing@163.com [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Ou, Yunsheng; Chen, Shuo; Zhao, Weikang; Zhou, Ao [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhao, Jinqiu [Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Li, Hong [School of Physical Science and Technology, Sichuan University, Chengdu 610000 (China); Jiang, Dianming [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Zhu, Yong, E-mail: 568731668@qq.com [Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China)

2017-05-01

D-Form and L-form peptide nanofiber scaffolds can spontaneously form stable β-sheet secondary structures and nanofiber hydrogel scaffolds, and hold some promise in hemostasis and wound healing. We report here on the synthetic self-assembling peptide D-RADA16 and L-RADA16 are both found to produce stable β-sheet secondary structure and nanofiber hydrogel scaffolds based on circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM) and rheology analysis etc. D-RADA16 hydrogel and L-RADA16 hydrogel can enhance obvious bone repair in femoral condyle defects of the Sprague-Dawley (SD) rat model compared to PBS treatment. Based on micro-computed tomography (CT), it was revealed that D-RADA16 hydrogel and L-RADA16 hydrogel were capable to obtain the extensive bone healing. Histological evaluation also found that these two hydrogels facilitate the presence of more mature bone tissue within the femoral condyle defects. Additionally, D-RADA16 hydrogel showed some potential in storing and releasing basic-fibroblast growth factor (bFGF) which was able to further promote bone regeneration based on micro-CT analysis. These results indicate that D-form peptide nanofiber hydrogel have some special capacity for bone repair. - Highlights: • Peptide D-RADA16 and L-RADA16 can form stable hydrogels. • D-RADA16 hydrogel can obtain the comparable and extensive promotion to bone healing compared to L-RADA16 hydrogel. • L-RADA16 hydrogel allows for slow release of bFGF.

Cadmium tolerance and antibiotic resistance in Escherichia coli isolated from waste stabilization ponds.

Science.gov (United States)

Patra, Sova; Das, T K; Avila, C; Cabello, V; Castillo, F; Sarkar, D; Lahiri, Susmita; Jana, B B

2012-04-01

The incidence pattern of cadmium tolerance and antibiotics resistance by Escherichia coli was examined periodically from the samples of water, sludge and intestine of fish raised in waste stabilization ponds in a sewage treatment plant. Samples of water and sludge were collected from all the selected ponds and were monitored for total counts of fecal coliform (FC), total coliform (TC) and the population of Escherichia coli, which was also obtained from the intestine of fishes. Total counts of both FC and TC as well as counts of E. coli were markedly reduced from the facultative pond to the last maturation pond. Tolerance limit to cadmium by E. coli tended to decline as the distance of the sewage effluent from the source increased; the effective lethal concentration of cadmium ranged from 0.1 mM in split chamber to 0.05 mM in first maturation pond. E. coli isolated from water, sludge and fish gut were sensitive to seven out of ten antibiotics tested. It appears that holistic functions mediated through the mutualistic growth of micro algae and heterotrophic bacteria in the waste stabilization ponds were responsible for the promotion of water quality and significant reduction of coliform along the sewage effluent gradient.

Plant Growth, Antibiotic Uptake, and Prevalence of Antibiotic Resistance in an Endophytic System of Pakchoi under Antibiotic Exposure

Directory of Open Access Journals (Sweden)

Hao Zhang

2017-11-01

Full Text Available Antibiotic contamination in agroecosystems may cause serious problems, such as the proliferation of various antibiotic resistant bacteria and the spreading of antibiotic resistance genes (ARGs in the environment or even to human beings. However, it is unclear whether environmental antibiotics, antibiotic resistant bacteria, and ARGs can directly enter into, or occur in, the endophytic systems of plants exposed to pollutants. In this study, a hydroponic experiment exposing pakchoi (Brassica chinensis L. to tetracycline, cephalexin, and sulfamethoxazole at 50% minimum inhibitory concentration (MIC levels and MIC levels, respectively, was conducted to explore plant growth, antibiotic uptake, and the development of antibiotic resistance in endophytic systems. The three antibiotics promoted pakchoi growth at 50% MIC values. Target antibiotics at concentrations ranging from 6.9 to 48.1 µg·kg−1 were detected in the treated vegetables. Additionally, the rates of antibiotic-resistant endophytic bacteria to total cultivable endophytic bacteria significantly increased as the antibiotics accumulated in the plants. The detection and quantification of ARGs indicated that four types, tetX, blaCTX-M, and sul1 and sul2, which correspond to tetracycline, cephalexin, and sulfamethoxazole resistance, respectively, were present in the pakchoi endophytic system and increased with the antibiotic concentrations. The results highlight a potential risk of the development and spread of antibiotic resistance in vegetable endophytic systems.

Plant Growth, Antibiotic Uptake, and Prevalence of Antibiotic Resistance in an Endophytic System of Pakchoi under Antibiotic Exposure.

Science.gov (United States)

Zhang, Hao; Li, Xunan; Yang, Qingxiang; Sun, Linlin; Yang, Xinxin; Zhou, Mingming; Deng, Rongzhen; Bi, Linqian

2017-11-03

Antibiotic contamination in agroecosystems may cause serious problems, such as the proliferation of various antibiotic resistant bacteria and the spreading of antibiotic resistance genes (ARGs) in the environment or even to human beings. However, it is unclear whether environmental antibiotics, antibiotic resistant bacteria, and ARGs can directly enter into, or occur in, the endophytic systems of plants exposed to pollutants. In this study, a hydroponic experiment exposing pakchoi ( Brassica chinensis L.) to tetracycline, cephalexin, and sulfamethoxazole at 50% minimum inhibitory concentration (MIC) levels and MIC levels, respectively, was conducted to explore plant growth, antibiotic uptake, and the development of antibiotic resistance in endophytic systems. The three antibiotics promoted pakchoi growth at 50% MIC values. Target antibiotics at concentrations ranging from 6.9 to 48.1 µg·kg -1 were detected in the treated vegetables. Additionally, the rates of antibiotic-resistant endophytic bacteria to total cultivable endophytic bacteria significantly increased as the antibiotics accumulated in the plants. The detection and quantification of ARGs indicated that four types, tet X, bla CTX-M , and sul 1 and sul 2, which correspond to tetracycline, cephalexin, and sulfamethoxazole resistance, respectively, were present in the pakchoi endophytic system and increased with the antibiotic concentrations. The results highlight a potential risk of the development and spread of antibiotic resistance in vegetable endophytic systems.

Fighting antibiotic resistance in the intensive care unit using antibiotics.

Science.gov (United States)

Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

2015-01-01

Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

Surface modified electrospun nanofibrous scaffolds for nerve tissue engineering

International Nuclear Information System (INIS)

Prabhakaran, Molamma P; Venugopal, J; Chan, Casey K; Ramakrishna, S

2008-01-01

The development of biodegradable polymeric scaffolds with surface properties that dominate interactions between the material and biological environment is of great interest in biomedical applications. In this regard, poly-ε-caprolactone (PCL) nanofibrous scaffolds were fabricated by an electrospinning process and surface modified by a simple plasma treatment process for enhancing the Schwann cell adhesion, proliferation and interactions with nanofibers necessary for nerve tissue formation. The hydrophilicity of surface modified PCL nanofibrous scaffolds (p-PCL) was evaluated by contact angle and x-ray photoelectron spectroscopy studies. Naturally derived polymers such as collagen are frequently used for the fabrication of biocomposite PCL/collagen scaffolds, though the feasibility of procuring large amounts of natural materials for clinical applications remains a concern, along with their cost and mechanical stability. The proliferation of Schwann cells on p-PCL nanofibrous scaffolds showed a 17% increase in cell proliferation compared to those on PCL/collagen nanofibrous scaffolds after 8 days of cell culture. Schwann cells were found to attach and proliferate on surface modified PCL nanofibrous scaffolds expressing bipolar elongations, retaining their normal morphology. The results of our study showed that plasma treated PCL nanofibrous scaffolds are a cost-effective material compared to PCL/collagen scaffolds, and can potentially serve as an ideal tissue engineered scaffold, especially for peripheral nerve regeneration.

Design of a bioresorbable polymeric scaffold for osteoblast culture

Science.gov (United States)

Ditaranto, Vincent M., Jr.

Bioresorbable polymeric scaffolds were designed for the purpose of growing rat osteosarcoma cells (ROS 17/2.8) using the compression molding method. The material used in the construction of the scaffolds was a mixture of polycaprolactone (PCL), Hydroxyapatite (HA), Glycerin (GL) and salt (NaCl) for porosity. The concentration of the several materials utilized, was determined by volume. Past research at the University of Massachusetts Lowell (UML) has successfully utilized the compression molding method for the construction of scaffolds, but was unable to accomplish the goal of long term cell survival and complete cellular proliferation throughout a three dimensional scaffold. This research investigated various concentrations of the materials and molding temperatures used for the manufacture of scaffolds in order to improve the scaffold design and address those issues. The design of the scaffold using the compression molding process is detailed in the Method and Materials section of this thesis. The porogen (salt) used for porosity was suspected as a possible source of contamination causing cell apoptosis in past studies. This research addressed the issues for cell survival and proliferation throughout a three dimensional scaffold. The leaching of the salt was one major design modification. This research successfully used ultrasonic leaching in addition to the passive method. Prior to cell culture, the scaffolds were irradiated to 2.75 Mrad, with cobalt-60 gamma radionuclide. The tissue culture consisted of two trials: (1) cell culture in scaffolds cleaned with passive leaching; (2) cell culture with scaffolds cleaned with ultrasonic leaching. Cell survival and proliferation was accomplished only with the addition of ultrasonic leaching of the scaffolds. Analysis of the scaffolds included Scanning Electron Microscopy (SEM), Nikon light microscopy and x-ray mapping of the calcium, sodium and chloride ion distribution. The cells were analyzed by Environmental Scanning

Multilayer porous UHMWPE scaffolds for bone defects replacement

International Nuclear Information System (INIS)

Maksimkin, A.V.; Senatov, F.S.; Anisimova, N.Yu.; Kiselevskiy, M.V.; Zalepugin, D.Yu.; Chernyshova, I.V.; Tilkunova, N.A.; Kaloshkin, S.D.

2017-01-01

Reconstruction of the structural integrity of the damaged bone tissue is an urgent problem. UHMWPE may be potentially used for the manufacture of porous implants simulating as closely as possible the porous cancellous bone tissue. But the extremely high molecular weight of the polymer does not allow using traditional methods of foaming. Porous and multilayer UHMWPE scaffolds with nonporous bulk layer and porous layer that mimics cancellous bone architecture were obtained by solid-state mixing, thermopressing and washing in subcritical water. Structural and mechanical properties of the samples were studied. Porous UHMWPE samples were also studied in vitro and in vivo. The pores of UHMWPE scaffold are open and interconnected. Volume porosity of the obtained samples was 79 ± 2%; the pore size range was 80–700 μm. Strong connection of the two layers in multilayer UHMWPE scaffolds was observed with decreased number of fusion defects. Functionality of implants based on multilayer UHMWPE scaffolds is provided by the fixation of scaffolds in the bone defect through ingrowths of the connective tissue into the pores, which ensures the maintenance of the animals' mobility - Highlights: • Porous UHMWPE scaffold mimics cancellous bone architecture, maintaining its flexibility. • Multilayer UHMWPE scaffold is able to simulate different types of bone tissue. • Fixation of scaffolds in the bone provides through ingrowths of the connective tissue into pores. • Multilayer UHMWPE scaffolds can be used for the formation of bone implants.

Multilayer porous UHMWPE scaffolds for bone defects replacement

Energy Technology Data Exchange (ETDEWEB)

Maksimkin, A.V. [National University of Science and Technology “MISIS”, Moscow (Russian Federation); Senatov, F.S., E-mail: senatov@misis.ru [National University of Science and Technology “MISIS”, Moscow (Russian Federation); Anisimova, N.Yu.; Kiselevskiy, M.V. [National University of Science and Technology “MISIS”, Moscow (Russian Federation); N.N. Blokhin Russian Cancer Research Center, Moscow (Russian Federation); Zalepugin, D.Yu.; Chernyshova, I.V.; Tilkunova, N.A. [State Plant of Medicinal Drugs, Moscow (Russian Federation); Kaloshkin, S.D. [National University of Science and Technology “MISIS”, Moscow (Russian Federation)

2017-04-01

Reconstruction of the structural integrity of the damaged bone tissue is an urgent problem. UHMWPE may be potentially used for the manufacture of porous implants simulating as closely as possible the porous cancellous bone tissue. But the extremely high molecular weight of the polymer does not allow using traditional methods of foaming. Porous and multilayer UHMWPE scaffolds with nonporous bulk layer and porous layer that mimics cancellous bone architecture were obtained by solid-state mixing, thermopressing and washing in subcritical water. Structural and mechanical properties of the samples were studied. Porous UHMWPE samples were also studied in vitro and in vivo. The pores of UHMWPE scaffold are open and interconnected. Volume porosity of the obtained samples was 79 ± 2%; the pore size range was 80–700 μm. Strong connection of the two layers in multilayer UHMWPE scaffolds was observed with decreased number of fusion defects. Functionality of implants based on multilayer UHMWPE scaffolds is provided by the fixation of scaffolds in the bone defect through ingrowths of the connective tissue into the pores, which ensures the maintenance of the animals' mobility - Highlights: • Porous UHMWPE scaffold mimics cancellous bone architecture, maintaining its flexibility. • Multilayer UHMWPE scaffold is able to simulate different types of bone tissue. • Fixation of scaffolds in the bone provides through ingrowths of the connective tissue into pores. • Multilayer UHMWPE scaffolds can be used for the formation of bone implants.

Highly charged cyanine fluorophores for trafficking scaffold degradation

International Nuclear Information System (INIS)

Owens, Eric A; Alyabyev, Sergey; Henary, Maged; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Park, GwangLi; Ashitate, Yoshitomo; Choi, Jungmun; Hong, Gloria H; Choi, Hak Soo; Lee, Sang Jin; Khang, Gilson

2013-01-01

Biodegradable scaffolds have been extensively used in the field of tissue engineering and regenerative medicine. However, noninvasive monitoring of in vivo scaffold degradation is still lacking. In order to develop a real-time trafficking technique, a series of meso-brominated near-infrared (NIR) fluorophores were synthesized and conjugated to biodegradable gelatin scaffolds. Since the pentamethine cyanine core is highly lipophilic, the side chain of each fluorophore was modified with either quaternary ammonium salts or sulfonate groups. The physicochemical properties such as lipophilicity and net charge of fluorophores played a key role in the fate of NIR-conjugated scaffolds in vivo after biodegradation. The positively charged fluorophore-conjugated scaffold fragments were found in salivary glands, lymph nodes, and most of the hepatobiliary excretion route. However, halogenated fluorophores intensively accumulated into lymph nodes and the liver. Interestingly, balanced-charged gelatin scaffolds were degraded into urine in a short period of time. These results demonstrate that the noninvasive optical imaging using NIR fluorophores can be useful for the translation of biodegradable scaffolds into the clinic. (paper)

Maturity and maturity models in lean construction

Directory of Open Access Journals (Sweden)

Claus Nesensohn

2014-03-01

Full Text Available In recent years there has been an increasing interest in maturity models in management-related disciplines; which reflects a growing recognition that becoming more mature and having a model to guide the route to maturity can help organisations in managing major transformational change. Lean Construction (LC is an increasingly important improvement approach that organisations seek to embed. This study explores how to apply the maturity models to LC. Hence the attitudes, opinions and experiences of key industry informants with high levels of knowledge of LC were investigated. To achieve this, a review of maturity models was conducted, and data for the analysis was collected through a sequential process involving three methods. First a group interview with seven key informants. Second a follow up discussion with the same individuals to investigate some of the issues raised in more depth. Third an online discussion held via LinkedIn in which members shared their views on some of the results. Overall, we found that there is a lack of common understanding as to what maturity means in LC, though there is general agreement that the concept of maturity is a suitable one to reflect the path of evolution for LC within organisations.

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

NARCIS (Netherlands)

Leibovici, Leonard; Paul, Mical; Garner, Paul; Sinclair, David J; Afshari, Arash; Pace, Nathan Leon; Cullum, Nicky; Williams, Hywel C; Smyth, Alan; Skoetz, Nicole; Del Mar, Chris; Schilder, Anne G M; Yahav, Dafna; Tovey, David

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This

Tubular inverse opal scaffolds for biomimetic vessels

Science.gov (United States)

Zhao, Ze; Wang, Jie; Lu, Jie; Yu, Yunru; Fu, Fanfan; Wang, Huan; Liu, Yuxiao; Zhao, Yuanjin; Gu, Zhongze

2016-07-01

There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially oriented elliptical pattern microstructures on their surfaces. It is demonstrated that these tailored tubular scaffolds can effectively make endothelial cells to form an integrated hollow tubular structure on their inner surface and induce smooth muscle cells to form a circumferential orientation on their outer surface. These features of our tubular scaffolds make them highly promising for the construction of biomimetic blood vessels.There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially

Teenaged Internet Tutors' Use of Scaffolding with Older Learners

Science.gov (United States)

Tambaum, Tiina

2017-01-01

This study analyses how teenaged instructors paired with older learners make use of scaffolding. Video data were categorised according to 15 types of direct scaffolding tactics, indirect scaffolding, and unused scaffolding opportunities. The results show that a teenager who is unprepared for the role of an instructor of Internet skills for older…

Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

International Nuclear Information System (INIS)

Zeng, Chao; Yang, Qiang; Zhu, Meifeng; Du, Lilong; Zhang, Jiamin; Ma, Xinlong; Xu, Baoshan; Wang, Lianyong

2014-01-01

Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus

Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zeng, Chao; Yang, Qiang [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhu, Meifeng [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Du, Lilong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhang, Jiamin [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ma, Xinlong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Xu, Baoshan, E-mail: xubaoshan99@126.com [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Wang, Lianyong, E-mail: wly@nankai.edu.cn [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China)

2014-04-01

Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus.

Scaffold hopping in drug discovery using inductive logic programming.

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Tsunoyama, Kazuhisa; Amini, Ata; Sternberg, Michael J E; Muggleton, Stephen H

2008-05-01

In chemoinformatics, searching for compounds which are structurally diverse and share a biological activity is called scaffold hopping. Scaffold hopping is important since it can be used to obtain alternative structures when the compound under development has unexpected side-effects. Pharmaceutical companies use scaffold hopping when they wish to circumvent prior patents for targets of interest. We propose a new method for scaffold hopping using inductive logic programming (ILP). ILP uses the observed spatial relationships between pharmacophore types in pretested active and inactive compounds and learns human-readable rules describing the diverse structures of active compounds. The ILP-based scaffold hopping method is compared to two previous algorithms (chemically advanced template search, CATS, and CATS3D) on 10 data sets with diverse scaffolds. The comparison shows that the ILP-based method is significantly better than random selection while the other two algorithms are not. In addition, the ILP-based method retrieves new active scaffolds which were not found by CATS and CATS3D. The results show that the ILP-based method is at least as good as the other methods in this study. ILP produces human-readable rules, which makes it possible to identify the three-dimensional features that lead to scaffold hopping. A minor variant of a rule learnt by ILP for scaffold hopping was subsequently found to cover an inhibitor identified by an independent study. This provides a successful result in a blind trial of the effectiveness of ILP to generate rules for scaffold hopping. We conclude that ILP provides a valuable new approach for scaffold hopping.

Development of a novel collagen-GAG nanofibrous scaffold via electrospinning

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Zhong Shaoping [Department of Chemical and Biomolecular Engineering, National University of Singapore, 10 Kent Ridge Crescent 119260 (Singapore); Teo, Wee Eong [Division of Bioengineering, National University of Singapore, 10 Kent Ridge Crescent 119260 (Singapore); Zhu Xiao [Singapore Eye Research Institute, Singapore National Eye Center, 11 Third Hospital Avenue, Singapore 168751 (Singapore); Beuerman, Roger [Singapore Eye Research Institute, Singapore National Eye Center, 11 Third Hospital Avenue, Singapore 168751 (Singapore); Ramakrishna, Seeram [Division of Bioengineering, National University of Singapore, 10 Kent Ridge Crescent 119260 (Singapore); Yung, Lin Yue Lanry [Department of Chemical and Biomolecular Engineering, National University of Singapore, 10 Kent Ridge Crescent 119260 (Singapore)]. E-mail: cheyly@nus.edu.sg

2007-03-15

Collagen and glycosaminoglycan (GAG) are native constituents of human tissues and are widely utilized to fabricate scaffolds serving as an analog of native extracellular matrix (ECM).The development of blended collagen and GAG scaffolds may potentially be used in many soft tissue engineering applications since the scaffolds mimic the structure and biological function of native ECM. In this study, we were able to obtain a novel nanofibrous collagen-GAG scaffold by electrospinning with collagen and chondroitin sulfate (CS), a widely used GAG. The electrospun collagen-GAG scaffold exhibited a uniform fiber structure in nano-scale diameter. By crosslinking with glutaraldehyde vapor, the collagen-GAG scaffolds could resist from collagenase degradation and enhance the biostability of the scaffolds. This led to the increased proliferation of rabbit conjunctiva fibroblast on the scaffolds. Incorporation of CS into collagen nanofibers without crosslinking did not increase the biostability but still promoted cell growth. In conclusion, the electrospun collagen-GAG scaffolds, with high surface-to-volume ratio, may potentially provide a better environment for tissue formation/biosynthesis compared with the traditional scaffolds.

Development of a novel collagen-GAG nanofibrous scaffold via electrospinning

International Nuclear Information System (INIS)

Zhong Shaoping; Teo, Wee Eong; Zhu Xiao; Beuerman, Roger; Ramakrishna, Seeram; Yung, Lin Yue Lanry

2007-01-01

Collagen and glycosaminoglycan (GAG) are native constituents of human tissues and are widely utilized to fabricate scaffolds serving as an analog of native extracellular matrix (ECM).The development of blended collagen and GAG scaffolds may potentially be used in many soft tissue engineering applications since the scaffolds mimic the structure and biological function of native ECM. In this study, we were able to obtain a novel nanofibrous collagen-GAG scaffold by electrospinning with collagen and chondroitin sulfate (CS), a widely used GAG. The electrospun collagen-GAG scaffold exhibited a uniform fiber structure in nano-scale diameter. By crosslinking with glutaraldehyde vapor, the collagen-GAG scaffolds could resist from collagenase degradation and enhance the biostability of the scaffolds. This led to the increased proliferation of rabbit conjunctiva fibroblast on the scaffolds. Incorporation of CS into collagen nanofibers without crosslinking did not increase the biostability but still promoted cell growth. In conclusion, the electrospun collagen-GAG scaffolds, with high surface-to-volume ratio, may potentially provide a better environment for tissue formation/biosynthesis compared with the traditional scaffolds

Strategies for osteochondral repair: Focus on scaffolds

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Seog-Jin Seo

2014-07-01

Full Text Available Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mechanical compression and restoration. Among the possible therapies, tissue engineering of osteochondral tissues has shown considerable promise where multiple approaches of utilizing cells, scaffolds, and signaling molecules have been pursued. This review focuses particularly on the importance of scaffold design and its role in the success of osteochondral tissue engineering. Biphasic and gradient composition with proper pore configurations are the basic design consideration for scaffolds. Surface modification is an essential technique to improve the scaffold function associated with cell regulation or delivery of signaling molecules. The use of functional scaffolds with a controllable delivery strategy of multiple signaling molecules is also considered a promising therapeutic approach. In this review, we updated the recent advances in scaffolding approaches for osteochondral tissue engineering.

A review: fabrication of porous polyurethane scaffolds.

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Janik, H; Marzec, M

2015-03-01

The aim of tissue engineering is the fabrication of three-dimensional scaffolds that can be used for the reconstruction and regeneration of damaged or deformed tissues and organs. A wide variety of techniques have been developed to create either fibrous or porous scaffolds from polymers, metals, composite materials and ceramics. However, the most promising materials are biodegradable polymers due to their comprehensive mechanical properties, ability to control the rate of degradation and similarities to natural tissue structures. Polyurethanes (PUs) are attractive candidates for scaffold fabrication, since they are biocompatible, and have excellent mechanical properties and mechanical flexibility. PU can be applied to various methods of porous scaffold fabrication, among which are solvent casting/particulate leaching, thermally induced phase separation, gas foaming, emulsion freeze-drying and melt moulding. Scaffold properties obtained by these techniques, including pore size, interconnectivity and total porosity, all depend on the thermal processing parameters, and the porogen agent and solvents used. In this review, various polyurethane systems for scaffolds are discussed, as well as methods of fabrication, including the latest developments, and their advantages and disadvantages. Copyright © 2014. Published by Elsevier B.V.

Scaffold library for tissue engineering: a geometric evaluation.

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Chantarapanich, Nattapon; Puttawibul, Puttisak; Sucharitpwatskul, Sedthawatt; Jeamwatthanachai, Pongnarin; Inglam, Samroeng; Sitthiseripratip, Kriskrai

2012-01-01

Tissue engineering scaffold is a biological substitute that aims to restore, to maintain, or to improve tissue functions. Currently available manufacturing technology, that is, additive manufacturing is essentially applied to fabricate the scaffold according to the predefined computer aided design (CAD) model. To develop scaffold CAD libraries, the polyhedrons could be used in the scaffold libraries development. In this present study, one hundred and nineteen polyhedron models were evaluated according to the established criteria. The proposed criteria included considerations on geometry, manufacturing feasibility, and mechanical strength of these polyhedrons. CAD and finite element (FE) method were employed as tools in evaluation. The result of evaluation revealed that the close-cellular scaffold included truncated octahedron, rhombicuboctahedron, and rhombitruncated cuboctahedron. In addition, the suitable polyhedrons for using as open-cellular scaffold libraries included hexahedron, truncated octahedron, truncated hexahedron, cuboctahedron, rhombicuboctahedron, and rhombitruncated cuboctahedron. However, not all pore size to beam thickness ratios (PO:BT) were good for making the open-cellular scaffold. The PO:BT ratio of each library, generating the enclosed pore inside the scaffold, was excluded to avoid the impossibility of material removal after the fabrication. The close-cellular libraries presented the constant porosity which is irrespective to the different pore sizes. The relationship between PO:BT ratio and porosity of open-cellular scaffold libraries was displayed in the form of Logistic Power function. The possibility of merging two different types of libraries to produce the composite structure was geometrically evaluated in terms of the intersection index and was mechanically evaluated by means of FE analysis to observe the stress level. The couples of polyhedrons presenting low intersection index and high stress level were excluded. Good couples for

Scaffold Library for Tissue Engineering: A Geometric Evaluation

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Nattapon Chantarapanich

2012-01-01

Full Text Available Tissue engineering scaffold is a biological substitute that aims to restore, to maintain, or to improve tissue functions. Currently available manufacturing technology, that is, additive manufacturing is essentially applied to fabricate the scaffold according to the predefined computer aided design (CAD model. To develop scaffold CAD libraries, the polyhedrons could be used in the scaffold libraries development. In this present study, one hundred and nineteen polyhedron models were evaluated according to the established criteria. The proposed criteria included considerations on geometry, manufacturing feasibility, and mechanical strength of these polyhedrons. CAD and finite element (FE method were employed as tools in evaluation. The result of evaluation revealed that the close-cellular scaffold included truncated octahedron, rhombicuboctahedron, and rhombitruncated cuboctahedron. In addition, the suitable polyhedrons for using as open-cellular scaffold libraries included hexahedron, truncated octahedron, truncated hexahedron, cuboctahedron, rhombicuboctahedron, and rhombitruncated cuboctahedron. However, not all pore size to beam thickness ratios (PO : BT were good for making the open-cellular scaffold. The PO : BT ratio of each library, generating the enclosed pore inside the scaffold, was excluded to avoid the impossibility of material removal after the fabrication. The close-cellular libraries presented the constant porosity which is irrespective to the different pore sizes. The relationship between PO : BT ratio and porosity of open-cellular scaffold libraries was displayed in the form of Logistic Power function. The possibility of merging two different types of libraries to produce the composite structure was geometrically evaluated in terms of the intersection index and was mechanically evaluated by means of FE analysis to observe the stress level. The couples of polyhedrons presenting low intersection index and high stress

Embroidered polymer-collagen hybrid scaffold variants for ligament tissue engineering.

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Hoyer, M; Drechsel, N; Meyer, M; Meier, C; Hinüber, C; Breier, A; Hahner, J; Heinrich, G; Rentsch, C; Garbe, L-A; Ertel, W; Schulze-Tanzil, G; Lohan, A

2014-10-01

Embroidery techniques and patterns used for scaffold production allow the adaption of biomechanical scaffold properties. The integration of collagen into embroidered polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) scaffolds could stimulate neo-tissue formation by anterior cruciate ligament (ACL) cells. Therefore, the aim of this study was to test embroidered P(LA-CL) and PDS scaffolds as hybrid scaffolds in combination with collagen hydrogel, sponge or foam for ligament tissue engineering. ACL cells were cultured on embroidered P(LA-CL) and PDS scaffolds without or with collagen supplementation. Cell adherence, vitality, morphology and ECM synthesis were analyzed. Irrespective of thread size, ACL cells seeded on P(LA-CL) scaffolds without collagen adhered and spread over the threads, whereas the cells formed clusters on PDS and larger areas remained cell-free. Using the collagen hydrogel, the scaffold colonization was limited by the gel instability. The collagen sponge layers integrated into the scaffolds were hardly penetrated by the cells. Collagen foams increased scaffold colonization in P(LA-CL) but did not facilitate direct cell-thread contacts in the PDS scaffolds. The results suggest embroidered P(LA-CL) scaffolds as a more promising basis for tissue engineering an ACL substitute than PDS due to superior cell attachment. Supplementation with a collagen foam presents a promising functionalization strategy. Copyright © 2014 Elsevier B.V. All rights reserved.

Scaffolds in regenerative endodontics: A review

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Gathani, Kinjal M.; Raghavendra, Srinidhi Surya

2016-01-01

Root canal therapy has enabled us to save numerous teeth over the years. The most desired outcome of endodontic treatment would be when diseased or nonvital pulp is replaced with healthy pulp tissue that would revitalize the teeth through regenerative endodontics. ‘A search was conducted using the Pubmed and MEDLINE databases for articles with the criteria ‘Platelet rich plasma’, ‘Platelet rich fibrin’, ‘Stem cells’, ‘Natural and artificial scaffolds’ from 1982–2015’. Tissues are organized as three-dimensional structures, and appropriate scaffolding is necessary to provide a spatially correct position of cell location and regulate differentiation, proliferation, or metabolism of the stem cells. Extracellular matrix molecules control the differentiation of stem cells, and an appropriate scaffold might selectively bind and localize cells, contain growth factors, and undergo biodegradation over time. Different scaffolds facilitate the regeneration of different tissues. To ensure a successful regenerative procedure, it is essential to have a thorough and precise knowledge about the suitable scaffold for the required tissue. This article gives a review on the different scaffolds providing an insight into the new developmental approaches on the horizon. PMID:27857762

Scaffolds in regenerative endodontics: A review

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Kinjal M Gathani

2016-01-01

Full Text Available Root canal therapy has enabled us to save numerous teeth over the years. The most desired outcome of endodontic treatment would be when diseased or nonvital pulp is replaced with healthy pulp tissue that would revitalize the teeth through regenerative endodontics. ′A search was conducted using the Pubmed and MEDLINE databases for articles with the criteria ′Platelet rich plasma′, ′Platelet rich fibrin′, ′Stem cells′, ′Natural and artificial scaffolds′ from 1982-2015′. Tissues are organized as three-dimensional structures, and appropriate scaffolding is necessary to provide a spatially correct position of cell location and regulate differentiation, proliferation, or metabolism of the stem cells. Extracellular matrix molecules control the differentiation of stem cells, and an appropriate scaffold might selectively bind and localize cells, contain growth factors, and undergo biodegradation over time. Different scaffolds facilitate the regeneration of different tissues. To ensure a successful regenerative procedure, it is essential to have a thorough and precise knowledge about the suitable scaffold for the required tissue. This article gives a review on the different scaffolds providing an insight into the new developmental approaches on the horizon.

Effects of scaffold surface morphology on cell adhesion and survival rate in vitreous cryopreservation of tenocyte-scaffold constructs

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Wang, Zhi [State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041 (China); Department of Bone and Joint Surgery, The affiliated hospital of Luzhou Medical College, Luzhou 646000 (China); Qing, Quan [Sichuan College of Traditional Chinese Medicine, Mianyang 621000 (China); Regenerative Medicine Research Center, West China Hospital of Sichuan University, Chengdu 610041 (China); Chen, Xi; Liu, Cheng-Jun; Luo, Jing-Cong [State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041 (China); Hu, Jin-Lian [Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong (China); Qin, Ting-Wu, E-mail: tingwuqin@hotmail.com [State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041 (China)

2016-12-01

Highlights: • The shapes of tenocytes varied when seeded on different surface of scaffolds. • Tenocytes were flat on smooth surface and spindle on micro-grooved surface. • Tenocytes were ellipse or spindle on porous surface. • Tenocytes got varying adhesion shape and elongation index on varying surfaces. • The tenocyte survival on porous surface was superior to the other two groups. - Abstract: The purpose of this study was to investigate the effects of scaffold surface morphology on cell adhesion and survival rate in vitreous cryopreservation of tenocyte-scaffold constructs. Tenocytes were obtained from tail tendons of rats. Polydimethylsiloxane (PDMS) was used to fabricate three types of scaffolds with varying surface morphological characteristics, i.e., smooth, micro-grooved, and porous surfaces, respectively. The tenocytes were seeded on the surfaces of the scaffolds to form tenocyte-scaffold constructs. The constructs were cryopreserved in a vitreous cryoprotectant (CPA) with a multi-step protocol. The cell adhesion to scaffolds was observed with electronic scanning microscopy (SEM). The elongation index of the living tenocytes and ratio of live/dead cell number were examined based on a live/dead dual fluorescent staining technique, and the survival rate of tenocytes was studied with flow cytometry (FC). The results showed the shapes of tenocytes varied between the different groups: flat or polygonal (on smooth surface), spindle (on micro-grooved surface), and spindle or ellipse (on porous surface). After thawing, the porous surface got the most living tenocytes and a higher survival rate, suggesting its potential application for vitreous cryopreservation of engineered tendon constructs.

Synergistic Effect of Carbon Nanotubes and Graphene on Diopside Scaffolds.

Science.gov (United States)

Liu, Tingting; Wu, Ping; Gao, Chengde; Feng, Pei; Xiao, Tao; Deng, Youwen; Shuai, Cijun; Peng, Shuping

2016-01-01

A synergetic effect between carbon nanotubes (CNTs) and graphene on diopside (Di) scaffolds was demonstrated. 3D network architecture in the matrix was formed through the 1D CNTs inlaid among the 2D graphene platelets (GNPs). The mechanical properties of the CNTs/GNPs/Di scaffolds were significantly improved compared with the CNTs/Di scaffolds and GNPs/Di scaffolds. In addition, the scaffolds exhibited excellent apatite-forming ability, a modest degradation rate, and stable mechanical properties in simulated body fluid (SBF). Moreover, cell culturing tests indicated that the scaffolds supported the cells attachment and proliferation. Taken together, the CNTs/GNPs/Di scaffolds offered great potential for bone tissue engineering.

Combating Antibiotic Resistance

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... Bacteria Phasing Out Certain Antibiotic Use in Farm Animals FDA: Cutting-Edge Technology Sheds Light on Antibiotic Resistance For More Information Antibiotics and Antibiotic Resistance Antimicrobial Resistance Information for Consumers and Health Professionals CDC: ...

Fabrication and Mechanical Characterization of Hydrogel Infused Network Silk Scaffolds

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Lakshminath Kundanati

2016-09-01

Full Text Available Development and characterization of porous scaffolds for tissue engineering and regenerative medicine is of great importance. In recent times, silk scaffolds were developed and successfully tested in tissue engineering and drug release applications. We developed a novel composite scaffold by mechanical infusion of silk hydrogel matrix into a highly porous network silk scaffold. The mechanical behaviour of these scaffolds was thoroughly examined for their possible use in load bearing applications. Firstly, unconfined compression experiments show that the denser composite scaffolds displayed significant enhancement in the elastic modulus as compared to either of the components. This effect was examined and further explained with the help of foam mechanics principles. Secondly, results from confined compression experiments that resemble loading of cartilage in confinement, showed nonlinear material responses for all scaffolds. Finally, the confined creep experiments were performed to calculate the hydraulic permeability of the scaffolds using soil mechanics principles. Our results show that composite scaffolds with some modifications can be a potential candidate for use of cartilage like applications. We hope such approaches help in developing novel scaffolds for tissue engineering by providing an understanding of the mechanics and can further be used to develop graded scaffolds by targeted infusion in specific regions.

Gelatin–PMVE/MA composite scaffold promotes expansion of embryonic stem cells

International Nuclear Information System (INIS)

Chhabra, Hemlata; Gupta, Priyanka; Verma, Paul J.; Jadhav, Sameer; Bellare, Jayesh R.

2014-01-01

We introduce a new composite scaffold of gelatin and polymethyl vinyl ether-alt-maleic anhydride (PMVE/MA) for expansion of embryonic stem cells (ESCs) in an in vitro environment. To optimize the scaffold, we prepared a gelatin scaffold (G) and three composite scaffolds namely GP-1, GP-2, and GP-3 with varying PMVE/MA concentrations (0.2–1%) and characterized them by scanning electron microscopy (SEM), swelling study, compression testing and FTIR. SEM micrographs revealed interconnected porous structure in all the scaffolds. The permissible hemolysis ratio and activation of platelets by scaffolds confirmed the hemocompatibility of scaffolds. Initial biocompatibility assessment of scaffolds was conducted using hepatocarcinoma (Hep G2) cells and adhesion, proliferation and infiltration of Hep G2 cells in depth of scaffolds were observed, proving the scaffold's biocompatibility. Further Oct4B2 mouse embryonic stem cells (mESCs), which harbor a green fluorescence protein transgene under regulatory control of the Oct4 promotor, were examined for expansion on scaffolds with MTT assay. The GP-2 scaffold demonstrated the best cell proliferation and was further explored for ESC adherence and infiltration in depth (SEM and confocal), and pluripotent state of mESCs was assessed with the expression of Oct4-GFP and stage-specific embryonic antigen-1 (SSEA-1). This study reports the first demonstration of biocompatibility of gelatin–PMVE/MA composite scaffold and presents this scaffold as a promising candidate for embryonic stem cell based tissue engineering. - Highlights: • Composite scaffolds of gelatin and PMVE/MA were prepared by freeze-drying method. • SEM micrographs showed porous structure in all scaffolds of varying pore dimension. • GP-2 composite exhibited better cellular response in comparison to other scaffolds. • mESCs proliferated and expressed Oct-4 and SSEA-1, when cultured on GP-2 scaffold

Gelatin–PMVE/MA composite scaffold promotes expansion of embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Chhabra, Hemlata [Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai (India); Gupta, Priyanka [Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai (India); IITB-Monash Research Academy, Mumbai (India); Department of Chemical Engineering, Monash University, Melbourne (Australia); Verma, Paul J. [Turretfield Research Centre, South Australian Research and Development Institute, Rosedale, South Australia (Australia); Jadhav, Sameer; Bellare, Jayesh R. [Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai (India)

2014-04-01

We introduce a new composite scaffold of gelatin and polymethyl vinyl ether-alt-maleic anhydride (PMVE/MA) for expansion of embryonic stem cells (ESCs) in an in vitro environment. To optimize the scaffold, we prepared a gelatin scaffold (G) and three composite scaffolds namely GP-1, GP-2, and GP-3 with varying PMVE/MA concentrations (0.2–1%) and characterized them by scanning electron microscopy (SEM), swelling study, compression testing and FTIR. SEM micrographs revealed interconnected porous structure in all the scaffolds. The permissible hemolysis ratio and activation of platelets by scaffolds confirmed the hemocompatibility of scaffolds. Initial biocompatibility assessment of scaffolds was conducted using hepatocarcinoma (Hep G2) cells and adhesion, proliferation and infiltration of Hep G2 cells in depth of scaffolds were observed, proving the scaffold's biocompatibility. Further Oct4B2 mouse embryonic stem cells (mESCs), which harbor a green fluorescence protein transgene under regulatory control of the Oct4 promotor, were examined for expansion on scaffolds with MTT assay. The GP-2 scaffold demonstrated the best cell proliferation and was further explored for ESC adherence and infiltration in depth (SEM and confocal), and pluripotent state of mESCs was assessed with the expression of Oct4-GFP and stage-specific embryonic antigen-1 (SSEA-1). This study reports the first demonstration of biocompatibility of gelatin–PMVE/MA composite scaffold and presents this scaffold as a promising candidate for embryonic stem cell based tissue engineering. - Highlights: • Composite scaffolds of gelatin and PMVE/MA were prepared by freeze-drying method. • SEM micrographs showed porous structure in all scaffolds of varying pore dimension. • GP-2 composite exhibited better cellular response in comparison to other scaffolds. • mESCs proliferated and expressed Oct-4 and SSEA-1, when cultured on GP-2 scaffold.

ASTM International Workshop on Standards & Measurements for Tissue Engineering Scaffolds

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Simon, Carl G.; Yaszemski, Michael J.; Ratcliffe, Anthony; Tomlins, Paul; Luginbuehl, Reto; Tesk, John A.

2016-01-01

The “Workshop on Standards & Measurements for Tissue Engineering Scaffolds” was held on May 21, 2013 in Indianapolis, IN and was sponsored by the ASTM International (ASTM). The purpose of the workshop was to identify the highest priority items for future standards work for scaffolds used in the development and manufacture of tissue engineered medical products (TEMPs). Eighteen speakers and 78 attendees met to assess current scaffold standards and to prioritize needs for future standards. A key finding was that the ASTM TEMPs subcommittees (F04.41-46) have many active “guide” documents for educational purposes, but that few standard “test methods” or “practices” have been published. Overwhelmingly, the most clearly identified need was standards for measuring the structure of scaffolds, followed by standards for biological characterization, including in vitro testing, animal models and cell-material interactions. The third most pressing need was to develop standards for assessing the mechanical properties of scaffolds. Additional needs included standards for assessing scaffold degradation, clinical outcomes with scaffolds, effects of sterilization on scaffolds, scaffold composition and drug release from scaffolds. Discussions also highlighted the need for additional scaffold reference materials and the need to use them for measurement traceability. Finally, dialogue emphasized the needs to promote the use of standards in scaffold fabrication, characterization, and commercialization and to assess the use and impact of standards in the TEMPs community. Many scaffold standard needs have been identified and focus should now turn to generating these standards to support the use of scaffolds in TEMPs. PMID:25220952

Scaffold translation: barriers between concept and clinic.

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Hollister, Scott J; Murphy, William L

2011-12-01

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges. © Mary Ann Liebert, Inc.

Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine

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Chien, Karen B.

Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood

A Review on Fabricating Tissue Scaffolds using Vat Photopolymerization.

Science.gov (United States)

Chartrain, Nicholas A; Williams, Christopher B; Whittington, Abby R

2018-05-09

Vat Photopolymerization (stereolithography, SLA), an Additive Manufacturing (AM) or 3D printing technology, holds particular promise for the fabrication of tissue scaffolds for use in regenerative medicine. Unlike traditional tissue scaffold fabrication techniques, SLA is capable of fabricating designed scaffolds through the selective photopolymerization of a photopolymer resin on the micron scale. SLA offers unprecedented control over scaffold porosity and permeability, as well as pore size, shape, and interconnectivity. Perhaps even more significantly, SLA can be used to fabricate vascular networks that may encourage angio and vasculogenesis. Fulfilling this potential requires the development of new photopolymers, the incorporation of biochemical factors into printed scaffolds, and an understanding of the effects scaffold geometry have on cell viability, proliferation, and differentiation. This review compares SLA to other scaffold fabrication techniques, highlights significant advances in the field, and offers a perspective on the field's challenges and future directions. Engineering de novo tissues continues to be challenging due, in part, to our inability to fabricate complex tissue scaffolds that can support cell proliferation and encourage the formation of developed tissue. The goal of this review is to first introduce the reader to traditional and Additive Manufacturing scaffold fabrication techniques. The bulk of this review will then focus on apprising the reader of current research and provide a perspective on the promising use of vat photopolymerization (stereolithography, SLA) for the fabrication of complex tissue scaffolds. Copyright © 2018. Published by Elsevier Ltd.

Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam.

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Chau Nguyen Dang Giang

Full Text Available The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX, 4 ng L-1 sulfadiazine (SDZ, 17 ng L-1 trimethoprim (TRIM, and 12 ng L-1 enrofloxacin (ENRO. These concentrations were lower than the predicted no effect concentrations (PNECs and minimum inhibitory concentrations (MICs, suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from <1 to 44 days, depending on the availability of sunlight and sediment. Among the studied antibiotics TRIM was the most persistent in water systems. TRIM was not susceptible to photodegradation, while the dissipation of ENRO and SDZ was influenced by photolysis. The recorded dissipation models gave good predictions of the occurrence and concentrations of TRIM, ENRO and SDZ in surface water. In summary, the currently measured concentrations of the investigated antibiotics are unlikely to cause immediate risks

Cell-matrix mechanical interaction in electrospun polymeric scaffolds for tissue engineering: Implications for scaffold design and performance.

Science.gov (United States)

Kennedy, Kelsey M; Bhaw-Luximon, Archana; Jhurry, Dhanjay

2017-03-01

Engineered scaffolds produced by electrospinning of biodegradable polymers offer a 3D, nanofibrous environment with controllable structural, chemical, and mechanical properties that mimic the extracellular matrix of native tissues and have shown promise for a number of tissue engineering applications. The microscale mechanical interactions between cells and electrospun matrices drive cell behaviors including migration and differentiation that are critical to promote tissue regeneration. Recent developments in understanding these mechanical interactions in electrospun environments are reviewed, with emphasis on how fiber geometry and polymer structure impact on the local mechanical properties of scaffolds, how altering the micromechanics cues cell behaviors, and how, in turn, cellular and extrinsic forces exerted on the matrix mechanically remodel an electrospun scaffold throughout tissue development. Techniques used to measure and visualize these mechanical interactions are described. We provide a critical outlook on technological gaps that must be overcome to advance the ability to design, assess, and manipulate the mechanical environment in electrospun scaffolds toward constructs that may be successfully applied in tissue engineering and regenerative medicine. Tissue engineering requires design of scaffolds that interact with cells to promote tissue development. Electrospinning is a promising technique for fabricating fibrous, biomimetic scaffolds. Effects of electrospun matrix microstructure and biochemical properties on cell behavior have been extensively reviewed previously; here, we consider cell-matrix interaction from a mechanical perspective. Micromechanical properties as a driver of cell behavior has been well established in planar substrates, but more recently, many studies have provided new insights into mechanical interaction in fibrillar, electrospun environments. This review provides readers with an overview of how electrospun scaffold mechanics and

Nano/macro porous bioactive glass scaffold

Science.gov (United States)

Wang, Shaojie

Bioactive glass (BG) and ceramics have been widely studied and developed as implants to replace hard tissues of the musculo-skeletal system, such as bones and teeth. Recently, instead of using bulk materials, which usually do not degrade rapidly enough and may remain in the human body for a long time, the idea of bioscaffold for tissue regeneration has generated much interest. An ideal bioscaffold is a porous material that would not only provide a three-dimensional structure for the regeneration of natural tissue, but also degrade gradually and, eventually be replaced by the natural tissue completely. Among various material choices the nano-macro dual porous BG appears as the most promising candidate for bioscaffold applications. Here macropores facilitate tissue growth while nanopores control degradation and enhance cell response. The surface area, which controls the degradation of scaffold can also be tuned by changing the nanopore size. However, fabrication of such 3D structure with desirable nano and macro pores has remained challenging. In this dissertation, sol-gel process combined with spinodal decomposition or polymer sponge replication method has been developed to fabricate the nano-macro porous BG scaffolds. Macropores up to 100microm are created by freezing polymer induced spinodal structure through sol-gel transition, while larger macropores (>200um) of predetermined size are obtained by the polymer sponge replication technique. The size of nanopores, which are inherent to the sol-gel method of glass fabrication, has been tailored using several approaches: Before gel point, small nanopores are generated using acid catalyst that leads to weakly-branched polymer-like network. On the other hand, larger nanopores are created with the base-catalyzed gel with highly-branched cluster-like structure. After the gel point, the nanostructure can be further modified by manipulating the sintering temperature and/or the ammonia concentration used in the solvent

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

Science.gov (United States)

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

2015-07-06

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

Exact approaches for scaffolding

OpenAIRE

Weller, Mathias; Chateau, Annie; Giroudeau, Rodolphe

2015-01-01

This paper presents new structural and algorithmic results around the scaffolding problem, which occurs prominently in next generation sequencing. The problem can be formalized as an optimization problem on a special graph, the "scaffold graph". We prove that the problem is polynomial if this graph is a tree by providing a dynamic programming algorithm for this case. This algorithm serves as a basis to deduce an exact algorithm for general graphs using a tree decomposition of the input. We ex...

Scaffolding Proteins: Not Such Innocent Bystanders

OpenAIRE

Smith, F. Donelson; Scott, John D.

2013-01-01

Sequential transfer of information from one enzyme to the next within the confines of a protein kinase scaffold enhances signal transduction. Though frequently considered to be inert organizational elements, two recent reports implicate kinase-scaffolding proteins as active participants in signal relay.

Glutathione-Disrupted Biofilms of Clinical Pseudomonas aeruginosa Strains Exhibit an Enhanced Antibiotic Effect and a Novel Biofilm Transcriptome

Science.gov (United States)

Das, Theerthankar; Ibugo, Amaye; Buckle, Edwina; Manefield, Mike; Manos, Jim

2016-01-01

Pseudomonas aeruginosa infections result in high morbidity and mortality rates for individuals with cystic fibrosis (CF), with premature death often occurring. These infections are complicated by the formation of biofilms in the sputum. Antibiotic therapy is stymied by antibiotic resistance of the biofilm matrix, making novel antibiofilm strategies highly desirable. Within P. aeruginosa biofilms, the redox factor pyocyanin enhances biofilm integrity by intercalating with extracellular DNA. The antioxidant glutathione (GSH) reacts with pyocyanin, disrupting intercalation. This study investigated GSH disruption by assaying the physiological effects of GSH and DNase I on biofilms of clinical CF isolates grown in CF artificial sputum medium (ASMDM+). Confocal scanning laser microscopy showed that 2 mM GSH, alone or combined with DNase I, significantly disrupted immature (24-h) biofilms of Australian epidemic strain (AES) isogens AES-1R and AES-1M. GSH alone greatly disrupted mature (72-h) AES-1R biofilms, resulting in significant differential expression of 587 genes, as indicated by RNA-sequencing (RNA-seq) analysis. Upregulated systems included cyclic diguanylate and pyoverdine biosynthesis, the type VI secretion system, nitrate metabolism, and translational machinery. Biofilm disruption with GSH revealed a cellular physiology distinct from those of mature and dispersed biofilms. RNA-seq results were validated by biochemical and quantitative PCR assays. Biofilms of a range of CF isolates disrupted with GSH and DNase I were significantly more susceptible to ciprofloxacin, and increased antibiotic effectiveness was achieved by increasing the GSH concentration. This study demonstrated that GSH, alone or with DNase I, represents an effective antibiofilm treatment when combined with appropriate antibiotics, pending in vivo studies. PMID:27161630

The expression of antibiotic resistance genes in antibiotic-producing bacteria.

Science.gov (United States)

Mak, Stefanie; Xu, Ye; Nodwell, Justin R

2014-08-01

Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. © 2014 John Wiley & Sons Ltd.

Mechanical anisotropy of titanium scaffolds

Directory of Open Access Journals (Sweden)

Rüegg Jasmine

2017-09-01

Full Text Available The clinical performance of an implant, e.g. for the treatment of large bone defects, depends on the implant material, anchorage, surface topography and chemistry, but also on the mechanical properties, like the stiffness. The latter can be adapted by the porosity. Whereas foams show isotropic mechanical properties, digitally modelled scaffolds can be designed with anisotropic behaviour. In this study, we designed and produced 3D scaffolds based on an orthogonal architecture and studied its angle-dependent stiffness. The aim was to produce scaffolds with different orientations of the microarchitecture by selective laser melting and compare the angle-specific mechanical behaviour with an in-silico simulation. The anisotropic characteristics of open-porous implants and technical limitations of the production process were studied.

HA/nylon 6,6 porous scaffolds fabricated by salt-leaching/solvent casting technique: effect of nano-sized filler content on scaffold properties

Directory of Open Access Journals (Sweden)

Mehrabanian M

2011-08-01

Full Text Available Mehran Mehrabanian1, Mojtaba Nasr-Esfahani21Member of Young Researchers Club, Najafabad Branch, Islamic Azad University, Isfahan, Iran; 2Department of Materials Science and Engineering, Najafabad Branch, Islamic Azad University, Isfahan, IranAbstract: Nanohydroxyapatite (n-HA/nylon 6,6 composite scaffolds were produced by means of the salt-leaching/solvent casting technique. NaCl with a distinct range size was used with the aim of optimizing the pore network. Composite powders with different n-HA contents (40%, 60% for scaffold fabrication were synthesized and tested. The composite scaffolds thus obtained were characterized for their microstructure, mechanical stability and strength, and bioactivity. The microstructure of the composite scaffolds possessed a well-developed interconnected porosity with approximate optimal pore size ranging from 200 to 500 µm, ideal for bone regeneration and vascularization. The mechanical properties of the composite scaffolds were evaluated by compressive strength and modulus tests, and the results confirmed their similarity to cortical bone. To characterize bioactivity, the composite scaffolds were immersed in simulated body fluid for different lengths of time and results monitored by scanning electron microscopy and energy dispersive X-ray microanalysis to determine formation of an apatite layer on the scaffold surface.Keywords: scaffold, nanohydroxyapatite, nylon 6,6, salt-leaching/solvent casting, bioactivity

Nerve regeneration using tubular scaffolds from biodegradable polyurethane.

Science.gov (United States)

Hausner, T; Schmidhammer, R; Zandieh, S; Hopf, R; Schultz, A; Gogolewski, S; Hertz, H; Redl, H

2007-01-01

In severe nerve lesion, nerve defects and in brachial plexus reconstruction, autologous nerve grafting is the golden standard. Although, nerve grafting technique is the best available approach a major disadvantages exists: there is a limited source of autologous nerve grafts. This study presents data on the use of tubular scaffolds with uniaxial pore orientation from experimental biodegradable polyurethanes coated with fibrin sealant to regenerate a 8 mm resected segment of rat sciatic nerve. Tubular scaffolds: prepared by extrusion of the polymer solution in DMF into water coagulation bath. The polymer used for the preparation of tubular scaffolds was a biodegradable polyurethane based on hexamethylene diisocyanate, poly(epsilon-caprolactone) and dianhydro-D-sorbitol. EXPERIMENTAL MODEL: Eighteen Sprague Dawley rats underwent mid-thigh sciatic nerve transection and were randomly assigned to two experimental groups with immediate repair: (1) tubular scaffold, (2) 180 degrees rotated sciatic nerve segment (control). Serial functional measurements (toe spread test, placing tests) were performed weekly from 3rd to 12th week after nerve repair. On week 12, electrophysiological assessment was performed. Sciatic nerve and scaffold/nerve grafts were harvested for histomorphometric analysis. Collagenic connective tissue, Schwann cells and axons were evaluated in the proximal nerve stump, the scaffold/nerve graft and the distal nerve stump. The implants have uniaxially-oriented pore structure with a pore size in the range of 2 micorm (the pore wall) and 75 x 700 microm (elongated pores in the implant lumen). The skin of the tubular implants was nonporous. Animals which underwent repair with tubular scaffolds of biodegradable polyurethanes coated with diluted fibrin sealant had no significant functional differences compared with the nerve graft group. Control group resulted in a trend-wise better electrophysiological recovery but did not show statistically significant

Porous 45S5 Bioglass®-based scaffolds using stereolithography: Effect of partial pre-sintering on structural and mechanical properties of scaffolds.

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Thavornyutikarn, Boonlom; Tesavibul, Passakorn; Sitthiseripratip, Kriskrai; Chatarapanich, Nattapon; Feltis, Bryce; Wright, Paul F A; Turney, Terence W

2017-06-01

Scaffolds made from 45S5 Bioglass® ceramic (BG) show clinical potential in bone regeneration due to their excellent bioactivity and ability to bond to natural bone tissue. However, porous BG scaffolds are limited by their mechanical integrity and by the substantial volume contractions occurring upon sintering. This study examines stereolithographic (SLA) methods to fabricate mechanically robust and porous Bioglass®-based ceramic scaffolds, with regular and interconnected pore networks and using various computer-aided design architectures. It was found that a diamond-like (DM) architecture gave scaffolds the most controllable results without any observable closed porosity in the fired scaffolds. When the pore dimensions of the DM scaffolds of the same porosity (~60vol%) were decreased from 700 to 400μm, the compressive strength values increased from 3.5 to 6.7MPa. In addition, smaller dimensional shrinkage could be obtained by employing partially pre-sintered bioglass, compared to standard 45S5 Bioglass®. Scaffolds derived from pre-sintered bioglass also showed marginally improved compressive strength. Copyright © 2017 Elsevier B.V. All rights reserved.

Scaffolds for peripheral nerve repair and reconstruction.

Science.gov (United States)

Yi, Sheng; Xu, Lai; Gu, Xiaosong

2018-06-02

Trauma-associated peripheral nerve defect is a widespread clinical problem. Autologous nerve grafting, the current gold standard technique for the treatment of peripheral nerve injury, has many internal disadvantages. Emerging studies showed that tissue engineered nerve graft is an effective substitute to autologous nerves. Tissue engineered nerve graft is generally composed of neural scaffolds and incorporating cells and molecules. A variety of biomaterials have been used to construct neural scaffolds, the main component of tissue engineered nerve graft. Synthetic polymers (e.g. silicone, polyglycolic acid, and poly(lactic-co-glycolic acid)) and natural materials (e.g. chitosan, silk fibroin, and extracellular matrix components) are commonly used along or together to build neural scaffolds. Many other materials, including the extracellular matrix, glass fabrics, ceramics, and metallic materials, have also been used to construct neural scaffolds. These biomaterials are fabricated to create specific structures and surface features. Seeding supporting cells and/or incorporating neurotrophic factors to neural scaffolds further improve restoration effects. Preliminary studies demonstrate that clinical applications of these neural scaffolds achieve satisfactory functional recovery. Therefore, tissue engineered nerve graft provides a good alternative to autologous nerve graft and represents a promising frontier in neural tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

Bony defect repair in rabbit using hybrid rapid prototyping polylactic co glycolic acid/β tricalciumphosphate collagen I/apatite scaffold and bone marrow mesenchymal stem cells

Directory of Open Access Journals (Sweden)

Long Pang

2013-01-01

Full Text Available Background: In bone tissue engineering, extracellular matrix exerts critical influence on cellular interaction with porous biomaterial and the apatite playing an important role in the bonding process of biomaterial to bone tissue. The aim of this study was to observe the therapeutic effects of hybrid rapid prototyping (RP scaffolds comprising polylactic-co-glycolic acid (PLGA, β-tricalciumphosphate (β-TCP, collagen I and apatite (PLGA/β-TCP-collagen I/apatite on segmental bone defects in conjunction with combination with bone marrow mesenchymal stem cells (BMSCs. Materials and Methods: BMSCs were seeded into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits. Radiograph, microcomputed tomography and histology were used to evaluate new bone formation. Results: Radiographic analysis done from 12 to 36 weeks postoperative period demonstrated that new bone formed at the radial defect site and continues to increase until the medullary cavity is recanalized and remodelling is complete. The bone defect remained unconnected in the original RP scaffolds (PLGA/β-TCP during the whole study. Histological observations conformed to the radiographic images. In hybrid RP scaffold group, woven bone united the radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks postoperation and finally matured into cortical bone with normal marrow cavity after another 12 weeks. No bone formation but connective tissue has been detected in RP scaffold at the same time. Conclusion: Collagen I/apatite sponge composite coating could improve new bone formation in vivo. The hybrid RP scaffold of PLGA/β-TCP skeleton with collagen I/apatite sponge composite coating is a promising candidate for bone tissue engineering.

The antibiotic resistome.

Science.gov (United States)

Wright, Gerard D

2010-08-01

Antibiotics are essential for the treatment of bacterial infections and are among our most important drugs. Resistance has emerged to all classes of antibiotics in clinical use. Antibiotic resistance has, proven inevitable and very often it emerges rapidly after the introduction of a drug into the clinic. There is, therefore, a great interest in understanding the origins, scope and evolution of antibiotic resistance. The review discusses the concept of the antibiotic resistome, which is the collection of all genes that directly or indirectly contribute to antibiotic resistance. The review seeks to assemble current knowledge of the resistome concept as a means of understanding the totality of resistance and not just resistance in pathogenic bacteria. The concept of the antibiotic resistome provides a framework for the study and understanding of how resistance emerges and evolves. Furthermore, the study of the resistome reveals strategies that can be applied in new antibiotic discoveries.

SCAFFOLDING IN CONNECTIVIST MOBILE LEARNING ENVIRONMENT

Directory of Open Access Journals (Sweden)

Ozlem OZAN

2013-04-01

Full Text Available Social networks and mobile technologies are transforming learning ecology. In this changing learning environment, we find a variety of new learner needs. The aim of this study is to investigate how to provide scaffolding to the learners in connectivist mobile learning environment: Ø to learn in a networked environment, Ø to manage their networked learning process, Ø to interact in a networked society, and Ø to use the tools belonging to the network society. The researcher described how Vygotsky's “scaffolding” concept, Berge’s “learner support” strategies, and Siemens’ “connectivism” approach can be used together to satisfy mobile learners’ needs. A connectivist mobile learning environment was designed for the research, and the research was executed as a mixed-method study. Data collection tools were Facebook wall entries, personal messages, chat records; Twitter, Diigo, blog entries; emails, mobile learning management system statistics, perceived learning survey and demographic information survey. Results showed that there were four major aspects of scaffolding in connectivist mobile learning environment as type of it, provider of it, and timing of it and strategies of it. Participants preferred mostly social scaffolding, and then preferred respectively, managerial, instructional and technical scaffolding. Social scaffolding was mostly provided by peers, and managerial scaffolding was mostly provided by instructor. Use of mobile devices increased the learner motivation and interest. Some participants stated that learning was more permanent by using mobile technologies. Social networks and mobile technologies made it easier to manage the learning process and expressed a positive impact on perceived learning.

Low elastic modulus titanium–nickel scaffolds for bone implants

International Nuclear Information System (INIS)

Li, Jing; Yang, Hailin; Wang, Huifeng; Ruan, Jianming

2014-01-01

The superelastic nature of repeating the human bones is crucial to the ideal artificial biomedical implants to ensure smooth load transfer and foster the ingrowth of new bone tissues. Three dimensional interconnected porous TiNi scaffolds, which have the tailorable porous structures with micro-hole, were fabricated by slurry immersing with polymer sponge and sintering method. The crystallinity and phase composition of scaffolds were studied by X-ray diffraction. The pore morphology, size and distribution in the scaffolds were characterized by scanning electron microscopy. The porosity ranged from 65 to 72%, pore size was 250–500 μm. Compressive strength and elastic modulus of the scaffolds were ∼ 73 MPa and ∼ 3GPa respectively. The above pore structural and mechanical properties are similar to those of cancellous bone. In the initial cell culture test, osteoblasts adhered well to the scaffold surface during a short time, and then grew smoothly into the interconnected pore channels. These results indicate that the porous TiNi scaffolds fabricated by this method could be bone substitute materials. - Highlights: • A novel approach for the fabrication of porous TiNi scaffolds • Macroporous structures are replicated from the polymer sponge template. • The pore characteristics and mechanical properties of TiNi scaffolds agree well with the requirement of trabecular bone. • Cytocompatibility of TiNi scaffolds is assessed, and it closely associated with pore property

Development of keratin–chitosan–gelatin composite scaffold for soft tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Kakkar, Prachi [Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020 (India); Verma, Sudhanshu; Manjubala, I. [Biomedical Engineering Division, School of Bio Sciences and Technology, VIT University, Vellore 632014 (India); Madhan, B., E-mail: bmadhan76@yahoo.co.in [Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020 (India)

2014-12-01

Keratin has gained much attention in the recent past as a biomaterial for wound healing owing to its biocompatibility, biodegradability, intrinsic biological activity and presence of cellular binding motifs. In this paper, a novel biomimetic scaffold containing keratin, chitosan and gelatin was prepared by freeze drying method. The prepared keratin composite scaffold had good structural integrity. Fourier Transform Infrared (FTIR) spectroscopy showed the retention of the native structure of individual biopolymers (keratin, chitosan, and gelatin) used in the scaffold. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) results revealed a high thermal denaturation temperature of the scaffold (200–250 °C). The keratin composite scaffold exhibited tensile strength (96 kPa), compression strength (8.5 kPa) and water uptake capacity (> 1700%) comparable to that of a collagen scaffold, which was used as control. The morphology of the keratin composite scaffold observed using a Scanning Electron Microscope (SEM) exhibited good porosity and interconnectivity of pores. MTT assay using NIH 3T3 fibroblast cells demonstrated that the cell viability of the keratin composite scaffold was good. These observations suggest that the keratin–chitosan–gelatin composite scaffold is a promising alternative biomaterial for tissue engineering applications. - Highlights: • Fabrication of novel Keratin-Chitosan-Gelatin composite scaffold • Keratin composite scaffold shows excellent water uptake capacity and porosity • Keratin composite scaffold shows good thermal and physical stability • Biocompatibility of the developed scaffold is comparable to collagen scaffolds • Developed scaffold is a promising material for soft tissue engineering applications.

3D Printing of Scaffolds for Tissue Regeneration Applications

Science.gov (United States)

Do, Anh-Vu; Khorsand, Behnoush; Geary, Sean M.; Salem, Aliasger K.

2015-01-01

The current need for organ and tissue replacement, repair and regeneration for patients is continually growing such that supply is not meeting the high demand primarily due to a paucity of donors as well as biocompatibility issues that lead to immune rejection of the transplant. In an effort to overcome these drawbacks, scientists working in the field of tissue engineering and regenerative medicine have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the ultimate goal of yielding functional tissues or organs. Initial attempts at developing scaffolds were problematic and subsequently inspired a growing interest in 3D printing as a mode for generating scaffolds. Utilizing three-dimensional printing (3DP) technologies, ECM-like scaffolds can be produced with a high degree of complexity and precision, where fine details can be included at a micron level. In this review, we discuss the criteria for printing viable and functional scaffolds, scaffolding materials, and 3DP technologies used to print scaffolds for tissue engineering. A hybrid approach, employing both natural and synthetic materials, as well as multiple printing processes may be the key to yielding an ECM-like scaffold with high mechanical strength, porosity, interconnectivity, biocompatibility, biodegradability, and high processability. Creating such biofunctional scaffolds could potentially help to meet the demand by patients for tissues and organs without having to wait or rely on donors for transplantation. PMID:26097108

A gelatin composite scaffold strengthened by drug-loaded halloysite nanotubes.

Science.gov (United States)

Ji, Lijun; Qiao, Wei; Zhang, Yuheng; Wu, Huayu; Miao, Shiyong; Cheng, Zhilin; Gong, Qianming; Liang, Ji; Zhu, Aiping

2017-09-01

Mechanical properties and anti-infection are two of the most concerned issues for artificial bone grafting materials. Bone regeneration porous scaffolds with sustained drug release were developed by freeze-drying the mixture of nanosized drug-loaded halloysite nanotubes (HNTs) and gelatin. The scaffolds showed porous structure and excellent biocompatibility. The mechanical properties of the obtained composite scaffolds were enhanced significantly by HNTs to >300%, comparing to those of gelatin scaffold, and match to those of natural cancellous bones. The ibuprofen-loaded HNTs incorporated in the scaffolds allowed extended drug release over 100h, comparing to 8h when directly mixed the drug into the gelatin scaffold. The biological properties of the composite scaffolds were investigated by culturing MG63 cells on them. The HNTs/gelatin scaffolds with excellent mechanical properties and sustained drug release could be a promising artificial bone grating material. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

Science.gov (United States)

Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

2013-01-01

Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water. PMID:27029309

Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

Directory of Open Access Journals (Sweden)

Roderick I. Mackie

2013-07-01

Full Text Available Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

KAUST Repository

Hong, Pei-Ying; Aljassim, Nada I.; Ansari, Mohd Ikram; Mackie, Roderick

2013-01-01

Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

KAUST Repository

Hong, Pei-Ying

2013-07-31

Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

DEFF Research Database (Denmark)

Leibovici, Leonard; Paul, Mical; Garner, Paul

2016-01-01

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies....... This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should...... controlled trials or systematic reviews....

Bioactive Nano-fibrous Scaffold for Vascularized Craniofacial Bone Regeneration

DEFF Research Database (Denmark)

Prabha, Rahul Damodaran; Kraft, David Christian Evar; Harkness, Linda

2018-01-01

the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA) - poly (ε) caprolactone (PCL) - Bioceramic (HAB), namely, PVA-PCL-HAB. The scaffold prepared by dual...... electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic poly (ε) caprolactone (PCL) by combination with a hydrophilic polyvinyl alcohol (PVA) and the bioceramic (HAB) can contribute to enhance osteo-conductivity. We characterized the physicochemical...... and biocompatibility properties of the new scaffold material. Our results indicate PVA-PCL-HAB scaffolds support attachment and growth of stromal stem cells; (human bone marrow skeletal (mesenchymal) stem cells (hMSC) and dental pulp stem cells (DPSC)). In addition, the scaffold supported in vitro osteogenic...

Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies.

Science.gov (United States)

Taylor, Patrick K; Yeung, Amy T Y; Hancock, Robert E W

2014-12-10

The growth of bacteria as structured aggregates termed biofilms leads to their protection from harsh environmental conditions such as physical and chemical stresses, shearing forces, and limited nutrient availability. Because of this highly adapted ability to survive adverse environmental conditions, bacterial biofilms are recalcitrant to antibiotic therapies and immune clearance. This is particularly problematic in hospital settings where biofilms are a frequent cause of chronic and device-related infections and constitute a significant burden on the health-care system. The major therapeutic strategy against infections is the use of antibiotics, which, due to adaptive resistance, are often insufficient to clear biofilm infections. Thus, novel biofilm-specific therapies are required. Specific features of biofilm development, such as surface adherence, extracellular matrix formation, quorum sensing, and highly regulated biofilm maturation and dispersal are currently being studied as targets to be exploited in the development of novel biofilm-specific treatments. Using Pseudomonas aeruginosa for illustrative purposes, this review highlights the antibiotic resistance mechanisms of biofilms, and discusses current research into novel biofilm-specific therapies. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling material-degradation-induced elastic property of tissue engineering scaffolds.

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Bawolin, N K; Li, M G; Chen, X B; Zhang, W J

2010-11-01

The mechanical properties of tissue engineering scaffolds play a critical role in the success of repairing damaged tissues/organs. Determining the mechanical properties has proven to be a challenging task as these properties are not constant but depend upon time as the scaffold degrades. In this study, the modeling of the time-dependent mechanical properties of a scaffold is performed based on the concept of finite element model updating. This modeling approach contains three steps: (1) development of a finite element model for the effective mechanical properties of the scaffold, (2) parametrizing the finite element model by selecting parameters associated with the scaffold microstructure and/or material properties, which vary with scaffold degradation, and (3) identifying selected parameters as functions of time based on measurements from the tests on the scaffold mechanical properties as they degrade. To validate the developed model, scaffolds were made from the biocompatible polymer polycaprolactone (PCL) mixed with hydroxylapatite (HA) nanoparticles and their mechanical properties were examined in terms of the Young modulus. Based on the bulk degradation exhibited by the PCL/HA scaffold, the molecular weight was selected for model updating. With the identified molecular weight, the finite element model developed was effective for predicting the time-dependent mechanical properties of PCL/HA scaffolds during degradation.

Antibiotic therapy in preterm premature rupture of the membranes.

Science.gov (United States)

Yudin, Mark H; van Schalkwyk, Julie; Eyk, Nancy Van

2009-09-01

To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. 1. Following PPROM at 32 weeks' gestation, administration of antibiotics to prolong pregnancy is recommended if fetal lung maturity can not be proven and/or delivery is not planned. (I-A) 4

Chitin Scaffolds in Tissue Engineering

Science.gov (United States)

Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V.; Furuike, Tetsuya; Tamura, Hiroshi

2011-01-01

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine. PMID:21673928

Patterns of Scaffolding in Computer-Mediated Collaborative Inquiry

Science.gov (United States)

Lakkala, Minna; Muukkonen, Hanni; Hakkarainen, Kai

2005-01-01

There is wide agreement on the importance of scaffolding for student learning. Yet, models of individual and face-to-face scaffolding are not necessarily applicable to educational settings in which a group of learners is pursuing a process of inquiry mediated by technology. The scaffolding needed for such a process may be examined from three…

The response of tenocytes to commercial scaffolds used for rotator cuff repair

Directory of Open Access Journals (Sweden)

RDJ Smith

2017-01-01

Full Text Available Surgical repairs of rotator cuff tears have high re-tear rates and many scaffolds have been developed to augment the repair. Understanding the interaction between patients’ cells and scaffolds is important for improving scaffold performance and tendon healing. In this in vitro study, we investigated the response of patient-derived tenocytes to eight different scaffolds. Tested scaffolds included X-Repair, Poly-Tape, LARS Ligament, BioFiber (synthetic scaffolds, BioFiber-CM (biosynthetic scaffold, GraftJacket, Permacol, and Conexa (biological scaffolds. Cell attachment, proliferation, gene expression, and morphology were assessed. After one day, more cells attached to synthetic scaffolds with dense, fine and aligned fibres (X-Repair and Poly-Tape. Despite low initial cell attachment, the human dermal scaffold (GraftJacket promoted the greatest proliferation of cells over 13 days. Expression of collagen types I and III were upregulated in cells grown on non-cross-linked porcine dermis (Conexa. Interestingly, the ratio of collagen I to collagen III mRNA was lower on all dermal scaffolds compared to synthetic and biosynthetic scaffolds. These findings demonstrate significant differences in the response of patient-derived tendon cells to scaffolds that are routinely used for rotator cuff surgery. Synthetic scaffolds promoted increased cell adhesion and a tendon-like cellular phenotype, while biological scaffolds promoted cell proliferation and expression of collagen genes. However, no single scaffold was superior. Our results may help understand the way that patients’ cells interact with scaffolds and guide the development of new scaffolds in the future.

Biomimetic composite coating on rapid prototyped scaffolds for bone tissue engineering.

Science.gov (United States)

Arafat, M Tarik; Lam, Christopher X F; Ekaputra, Andrew K; Wong, Siew Yee; Li, Xu; Gibson, Ian

2011-02-01

The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Neural Stem Cells (NSCs in 3D Collagen Scaffolds: developing pharmacologically monitored neuroimplants for Spinal Cord Injury (SCI

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Alexandra Kourgiantaki

2014-06-01

Full Text Available Spinal cord injury, a traumatic disease characterised by a massive degeneration of neural tissue, was recently targeted for neuroregenerative interventions. Our approach is the development of pharmacologically pulsed neuroimplants using 3D collagen scaffolds hosting NSCs. We aim to monitor the properties of NSCs ex vivo and in vivo, using synthetic small molecules with neuroprotective and neurogenic properties. Synthetic, highly lipophilic CNS bioavailable small molecules, synthesized by our group (microneurotrophins, bind to neurotrophins receptors (Gravanis et al, Science Signaling, 2012, Calogeropoulou et al., J Med Chem., 2009. BNN27 can specifically interact with TrkA and p75NTR receptors activating specific signalling pathways controlling neuronal cell survival and neurogenesis (Charalampopoulos et al, PNAS, 2004, Lazaridis et al., PLoS Biol., 2011. We are seeding embryonic and adult mouse NSC on collagen 3D scaffolds of different composition (collagen, chondroitin-6-sulphate and gelatin and construction (size of pores and stiffness, testing cell behaviour (survival, proliferation or differentiation in basal conditions or pulsed with neurotrophins and/or microneurotrophins. Using the knock in sox2-egfp mice strain and fluorescence activated cell sorting (FACS analysis, we obtain NSCs cultures with a sox2-positive population more than 90% pure. We evaluate specific markers of proliferation (ki67 and/or differentiation (GFAP for glial cells, Tuj1 for mature neurons and O4 for oligodendrocytes: we are currently testing the possible effect of BNN27 on proliferation of cortical NSCs in 2D cultures (increased numbers of ki67 positive cells up to 12%. The composition and the structure of 3D scaffolds seem to play a significant functional role: scaffolds with a combined composition such as 50% collagen/50% gelatin and 92% collagen/8% chondroitin-6-sulphate support NSC survival since they sustain sox2 expression and propagate neurosphere formation

Edible Scaffolds Based on Non-Mammalian Biopolymers for Myoblast Growth

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Javier Enrione

2017-12-01

Full Text Available In vitro meat has recently emerged as a new concept in food biotechnology. Methods to produce in vitro meat generally involve the growth of muscle cells that are cultured on scaffolds using bioreactors. Suitable scaffold design and manufacture are critical to downstream culture and meat production. Most current scaffolds are based on mammalian-derived biomaterials, the use of which is counter to the desire to obviate mammal slaughter in artificial meat production. Consequently, most of the knowledge is related to the design and control of scaffold properties based on these mammalian-sourced materials. To address this, four different scaffold materials were formulated using non-mammalian sources, namely, salmon gelatin, alginate, and additives including gelling agents and plasticizers. The scaffolds were produced using a freeze-drying process, and the physical, mechanical, and biological properties of the scaffolds were evaluated. The most promising scaffolds were produced from salmon gelatin, alginate, agarose, and glycerol, which exhibited relatively large pore sizes (~200 μm diameter and biocompatibility, permitting myoblast cell adhesion (~40% and growth (~24 h duplication time. The biodegradation profiles of the scaffolds were followed, and were observed to be less than 25% after 4 weeks. The scaffolds enabled suitable myogenic response, with high cell proliferation, viability, and adequate cell distribution throughout. This system composed of non-mammalian edible scaffold material and muscle-cells is promising for the production of in vitro meat.

Cloning and heterologous expression of the antibiotic peptide (ABP) genes from Rhizopus oligosporus NBRC 8631.

Science.gov (United States)

Yamada, Osamu; Sakamoto, Kazutoshi; Tominaga, Mihoko; Nakayama, Tasuku; Koseki, Takuya; Fujita, Akiko; Akita, Osamu

2005-03-01

We carried out protein sequencing of purified Antibiotic Peptide (ABP), and cloned two genes encoding this peptide as abp1 and abp2, from Rhizopus oligosporus NBRC 8631. Both genes contain an almost identical 231-bp segment, with only 3 nucleotide substitutions, encoding a 77 amino acid peptide. The abp gene product comprises a 28 amino acid signal sequence and a 49 amino acid mature peptide. Northern blot analysis showed that at least one of the abp genes is transcribed in R. oligosporus NBRC 8631. A truncated form of abp1 encoding only the mature peptide was fused with the alpha-factor signal peptide and engineered for expression in Pichia pastoris SMD1168H. Culture broth of the recombinant Pichia displayed ABP activity against Bacillus subtilis NBRC 3335 after induction of heterologous gene expression. This result indicates that mature ABP formed the active structure without the aid of other factors from R. oligosporus, and was secreted.

A comparison of scaffold-free and scaffold-based reconstructed human skin models as alternatives to animal use.

Science.gov (United States)

Kinikoglu, Beste

2017-12-01

Tissue engineered full-thickness human skin substitutes have various applications in the clinic and in the laboratory, such as in the treatment of burns or deep skin defects, and as reconstructed human skin models in the safety testing of drugs and cosmetics and in the fundamental study of skin biology and pathology. So far, different approaches have been proposed for the generation of reconstructed skin, each with its own advantages and disadvantages. Here, the classic tissue engineering approach, based on cell-seeded polymeric scaffolds, is compared with the less-studied cell self-assembly approach, where the cells are coaxed to synthesise their own extracellular matrix (ECM). The resulting full-thickness human skin substitutes were analysed by means of histological and immunohistochemical analyses. It was found that both the scaffold-free and the scaffold-based skin equivalents successfully mimicked the functionality and morphology of native skin, with complete epidermal differentiation (as determined by the expression of filaggrin), the presence of a continuous basement membrane expressing collagen VII, and new ECM deposition by dermal fibroblasts. On the other hand, the scaffold-free model had a thicker epidermis and a significantly higher number of Ki67-positive proliferative cells, indicating a higher capacity for self-renewal, as compared to the scaffold-based model. 2017 FRAME.

Engineered polycaprolactone–magnesium hybrid biodegradable porous scaffold for bone tissue engineering

Directory of Open Access Journals (Sweden)

Hoi Man Wong

2014-10-01

Full Text Available In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone (PCL and magnesium (Mg micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.

ASTM international workshop on standards and measurements for tissue engineering scaffolds.

Science.gov (United States)

Simon, Carl G; Yaszemski, Michael J; Ratcliffe, Anthony; Tomlins, Paul; Luginbuehl, Reto; Tesk, John A

2015-07-01

The "Workshop on Standards & Measurements for Tissue Engineering Scaffolds" was held on May 21, 2013 in Indianapolis, IN, and was sponsored by the ASTM International (ASTM). The purpose of the workshop was to identify the highest priority items for future standards work for scaffolds used in the development and manufacture of tissue engineered medical products (TEMPs). Eighteen speakers and 78 attendees met to assess current scaffold standards and to prioritize needs for future standards. A key finding was that the ASTM TEMPs subcommittees (F04.41-46) have many active "guide" documents for educational purposes, but few standard "test methods" or "practices." Overwhelmingly, the most clearly identified need was standards for measuring the structure of scaffolds, followed by standards for biological characterization, including in vitro testing, animal models and cell-material interactions. The third most pressing need was to develop standards for assessing the mechanical properties of scaffolds. Additional needs included standards for assessing scaffold degradation, clinical outcomes with scaffolds, effects of sterilization on scaffolds, scaffold composition, and drug release from scaffolds. Discussions highlighted the need for additional scaffold reference materials and the need to use them for measurement traceability. Workshop participants emphasized the need to promote the use of standards in scaffold fabrication, characterization, and commercialization. Finally, participants noted that standards would be more broadly accepted if their impact in the TEMPs community could be quantified. Many scaffold standard needs have been identified and focus is turning to generating these standards to support the use of scaffolds in TEMPs. © 2014 Wiley Periodicals, Inc.

A scaffold easy to decontaminate

International Nuclear Information System (INIS)

Mourek, D.

1992-01-01

The conventional scaffold used in the assembling work and in revisions of technological facilities at nuclear power plants has many drawbacks. The most serious of them are a high amount of radioactive waste arising from the decontamination (planing) of the floor timber and from the discarding of damaged irreparable parts, and a considerable corrosion of the carbon steel supporting structure after the decontamination. A detailed description is given of a novel scaffold assembly which can be decontaminated and which exhibits many assets, in particular a good mechanical resistance (also to bad weather), a lower weight, and the use of prepreg floor girders for the construction of service platforms or scaffold bridges which can readily be assembled from the pressed pieces in a modular way. (Z.S.). 4 figs., 4 refs

Incorporation of zinc oxide nanoparticles into chitosan-collagen 3D porous scaffolds: Effect on morphology, mechanical properties and cytocompatibility of 3D porous scaffolds.

Science.gov (United States)

Ullah, Saleem; Zainol, Ismail; Idrus, Ruszymah Hj

2017-11-01

The zinc oxide nanoparticles (particles size chitosan-collagen 3D porous scaffolds and investigated the effect of zinc oxide nanoparticles incorporation on microstructure, mechanical properties, biodegradation and cytocompatibility of 3D porous scaffolds. The 0.5%, 1.0%, 2.0% and 4.0% zinc oxide nanoparticles chitosan-collagen 3D porous scaffolds were fabricated via freeze-drying technique. The zinc oxide nanoparticles incorporation effects consisting in chitosan-collagen 3D porous scaffolds were investigated by mechanical and swelling tests, and effect on the morphology of scaffolds examined microscopically. The biodegradation and cytocompatibility tests were used to investigate the effects of zinc oxide nanoparticles incorporation on the ability of scaffolds to use for tissue engineering application. The mean pore size and swelling ratio of scaffolds were decreased upon incorporation of zinc oxide nanoparticles however, the porosity, tensile modulus and biodegradation rate were increased upon incorporation of zinc oxide nanoparticles. In vitro culture of human fibroblasts and keratinocytes showed that the zinc oxide nanoparticles facilitated cell adhesion, proliferation and infiltration of chitosan-collagen 3D porous scaffolds. It was found that the zinc oxide nanoparticles incorporation enhanced porosity, tensile modulus and cytocompatibility of chitosan-collagen 3D porous scaffolds. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel mechanically competent polysaccharide scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Kumbar, S G; Toti, U S; Deng, M; James, R; Laurencin, C T; Aravamudhan, A; Harmon, M; Ramos, D M

2011-01-01

The success of the scaffold-based bone regeneration approach critically depends on the biomaterial's mechanical and biological properties. Cellulose and its derivatives are inherently associated with exceptional strength and biocompatibility due to their β-glycosidic linkage and extensive hydrogen bonding. This polymer class has a long medical history as a dialysis membrane, wound care system and pharmaceutical excipient. Recently cellulose-based scaffolds have been developed and evaluated for a variety of tissue engineering applications. In general porous polysaccharide scaffolds in spite of many merits lack the necessary mechanical competence needed for load-bearing applications. The present study reports the fabrication and characterization of three-dimensional (3D) porous sintered microsphere scaffolds based on cellulose derivatives using a solvent/non-solvent sintering approach for load-bearing applications. These 3D scaffolds exhibited a compressive modulus and strength in the mid-range of human trabecular bone and underwent degradation resulting in a weight loss of 10–15% after 24 weeks. A typical stress–strain curve for these scaffolds showed an initial elastic region and a less-stiff post-yield region similar to that of native bone. Human osteoblasts cultured on these scaffolds showed progressive growth with time and maintained expression of osteoblast phenotype markers. Further, the elevated expression of alkaline phosphatase and mineralization at early time points as compared to heat-sintered poly(lactic acid–glycolic acid) control scaffolds with identical pore properties affirmed the advantages of polysaccharides and their potential for scaffold-based bone regeneration.

Magnetic responsive hydroxyapatite composite scaffolds construction for bone defect reparation.

Science.gov (United States)

Zeng, Xiao Bo; Hu, Hao; Xie, Li Qin; Lan, Fang; Jiang, Wen; Wu, Yao; Gu, Zhong Wei

2012-01-01

In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. A type of magnetic scaffold composed of magnetic nanoparticles (MNPs) and hydroxyapatite (HA) for bone repair has been developed by our research group. In this study, to investigate the influence of the MNP content (in the scaffolds) on the cell behaviors and the interactions between the magnetic scaffold and the exterior magnetic field, a series of MNP-HA magnetic scaffolds with different MNP contents (from 0.2% to 2%) were fabricated by immersing HA scaffold into MNP colloid. ROS 17/2.8 and MC3T3-E1 cells were cultured on the scaffolds in vitro, with and without an exterior magnetic field, respectively. The cell adhesion, proliferation and differentiation were evaluated via scanning electron microscopy; confocal laser scanning microscopy; and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase, and bone gla protein activity tests. The results demonstrated the positive influence of the magnetic scaffolds on cell adhesion, proliferation, and differentiation. Further, a higher amount of MNPs on the magnetic scaffolds led to more significant stimulation. The magnetic scaffold can respond to the exterior magnetic field and engender some synergistic effect to intensify the stimulating effect of a magnetic field to the proliferation and differentiation of cells.

Scaffolding proteins: not such innocent bystanders.

Science.gov (United States)

Smith, F Donelson; Scott, John D

2013-06-17

Sequential transfer of information from one enzyme to the next within the confines of a protein kinase scaffold enhances signal transduction. Though frequently considered to be inert organizational elements, two recent reports implicate kinase-scaffolding proteins as active participants in signal relay. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preparation, physicochemical properties and biocompatibility of PBLG/PLGA/bioglass composite scaffolds

Energy Technology Data Exchange (ETDEWEB)

Cui, Ning [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Wang, Jinlei [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Ji, Chuanlei [The Orthopaedic Department, XiJing Hospital Affiliated to the Fourth Military Medical University, Xi' an 710032 (China); Xu, Weijun; Wang, Hongjie [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China)

2017-02-01

In this study, novel poly(γ-benzyl L-glutamate)/poly(lactic-co-glycolic acid)/bioglass (PBLG/PLGA/BG) composite scaffolds with different weight ratios were fabricated using a negative NaCl-templating method. The morphology, compression modulus and degradation kinetics of the scaffolds were characterized. The results showed that the PBLG/PLGA/BG composite scaffolds with a weight ratio of 5:5:1, namely PBLG5PLGA5BG composite scaffolds, displayed a pore size range of 50–500 μm, high compressive modulus (566.6 ± 8.8 kPa), suitable glass transition temperature (46.8 ± 0.2 °C) and low degradation rate (> 8 weeks). The in vitro biocompatibility of the scaffolds was evaluated with MC3T3-E1 cells by live-dead staining, MTT and ALP activity assays. The obtained results indicated that the PBLG5PLGA5BG composite scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells than PBLG and PBLG/PLGA composite scaffolds. The in vivo biocompatibility of the scaffolds was evaluated in both SD rat subcutaneous model and rabbit tibia defect model. The results of H&E, Masson's trichrome and CD34 staining assays demonstrated that the PBLG5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels more effectively than PBLG/PLGA composite scaffolds. The results of digital radiography confirmed that the PBLG5PLGA5BG composite scaffolds significantly improved in vivo osteogenesis. Collectively, the PBLG5PLGA5BG composite scaffolds could be a promising candidate for tissue engineering applications. - Highlights: • Foamy PBLG/PLGA/bioglass composite scaffolds were fabricated by negative templating. • PBLG/PLGA/bioglass composite scaffolds displayed tunable physicochemical properties. • PBLG/PLGA/bioglass composite scaffolds had good biocompatibility in vitro and in vivo. • PBLG/PLGA/bioglass composite scaffolds could promote the healing of bone defects.

Role of scaffold mean pore size in meniscus regeneration.

Science.gov (United States)

Zhang, Zheng-Zheng; Jiang, Dong; Ding, Jian-Xun; Wang, Shao-Jie; Zhang, Lei; Zhang, Ji-Ying; Qi, Yan-Song; Chen, Xue-Si; Yu, Jia-Kuo

2016-10-01

Recently, meniscus tissue engineering offers a promising management for meniscus regeneration. Although rarely reported, the microarchitectures of scaffolds can deeply influence the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation in meniscus tissue engineering. Herein, a series of three-dimensional (3D) poly(ε-caprolactone) (PCL) scaffolds with three distinct mean pore sizes (i.e., 215, 320, and 515μm) were fabricated via fused deposition modeling. The scaffold with the mean pore size of 215μm significantly improved both the proliferation and extracellular matrix (ECM) production/deposition of mesenchymal stem cells compared to all other groups in vitro. Moreover, scaffolds with mean pore size of 215μm exhibited the greatest tensile and compressive moduli in all the acellular and cellular studies. In addition, the relatively better results of fibrocartilaginous tissue formation and chondroprotection were observed in the 215μm scaffold group after substituting the rabbit medial meniscectomy for 12weeks. Overall, the mean pore size of 3D-printed PCL scaffold could affect cell behavior, ECM production, biomechanics, and repair effect significantly. The PCL scaffold with mean pore size of 215μm presented superior results both in vitro and in vivo, which could be an alternative for meniscus tissue engineering. Meniscus tissue engineering provides a promising strategy for meniscus regeneration. In this regard, the microarchitectures (e.g., mean pore size) of scaffolds remarkably impact the behaviors of cells and subsequent tissue formation, which has been rarely reported. Herein, three three-dimensional poly(ε-caprolactone) scaffolds with different mean pore sizes (i.e., 215, 320, and 515μm) were fabricated via fused deposition modeling. The results suggested that the mean pore size significantly affected the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation. This study furthers

Microfibrous silver-coated polymeric scaffolds with tunable mechanical properties

KAUST Repository

Kalakonda, Parvathalu.; Aldhahri, Musab A.; Abdel-wahab, Mohamed Shaaban; Tamayol, Ali; Moghaddam, K. Mollazadeh; Ben Rached, Fathia; Pain, Arnab; Khademhosseini, Ali; Memic, Adnan; Chaieb, Saharoui

2017-01-01

Electrospun scaffolds of poly(glycerol sebacate)/poly(ε-caprolactone) (PGS/PCL) have been used for engineered tissues due to their desirable thermal and mechanical properties as well as their tunable degradability. In this paper, we fabricated micro-fibrous scaffolds from a composite of PGS/PCL using a standard electrospinning method and coated them with silver (Ag). The low temperature coating method prevented substrate melting and the Ag coating decreases the pore size and increases the diameter of fibers which resulted in enhanced thermal and mechanical properties. We further compared the mechanical properties of the composite fibrous scaffolds with different thicknesses of Ag coated scaffolds. The composite fibrous scaffold with a 275 nm Ag coating showed higher tensile modulus (E) and ultimate tensile strength (UTS) without any post-processing treatment. Lastly, potential controlled release of the Ag coating from the composite fibrous scaffolds could present interesting biomedical applications.

Microfibrous silver-coated polymeric scaffolds with tunable mechanical properties

KAUST Repository

Kalakonda, Parvathalu.

2017-07-07

Electrospun scaffolds of poly(glycerol sebacate)/poly(ε-caprolactone) (PGS/PCL) have been used for engineered tissues due to their desirable thermal and mechanical properties as well as their tunable degradability. In this paper, we fabricated micro-fibrous scaffolds from a composite of PGS/PCL using a standard electrospinning method and coated them with silver (Ag). The low temperature coating method prevented substrate melting and the Ag coating decreases the pore size and increases the diameter of fibers which resulted in enhanced thermal and mechanical properties. We further compared the mechanical properties of the composite fibrous scaffolds with different thicknesses of Ag coated scaffolds. The composite fibrous scaffold with a 275 nm Ag coating showed higher tensile modulus (E) and ultimate tensile strength (UTS) without any post-processing treatment. Lastly, potential controlled release of the Ag coating from the composite fibrous scaffolds could present interesting biomedical applications.

Microporous dermal-like electrospun scaffolds promote accelerated skin regeneration.

Science.gov (United States)

Bonvallet, Paul P; Culpepper, Bonnie K; Bain, Jennifer L; Schultz, Matthew J; Thomas, Steven J; Bellis, Susan L

2014-09-01

The goal of this study was to synthesize skin substitutes that blend native extracellular matrix (ECM) molecules with synthetic polymers which have favorable mechanical properties. To this end, scaffolds were electrospun from collagen I (col) and poly(ɛ-caprolactone) (PCL), and then pores were introduced mechanically to promote fibroblast infiltration, and subsequent filling of the pores with ECM. A 70:30 col/PCL ratio was determined to provide optimal support for dermal fibroblast growth, and a pore diameter, 160 μm, was identified that enabled fibroblasts to infiltrate and fill pores with native matrix molecules, including fibronectin and collagen I. Mechanical testing of 70:30 col/PCL scaffolds with 160 μm pores revealed a tensile strength of 1.4 MPa, and the scaffolds also exhibited a low rate of contraction (pores. Keratinocytes formed a stratified layer on the surface of fibroblast-remodeled scaffolds, and staining for cytokeratin 10 revealed terminally differentiated keratinocytes at the apical surface. When implanted, 70:30 col/PCL scaffolds degraded within 3-4 weeks, an optimal time frame for degradation in vivo. Finally, 70:30 col/PCL scaffolds with or without 160 μm pores were implanted into full-thickness critical-sized skin defects. Relative to nonporous scaffolds or sham wounds, scaffolds with 160 μm pores induced accelerated wound closure, and stimulated regeneration of healthy dermal tissue, evidenced by a more normal-appearing matrix architecture, blood vessel in-growth, and hair follicle development. Collectively, these results suggest that microporous electrospun scaffolds are effective substrates for skin regeneration.

Improving antibiotic use in daily hospital practice : The antibiotic checklist

NARCIS (Netherlands)

van Daalen, F.V.

2018-01-01

Better use of current antibiotic agents is necessary to help control antimicrobial resistance (AMR). Antibiotic stewardship programs (ASPs) are introduced to coordinate activities to measure and improve appropriate antibiotic use in daily hospital practice. This thesis shows how the introduction of

Investigation of cancer cell behavior on nanofibrous scaffolds

Energy Technology Data Exchange (ETDEWEB)

Szot, Christopher S.; Buchanan, Cara F. [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States); Gatenholm, Paul [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States); Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Goeteborg (Sweden); Rylander, Marissa Nichole [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States); Freeman, Joseph W., E-mail: jwfreeman@vt.edu [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States)

2011-01-01

Tissue engineering and the use of nanofibrous biomaterial scaffolds offer a unique perspective for studying cancer development in vitro. Current in vitro models of tumorigenesis are limited by the use of static, two-dimensional (2D) cell culture monolayers that lack the structural architecture necessary for cell-cell interaction and three-dimensional (3D) scaffolds that are too simplistic for studying basic pathological mechanisms. In this study, two nanofibrous biomaterials that mimic the structure of the extracellular matrix, bacterial cellulose and electrospun polycaprolactone (PCL)/collagen I, were investigated as potential 3D scaffolds for an in vitro cancer model. Multiple cancer cell lines were cultured on each scaffold material and monitored for cell viability, proliferation, adhesion, infiltration, and morphology. Both bacterial cellulose and electrospun PCL/collagen I, which have nano-scale structures on the order of 100-500 nm, have been used in many diverse tissue engineering applications. Cancer cell adhesion and growth were limited on bacterial cellulose, while all cellular processes were enhanced on the electrospun scaffolds. This initial analysis has demonstrated the potential of electrospun PCL/collagen I scaffolds toward the development of an improved 3D in vitro cancer model.

Intrinsic Osteoinductivity of Porous Titanium Scaffold for Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Maryam Tamaddon

2017-01-01

Full Text Available Large bone defects and nonunions are serious complications that are caused by extensive trauma or tumour. As traditional therapies fail to repair these critical-sized defects, tissue engineering scaffolds can be used to regenerate the damaged tissue. Highly porous titanium scaffolds, produced by selective laser sintering with mechanical properties in range of trabecular bone (compressive strength 35 MPa and modulus 73 MPa, can be used in these orthopaedic applications, if a stable mechanical fixation is provided. Hydroxyapatite coatings are generally considered essential and/or beneficial for bone formation; however, debonding of the coatings is one of the main concerns. We hypothesised that the titanium scaffolds have an intrinsic potential to induce bone formation without the need for a hydroxyapatite coating. In this paper, titanium scaffolds coated with hydroxyapatite using electrochemical method were fabricated and osteoinductivity of coated and noncoated scaffolds was compared in vitro. Alizarin Red quantification confirmed osteogenesis independent of coating. Bone formation and ingrowth into the titanium scaffolds were evaluated in sheep stifle joints. The examinations after 3 months revealed 70% bone ingrowth into the scaffold confirming its osteoinductive capacity. It is shown that the developed titanium scaffold has an intrinsic capacity for bone formation and is a suitable scaffold for bone tissue engineering.

Scaffold diversification enhances effectiveness of a superlibrary of hyperthermophilic proteins.

Science.gov (United States)

Hussain, Mahmud; Gera, Nimish; Hill, Andrew B; Rao, Balaji M

2013-01-18

The use of binding proteins from non-immunoglobulin scaffolds has become increasingly common in biotechnology and medicine. Typically, binders are isolated from a combinatorial library generated by mutating a single scaffold protein. In contrast, here we generated a "superlibrary" or "library-of-libraries" of 4 × 10(8) protein variants by mutagenesis of seven different hyperthermophilic proteins; six of the seven proteins have not been used as scaffolds prior to this study. Binding proteins for five different model targets were successfully isolated from this library. Binders obtained were derived from five out of the seven scaffolds. Strikingly, binders from this modestly sized superlibrary have affinities comparable or higher than those obtained from a library with 1000-fold higher sequence diversity but derived from a single stable scaffold. Thus scaffold diversification, i.e., randomization of multiple different scaffolds, is a powerful alternate strategy for combinatorial library construction.

Newly approved antibiotics and antibiotics reserved for resistant infections: Implications for emergency medicine.

Science.gov (United States)

Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa

2017-01-01

Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Human-like collagen/nano-hydroxyapatite scaffolds for the culture of chondrocytes

Energy Technology Data Exchange (ETDEWEB)

Jia, Liping; Duan, Zhiguang [Shaanxi Key Laboratory of Degradable Biomedical Materials, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Mi, Yu; Hui, Junfeng [Shaanxi Key Laboratory of Degradable Biomedical Materials, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Northwest University, 229 Taibai North Road, Xi' an, Shaanxi 710069 (China); Chang, Le [School of Chemical Engineering, Northwest University, Xi' an, Shaanxi 710069 (China)

2013-03-01

Three dimensional (3D) biodegradable porous scaffolds play a key role in cartilage tissue repair. Freeze-drying and cross-linking techniques were used to fabricate a 3D composite scaffold that combined the excellent biological characteristics of human-like collagen (HLC) and the outstanding mechanical properties of nano-hydroxyapatite (nHA). The scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and compression tests, using Relive Registered-Sign Artificial Bone (RAB) scaffolds as a control. HLC/nHA scaffolds displayed homogeneous interconnected macroporous structure and could withstand a compression stress of 2.67 {+-} 0.37 MPa, which was higher than that of the control group. Rabbit chondrocytes were seeded on the composite porous scaffolds and cultured for 21 days. Cell/scaffold constructs were examined using SEM, histological procedures, and biochemical assays for cell proliferation and the production of glycosaminoglycans (GAGs). The results indicated that HLC/nHA porous scaffolds were capable of encouraging cell adhesion, homogeneous distribution and abundant GAG synthesis, and maintaining natural chondrocyte morphology compared to RAB scaffolds. In conclusion, the presented data warrants the further exploration of HLC/nHA scaffolds as a potential biomimetic platform for chondrocytes in cartilage tissue engineering. - Highlights: Black-Right-Pointing-Pointer Human-like collagen was first used to prepare cartilage tissue engineering scaffold. Black-Right-Pointing-Pointer Genipin, a natural biological cross-linking agent, was introduced to treat scaffold. Black-Right-Pointing-Pointer We chose market product as a control.

Impact of antibiotics on necrotizing enterocolitis and antibiotic-associated diarrhea

Science.gov (United States)

Silverman, Michael A.; Konnikova, Liza; Gerber, Jeffrey S.

2017-01-01

Summary Antibiotics induce changes or dysbiosis of the intestinal microbiome. These antibiotic-induce changes may contribute to the pathogenesis of necrotizing enterocolitis (NEC) and antibiotic-associated diarrhea (AAD). Studies are beginning to unravel the contribution of specific groups of microbes to these diseases—most notably Gammaproteobacteria for NEC and bile acid- and carbohydrate-metabolizing microbes for AAD. Antibiotic-associated diarrhea occurs when antibiotic treatment induces diarrhea by altering the metabolic function of the patient’s intestinal microbiota leading to either an osmotic or infectious diarrhea, most notably Clostridium difficile infection (CDI). Antibiotic therapy impairs the host microbiota’s ability to resist colonization or expansion of pathogenic bacteria. In the case of CDI, there is growing evidence that microbiota-mediated bile acid metabolism is critical in the pathogenesis of this infection. Probiotics or other microbiota-targeted therapies may provide effective strategies to prevent and treat NEC and AAD. PMID:28164853

Porous poly (lactic-co-glycolide) microsphere sintered scaffolds for tissue repair applications

International Nuclear Information System (INIS)

Wang Yingjun; Shi Xuetao; Ren Li; Wang Chunming; Wang Dongan

2009-01-01

In this paper, a new route to preparing porous poly (lactic-co-glycolide) (PLGA) scaffolds for bone tissue repair applications was developed. Novel porous PLGA scaffolds were fabricated via microsphere sintered technique and gas forming technique. Ammonium bicarbonate was used to regulate porosity of these porous scaffolds. Porosity of the scaffolds, and cell attachment, viability and proliferation on the scaffolds were evaluated. The results indicated that PLGA porous scaffolds were with the porosity from around 30% to 95% by regulating ammonium bicarbonate content from 0 to 10%. We also found that PLGA porous microsphere scaffolds benefited cell attachment and viability. Taken together, the achieved porous scaffolds have controlled porosity and also support mesenchymal stem cell proliferation, which could serve as potential scaffolds for bone repair applications.

Reinforced nanohydroxyapatite/polyamide66 scaffolds by chitosan coating for bone tissue engineering.

Science.gov (United States)

Huang, Di; Zuo, Yi; Zou, Qin; Wang, Yanying; Gao, Shibo; Wang, Xiaoyan; Liu, Haohuai; Li, Yubao

2012-01-01

High porosity of scaffold is always accompanied by poor mechanical property; the aim of this study was to enhance the strength and modulus of the highly porous scaffold of nanohydroxyapatite/polyamide66 (n-HA/PA66) by coating chitosan (CS) and to investigate the effect of CS content on the scaffold physical properties and cytological properties. The results show that CS coating can reinforce the scaffold effectively. The compress modulus and strength of the CS coated n-HA/PA66 scaffolds are improved to 32.71 and 2.38 MPa, respectively, being about six times and five times of those of the uncoated scaffolds. Meanwhile, the scaffolds still exhibit a highly interconnected porous structure and the porosity is approximate about 78%, slightly lower than the value (84%) of uncoated scaffold. The cytological properties of scaffolds were also studied in vitro by cocultured with osteoblast-like MG63 cells. The cytological experiments demonstrate that the reinforced scaffolds display favorable cytocompatibility and have no significant difference with the uncoated n-HA/PA66 scaffolds. The CS reinforced n-HA/PA66 scaffolds can meet the basic mechanical requirement of bone tissue engineering scaffold, presenting a potential for biomedical application in bone reconstruction and repair. Copyright © 2011 Wiley Periodicals, Inc.

Maturity group classification and maturity locus genotyping of early-maturing soybean varieties from high-latitude cold regions.

Science.gov (United States)

Jia, Hongchang; Jiang, Bingjun; Wu, Cunxiang; Lu, Wencheng; Hou, Wensheng; Sun, Shi; Yan, Hongrui; Han, Tianfu

2014-01-01

With the migration of human beings, advances of agricultural sciences, evolution of planting patterns and global warming, soybeans have expanded to both tropical and high-latitude cold regions (HCRs). Unlike other regions, HCRs have much more significant and diverse photoperiods and temperature conditions over seasons or across latitudes, and HCR soybeans released there show rich diversity in maturity traits. However, HCR soybeans have not been as well classified into maturity groups (MGs) as other places. Therefore, it is necessary to identify MGs in HCRs and to genotype the maturity loci. Local varieties were collected from the northern part of Northeast China and the far-eastern region of Russia. Maturity group reference (MGR) soybeans of MGs MG000, MG00, and MG0 were used as references during field experiments. Both local varieties and MGR soybeans were planted for two years (2010-2011) in Heihe (N 50°15', E 127°27', H 168.5 m), China. The days to VE (emergence), R1 (beginning bloom) and R7 (beginning maturity) were recorded and statistically analyzed. Furthermore, some varieties were further genotyped at four molecularly-identified maturity loci E1, E2, E3 and E4. The HCR varieties were classified into MG0 or even more early-maturing. In Heihe, some varieties matured much earlier than MG000, which is the most early-maturing known MG, and clustered into a separate group. We designated the group as MG0000, following the convention of MGs. HCR soybeans had relatively stable days to beginning bloom from emergence. The HCR varieties diversified into genotypes of E1, E2, E3 and E4. These loci had different effects on maturity. HCRs diversify early-maturing MGs of soybean. MG0000, a new MG that matures much earlier than known MGs, was developed. HCR soybean breeding should focus more on shortening post-flowering reproductive growth. E1, E2, E3, and E4 function differentially.

Automated quality characterization of 3D printed bone scaffolds

Directory of Open Access Journals (Sweden)

Tzu-Liang Bill Tseng

2014-07-01

Full Text Available Optimization of design is an important step in obtaining tissue engineering scaffolds with appropriate shapes and inner microstructures. Different shapes and sizes of scaffolds are modeled using UGS NX 6.0 software with variable pore sizes. The quality issue we are concerned is the scaffold porosity, which is mainly caused by the fabrication inaccuracies. Bone scaffolds are usually characterized using a scanning electron microscope, but this study presents a new automated inspection and classification technique. Due to many numbers and size variations for the pores, the manual inspection of the fabricated scaffolds tends to be error-prone and costly. Manual inspection also raises the chance of contamination. Thus, non-contact, precise inspection is preferred. In this study, the critical dimensions are automatically measured by the vision camera. The measured data are analyzed to classify the quality characteristics. The automated inspection and classification techniques developed in this study are expected to improve the quality of the fabricated scaffolds and reduce the overall cost of manufacturing.

Biosynthetically Guided Structure-Activity Relationship Studies of Merochlorin A, an Antibiotic Marine Natural Product.

Science.gov (United States)

López-Pérez, Borja; Pepper, Henry P; Ma, Rong; Fawcett, Benjamin J; Pehere, Ashok D; Wei, Qi; Ji, Zengchun; Polyak, Steven W; Dai, Huanqin; Song, Fuhang; Abell, Andrew D; Zhang, Lixin; George, Jonathan H

2017-12-07

The onset of new multidrug-resistant strains of bacteria demands continuous development of antibacterial agents with new chemical scaffolds and mechanisms of action. We present the first structure-activity relationship (SAR) study of 16 derivatives of a structurally novel antibiotic merochlorin A that were designed using a biosynthetic blueprint. Our lead compounds are active against several Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are relatively nontoxic to human cell lines. Furthermore, derivative 12 c {(±)-(3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione} was found to inhibit the growth of Bacillus Calmette-Guérin (BCG)-infected cells at concentrations similar to rifampicin. These results outperform the natural product, underscoring the potential of merochlorin analogues as a new class of antibiotics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrospun Nanofiber Scaffolds with Gradations in Fiber Organization

Science.gov (United States)

Khandalavala, Karl; Jiang, Jiang; Shuler, Franklin D.; Xie, Jingwei

2015-01-01

The goal of this protocol is to report a simple method for generating nanofiber scaffolds with gradations in fiber organization and test their possible applications in controlling cell morphology/orientation. Nanofiber organization is controlled with a new fabrication apparatus that enables the gradual decrease of fiber organization in a scaffold. Changing the alignment of fibers is achieved through decreasing deposition time of random electrospun fibers on a uniaxially aligned fiber mat. By covering the collector with a moving barrier/mask, along the same axis as fiber deposition, the organizational structure is easily controlled. For tissue engineering purposes, adipose-derived stem cells can be seeded to these scaffolds. Stem cells undergo morphological changes as a result of their position on the varied organizational structure, and can potentially differentiate into different cell types depending on their locations. Additionally, the graded organization of fibers enhances the biomimicry of nanofiber scaffolds so they more closely resemble the natural orientations of collagen nanofibers at tendon-to-bone insertion site compared to traditional scaffolds. Through nanoencapsulation, the gradated fibers also afford the possibility to construct chemical gradients in fiber scaffolds, and thereby further strengthen their potential applications in fast screening of cell-materials interaction and interfacial tissue regeneration. This technique enables the production of continuous gradient scaffolds, but it also can potentially produce fibers in discrete steps by controlling the movement of the moving barrier/mask in a discrete fashion. PMID:25938562

High Antibiotic Consumption

DEFF Research Database (Denmark)

Malo, Sara; José Rabanaque, María; Feja, Cristina

2014-01-01

Heavy antibiotic users are those individuals with the highest exposure to antibiotics. They play an important role as contributors to the increasing risk of antimicrobial resistance. We applied different methods to identify and characterize the group of heavy antibiotic users in Spain as well...... as their exposure to antibiotics. Data on outpatient prescribing of antimicrobials (ATC J01) in 2010 were obtained from a prescription database covering Aragón (northeastern Spain). The antimicrobial consumption at the individual level was analysed both according to the volume of DDD and the number of packages...... purchased per year. Heavy antibiotic users were identified according to Lorenz curves and characterized by age, gender, and their antimicrobial prescription profile. Lorenz curves demonstrated substantial differences in the individual use of antimicrobials. Heavy antibiotic users (5% of individuals...

Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair.

Science.gov (United States)

Li, Xing; Zhao, Yannan; Cheng, Shixiang; Han, Sufang; Shu, Muya; Chen, Bing; Chen, Xuyi; Tang, Fengwu; Wang, Nuo; Tu, Yue; Wang, Bin; Xiao, Zhifeng; Zhang, Sai; Dai, Jianwu

2017-08-01

Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation. The neuronal regeneration eventually led to a significant locomotion recovery. Furthermore, LOCS implantation could also greatly decrease chondroitin sulfate proteoglycan (CSPG) deposition at the lesion site. These findings suggest that endogenous neurogenesis following acute complete SCI is achievable in species ranging from rodents to large animals via functional scaffold implantation. LOCS-based Cetuximab delivery system has a promising therapeutic effect on activating endogenous neurogenesis, reducing CSPGs deposition and improving motor function recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

Science.gov (United States)

Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

2017-05-01

Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Teaching language teachers scaffolding professional learning

CERN Document Server

Maggioli, Gabriel Diaz

2012-01-01

Teaching Language Teachers: Scaffolding Professional Learning provides an updated view of as well as a reader-friendly introduction to the field of Teaching Teachers, with special reference to language teaching. By taking a decidedly Sociocultural perspective, the book addresses the main role of the Teacher of Teachers (ToT) as that of scaffolding the professional learning of aspiring teachers.

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions.

Science.gov (United States)

Leibovici, Leonard; Paul, Mical; Garner, Paul; Sinclair, David J; Afshari, Arash; Pace, Nathan Leon; Cullum, Nicky; Williams, Hywel C; Smyth, Alan; Skoetz, Nicole; Del Mar, Chris; Schilder, Anne G M; Yahav, Dafna; Tovey, David

2016-09-01

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Modified gum arabic cross-linked gelatin scaffold for biomedical applications

International Nuclear Information System (INIS)

Sarika, P.R.; Cinthya, Kuriakose; Jayakrishnan, A.; Anilkumar, P.R.; James, Nirmala Rachel

2014-01-01

The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture. - Highlights: • Gum arabic cross-linked gelatin scaffold was developed for tissue engineering. • Cross-linking was achieved by Schiff's base reaction. • The scaffold is non-cytotoxic and non adherent to fibroblast and hepatocytes. • The scaffolds are potential candidates for spheroid cell culture

Modified gum arabic cross-linked gelatin scaffold for biomedical applications

Energy Technology Data Exchange (ETDEWEB)

Sarika, P.R. [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram, Kerala 695 547 (India); Cinthya, Kuriakose [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India); Jayakrishnan, A. [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600 036 (India); Anilkumar, P.R., E-mail: anilkumarpr@sctimst.ac.in [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Thiruvananthapuram, Kerala 695 012 (India); James, Nirmala Rachel, E-mail: nirmala@iist.ac.in [Department of Chemistry, Indian Institute of Space Science and Technology, Valiamala, Thiruvananthapuram, Kerala 695 547 (India)

2014-10-01

The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture. - Highlights: • Gum arabic cross-linked gelatin scaffold was developed for tissue engineering. • Cross-linking was achieved by Schiff's base reaction. • The scaffold is non-cytotoxic and non adherent to fibroblast and hepatocytes. • The scaffolds are potential candidates for spheroid cell culture.

Apple derived cellulose scaffolds for 3D mammalian cell culture.

Directory of Open Access Journals (Sweden)

Daniel J Modulevsky

Full Text Available There are numerous approaches for producing natural and synthetic 3D scaffolds that support the proliferation of mammalian cells. 3D scaffolds better represent the natural cellular microenvironment and have many potential applications in vitro and in vivo. Here, we demonstrate that 3D cellulose scaffolds produced by decellularizing apple hypanthium tissue can be employed for in vitro 3D culture of NIH3T3 fibroblasts, mouse C2C12 muscle myoblasts and human HeLa epithelial cells. We show that these cells can adhere, invade and proliferate in the cellulose scaffolds. In addition, biochemical functionalization or chemical cross-linking can be employed to control the surface biochemistry and/or mechanical properties of the scaffold. The cells retain high viability even after 12 continuous weeks of culture and can achieve cell densities comparable with other natural and synthetic scaffold materials. Apple derived cellulose scaffolds are easily produced, inexpensive and originate from a renewable source. Taken together, these results demonstrate that naturally derived cellulose scaffolds offer a complementary approach to existing techniques for the in vitro culture of mammalian cells in a 3D environment.

Improved cell activity on biodegradable photopolymer scaffolds using titanate nanotube coatings

Energy Technology Data Exchange (ETDEWEB)

Beke, S., E-mail: szabolcs.beke@iit.it [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Barenghi, R. [IEIIT, National Research Council (CNR), Via De Marini 6, 16149 Genova (Italy); Farkas, B.; Romano, I. [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Kőrösi, L. [Department of Biotechnology, Nanophage Therapy Center, Enviroinvest Corporation, Kertváros u. 2, H-7632 Pécs (Hungary); Scaglione, S. [IEIIT, National Research Council (CNR), Via De Marini 6, 16149 Genova (Italy); Brandi, F. [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, 56124-Pisa (Italy)

2014-11-01

The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308 nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we found that nanotubes coating affects cell viability and proliferation demonstrating that TNT coatings enhance cell growth on the scaffolds by further improving their surface topography. - Highlights: • Biodegradable scaffolds were produced by mask-assisted UV laser photocuring. • Titanate nanotube deposition was carried out without binding compounds or additives. • Titanate nanotube coatings enhanced cell viability and proliferation.

Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics

NARCIS (Netherlands)

Kimpen, JLL; van Houten, M.A.

In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies

Chitosan composite three dimensional macrospheric scaffolds for bone tissue engineering.

Science.gov (United States)

Vyas, Veena; Kaur, Tejinder; Thirugnanam, Arunachalam

2017-11-01

The present work deals with the fabrication of chitosan composite scaffolds with controllable and predictable internal architecture for bone tissue engineering. Chitosan (CS) based composites were developed by varying montmorillonite (MMT) and hydroxyapatite (HA) combinations to fabricate macrospheric three dimensional (3D) scaffolds by direct agglomeration of the sintered macrospheres. The fabricated CS, CS/MMT, CS/HA and CS/MMT/HA 3D scaffolds were characterized for their physicochemical, biological and mechanical properties. The XRD and ATR-FTIR studies confirmed the presence of the individual constituents and the molecular interaction between them, respectively. The reinforcement with HA and MMT showed reduced swelling and degradation rate. It was found that in comparison to pure CS, the CS/HA/MMT composites exhibited improved hemocompatibility and protein adsorption. The sintering of the macrospheres controlled the swelling ability of the scaffolds which played an important role in maintaining the mechanical strength of the 3D scaffolds. The CS/HA/MMT composite scaffold showed 14 folds increase in the compressive strength when compared to pure CS scaffolds. The fabricated scaffolds were also found to encourage the MG 63 cell proliferation. Hence, from the above studies it can be concluded that the CS/HA/MMT composite 3D macrospheric scaffolds have wider and more practical application in bone tissue regeneration applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomimetic mineral-organic composite scaffolds with controlled internal architecture.

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Manjubala, I; Woesz, Alexander; Pilz, Christine; Rumpler, Monika; Fratzl-Zelman, Nadja; Roschger, Paul; Stampfl, Juergen; Fratzl, Peter

2005-12-01

Bone and cartilage generation by three-dimensional scaffolds is one of the promising techniques in tissue engineering. One approach is to generate histologically and functionally normal tissue by delivering healthy cells in biocompatible scaffolds. These scaffolds provide the necessary support for cells to proliferate and maintain their differentiated function, and their architecture defines the ultimate shape. Rapid prototyping (RP) is a technology by which a complex 3-dimensional (3D) structure can be produced indirectly from computer aided design (CAD). The present study aims at developing a 3D organic-inorganic composite scaffold with defined internal architecture by a RP method utilizing a 3D printer to produce wax molds. The composite scaffolds consisting of chitosan and hydroxyapatite were prepared using soluble wax molds. The behaviour and response of MC3T3-E1 pre-osteoblast cells on the scaffolds was studied. During a culture period of two and three weeks, cell proliferation and in-growth were observed by phase contrast light microscopy, histological staining and electron microscopy. The Giemsa and Gömöri staining of the cells cultured on scaffolds showed that the cells proliferated not only on the surface, but also filled the micro pores of the scaffolds and produced extracellular matrix within the pores. The electron micrographs showed that the cells covering the surface of the struts were flattened and grew from the periphery into the middle region of the pores.

Manufacture of degradable polymeric scaffolds for bone regeneration.

Science.gov (United States)

Ge, Zigang; Jin, Zhaoxia; Cao, Tong

2008-06-01

Many innovative technology platforms for promoting bone regeneration have been developed. A common theme among these is the use of scaffolds to provide mechanical support and osteoconduction. Scaffolds can be either ceramic or polymer-based, or composites of both classes of material. Both ceramics and polymers have their own merits and drawbacks, and a better solution may be to synergize the advantageous properties of both materials within composite scaffolds. In this current review, after a brief introduction of the anatomy and physiology of bone, different strategies of fabricating polymeric scaffolds for bone regeneration, including traditional and solid free-form fabrication, are critically discussed and compared, while focusing on the advantages and disadvantages of individual techniques.

Manufacture of degradable polymeric scaffolds for bone regeneration

International Nuclear Information System (INIS)

Ge Zigang; Jin Zhaoxia; Cao Tong

2008-01-01

Many innovative technology platforms for promoting bone regeneration have been developed. A common theme among these is the use of scaffolds to provide mechanical support and osteoconduction. Scaffolds can be either ceramic or polymer-based, or composites of both classes of material. Both ceramics and polymers have their own merits and drawbacks, and a better solution may be to synergize the advantageous properties of both materials within composite scaffolds. In this current review, after a brief introduction of the anatomy and physiology of bone, different strategies of fabricating polymeric scaffolds for bone regeneration, including traditional and solid free-form fabrication, are critically discussed and compared, while focusing on the advantages and disadvantages of individual techniques. (topical review)

Hybrid Carbon-Based Scaffolds for Applications in Soft Tissue Reconstruction

Science.gov (United States)

Lafdi, Khalid; Joseph, Robert M.; Tsonis, Panagiotis A.

2012-01-01

Current biomedical scaffolds utilized in surgery to repair soft tissues commonly fail to meet the optimal combination of biomechanical and tissue regenerative properties. Carbon is a scaffold alternative that potentially optimizes the balance between mechanical strength, durability, and function as a cell and biologics delivery vehicle that is necessary to restore tissue function while promoting tissue repair. The goals of this study were to investigate the feasibility of fabricating hybrid fibrous carbon scaffolds modified with biopolymer, polycaprolactone and to analyze their mechanical properties and ability to support cell growth and proliferation. Environmental scanning electron microscopy, micro-computed tomography, and cell adhesion and cell proliferation studies were utilized to test scaffold suitability as a cell delivery vehicle. Mechanical properties were tested to examine load failure and elastic modulus. Results were compared to an acellular dermal matrix scaffold control (GraftJacket® [GJ] Matrix), selected for its common use in surgery for the repair of soft tissues. Results indicated that carbon scaffolds exhibited similar mechanical maximums and capacity to support fibroblast adhesion and proliferation in comparison with GJ. Fibroblast adhesion and proliferation was collinear with carbon fiber orientation in regions of sparsely distributed fibers and occurred in clusters in regions of higher fiber density and low porosity. Overall, fibroblast adhesion and proliferation was greatest in lower porosity carbon scaffolds with highly aligned fibers. Stepwise multivariate regression showed that the variability in maximum load of carbon scaffolds and controls were dependent on unique and separate sets of parameters. These finding suggested that there were significant differences in the functional implications of scaffold design and material properties between carbon and dermis derived scaffolds that affect scaffold utility as a tissue replacement

Characterization of Antibiotics and Antibiotic Resistance Genes on an Ecological Farm System

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Songhe Zhang

2015-01-01

Full Text Available There is a growing concern worldwide about the prevalence of antibiotics and antibiotic resistance genes (ARGs on the farm. In this study, we investigated the distribution of seven antibiotics and ten ARGs in fresh and dried pig feces, in biogas slurry, and in grape-planting soil from an ecological farm. Antibiotics including sulfamethazine, norfloxacin, ofloxacin, tetracycline, oxytetracycline, and chlortetracycline were detected in these samples (except for sulfamethoxazole in dried feces. In general, antibiotics levels in samples were in the sequence: biogas slurry > fresh feces > soil or dried feces. Results of ecological risk assessments revealed that among the seven antibiotics chlortetracycline showed the highest ecological risk. Among the ten ARGs, sulI and tetO were the most prevalent on this ecological farm. There were positive correlations between certain ARGs and the corresponding antibiotics on this ecological farm. Therefore, continuous monitoring of antibiotics and their corresponding ARGs should be conducted in the agroecosystem near the concentrated animal farming operation systems.

Biological effects of functionalizing copolymer scaffolds with nanodiamond particles.

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Xing, Zhe; Pedersen, Torbjorn O; Wu, Xujun; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Kloss, Frank R; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Mustafa, Kamal

2013-08-01

Significant evidence has indicated that poly(L-lactide)-co-(ɛ-caprolactone) [(poly(LLA-co-CL)] scaffolds could be one of the suitable candidates for bone tissue engineering. Oxygen-terminated nanodiamond particles (n-DP) were combined with poly(LLA-co-CL) and revealed to be positive for cell growth. In this study, we evaluated the influence of poly(LLA-co-CL) scaffolds modified by n-DP on attachment, proliferation, differentiation of bone marrow stromal cells (BMSCs) in vitro, and on bone formation using a sheep calvarial defect model. BMSCs were seeded on either poly(LLA-co-CL)- or n-DP-coated scaffolds and incubated for 1 h. Scanning electron microscopy (SEM) and fluorescence microscopy were used in addition to protein and DNA measurements to evaluate cellular attachment on the scaffolds. To determine the effect of n-DP on proliferation of BMSCs, cell/scaffold constructs were harvested after 3 days and evaluated by Bicinchoninic Acid (BCA) protein assay and SEM. In addition, the osteogenic differentiation of cells grown for 2 weeks on the various scaffolds and in a dynamic culture condition was evaluated by real-time RT-PCR. Unmodified and modified scaffolds were implanted into the calvaria of six-year-old sheep. The expression of collagen type I (COL I) and bone morphogenetic protein-2 (BMP-2) after 4 weeks as well as the formation of new bone after 12 and 24 weeks were analyzed by immunohistochemistry and histology. Scaffolds modified with n-DP supported increased cell attachment and the mRNA expression of osteopontin (OPN), bone sialoprotein (BSP), and BMP-2 were significantly increased after 2 weeks of culture. The BMSCs had spread well on the various scaffolds investigated after 3 days in the study with no significant difference in cell proliferation. Furthermore, the in vivo data revealed more positive staining of COL I and BMP-2 in relation to the n-DP-coated scaffolds after 4 weeks and presented more bone formation after 12 and 24 weeks. n

Access to antibiotics in New Delhi, India: implications for antibiotic policy.

Science.gov (United States)

Kotwani, Anita; Holloway, Kathleen

2013-01-01

The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology. DATA ON PROCUREMENT PRICE AND AVAILABILITY WAS COLLECTED FROM THREE PUBLIC HEALTHCARE PROVIDERS IN THE STATE: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n = 40) and chain pharmacies (n = 40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). PUBLIC SECTOR: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin + clavulanic acid, azithromycin, and cefuroxime aexitl. Inappropriate availability and pricing of newer

Laser printing of cells into 3D scaffolds

International Nuclear Information System (INIS)

Ovsianikov, A; Gruene, M; Koch, L; Maiorana, F; Chichkov, B; Pflaum, M; Wilhelmi, M; Haverich, A

2010-01-01

One of the most promising approaches in tissue engineering is the application of 3D scaffolds, which provide cell support and guidance in the initial tissue formation stage. The porosity of the scaffold and internal pore organization influence cell migration and play a major role in its biodegradation dynamics, nutrient diffusion and mechanical stability. In order to control cell migration and cellular interactions within the scaffold, novel technologies capable of producing 3D structures in accordance with predefined design are required. The two-photon polymerization (2PP) technique, used in this report for the fabrication of scaffolds, allows the realization of arbitrary 3D structures with submicron spatial resolution. Highly porous 3D scaffolds, produced by 2PP of acrylated poly(ethylene glycol), are seeded with cells by means of laser-induced forward transfer (LIFT). In this laser printing approach, a propulsive force, resulting from laser-induced shock wave, is used to propel individual cells or cell groups from a donor substrate towards the receiver substrate. We demonstrate that with this technique printing of multiple cell types into 3D scaffolds is possible. Combination of LIFT and 2PP provides a route for the realization of 3D multicellular tissue constructs and artificial ECM engineered on the microscale.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

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Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

2017-04-01

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have

Bionic Design, Materials and Performance of Bone Tissue Scaffolds

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Tong Wu

2017-10-01

Full Text Available Design, materials, and performance are important factors in the research of bone tissue scaffolds. This work briefly describes the bone scaffolds and their anatomic structure, as well as their biological and mechanical characteristics. Furthermore, we reviewed the characteristics of metal materials, inorganic materials, organic polymer materials, and composite materials. The importance of the bionic design in preoperative diagnosis models and customized bone scaffolds was also discussed, addressing both the bionic structure design (macro and micro structure and the bionic performance design (mechanical performance and biological performance. Materials and performance are the two main problems in the development of customized bone scaffolds. Bionic design is an effective way to solve these problems, which could improve the clinical application of bone scaffolds, by creating a balance between mechanical performance and biological performance.

Electrospun PVA-PCL-HAB scaffold for craniofacial bone regeneration

DEFF Research Database (Denmark)

Prabha, Rahul; Kraft, David Christian Evar; Melsen, Birte

2015-01-01

-caprolactone (PCL)- triphasic bioceramic(HAB) scaffold to biomimic native tissue and we tested its ability to support osteogenic differentiation of stromal stem cells ( MSC) and its suitability for regeneration of craniofa- cial defects. Physiochemical characterizations of the scaffold, including con- tact angle...... body fluid immersed scaffold samples. Culturing human adult dental pulp stem cells (DPSC) and human bone marrow derived MSC seeded on PVA-PCL-HAB scaffold showed enhanced cell proliferation and in vitro osteoblastic differentiation. Cell-containing scaffolds were implanted subcutaneously in immune...... deficient mice. Histologic ex- amination of retrieved implant sections stained with H&E, Col- lagenType I and Human Vimentin antibody demonstrated that the cells survived in vivo in the implants for at least 8 weeks with evidence of osteoblastic differentiation and angiogenesis within the implants. Our...

Prophylactic antibiotics versus post- operative antibiotics in herniorraphy

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Abedulla Khan Kayamkani

2015-07-01

Full Text Available Postoperative surgical site infections are a major source of illness.  Infection results in longer hospital stay and higher costs.  Uses of preoperative antibiotics have been standardized and are being used routinely in most clinical surgeries and include controversial areas like breast surgery and herniorraphy. Objective of the study is to find out the benefit of prophylactic use of antibiotics in the management of herniorraphy.This project was carried out in a multispeciality tertiary care teaching hospital from 1st-30th April in 2002. Group 1 patients were treated prophylactically half an hour before surgery with single dose of I.V. antibiotics (injection.  Ampicillin 1gm + injection.  Gentamicin 80mg. Group 2 patients were treated post surgery with capsule. Ampicillin 500mg 4 times a day for 7 days and injection. Gentamicin twice a day for first 4 days. In case of group 1 patients only one out of 20 patients (5% was infected.  Whereas in-group 2 patients 5 out of 20 patients (25% were infected. The cost of prophylactic antibiotic treatment was Rs. 25.56 per patient.  The postoperative antibiotic treatment cost was Rs. 220.4 per patient.  That means postoperative treatment is around 8.62 times costlier than prophylactic treatment.             From this study it is evident that prophylactic (preoperative treatment is better than postoperative treatment with antibiotics.

Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

Science.gov (United States)

Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

2018-01-01

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Magnetic responsive hydroxyapatite composite scaffolds construction for bone defect reparation

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Zeng XB

2012-07-01

Full Text Available Xiao Bo Zeng, Hao Hu, Li Qin Xie, Fang Lan, Wen Jiang, Yao Wu, Zhong Wei GuNational Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People's Republic of ChinaIntroduction: In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. A type of magnetic scaffold composed of magnetic nanoparticles (MNPs and hydroxyapatite (HA for bone repair has been developed by our research group.Aim and methods: In this study, to investigate the influence of the MNP content (in the scaffolds on the cell behaviors and the interactions between the magnetic scaffold and the exterior magnetic field, a series of MNP-HA magnetic scaffolds with different MNP contents (from 0.2% to 2% were fabricated by immersing HA scaffold into MNP colloid. ROS 17/2.8 and MC3T3-E1 cells were cultured on the scaffolds in vitro, with and without an exterior magnetic field, respectively. The cell adhesion, proliferation and differentiation were evaluated via scanning electron microscopy; confocal laser scanning microscopy; and 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, alkaline phosphatase, and bone gla protein activity tests.Results: The results demonstrated the positive influence of the magnetic scaffolds on cell adhesion, proliferation, and differentiation. Further, a higher amount of MNPs on the magnetic scaffolds led to more significant stimulation.Conclusion: The magnetic scaffold can respond to the exterior magnetic field and engender some synergistic effect to intensify the stimulating effect of a magnetic field to the proliferation and differentiation of cells.Keywords: magnetic therapy, magnetic nanoparticles, bone repair, magnetic responsive

Dynamic Scaffolding of Socially Regulated Learning in a Computer-Based Learning Environment

Science.gov (United States)

Molenaar, Inge; Roda, Claudia; van Boxtel, Carla; Sleegers, Peter

2012-01-01

The aim of this study is to test the effects of dynamically scaffolding social regulation of middle school students working in a computer-based learning environment. Dyads in the scaffolding condition (N=56) are supported with computer-generated scaffolds and students in the control condition (N=54) do not receive scaffolds. The scaffolds are…

Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

Science.gov (United States)

Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

2015-04-01

The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D

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Joachim Kohn

2012-03-01

Full Text Available Current methods for screening cell-material interactions typically utilize a two-dimensional (2D culture format where cells are cultured on flat surfaces. However, there is a need for combinatorial and high-throughput screening methods to systematically screen cell-biomaterial interactions in three-dimensional (3D tissue scaffolds for tissue engineering. Previously, we developed a two-syringe pump approach for making 3D scaffold gradients for use in combinatorial screening of salt-leached scaffolds. Herein, we demonstrate that the two-syringe pump approach can also be used to create scaffold gradients using a gas-foaming approach. Macroporous foams prepared by a gas-foaming technique are commonly used for fabrication of tissue engineering scaffolds due to their high interconnectivity and good mechanical properties. Gas-foamed scaffold gradient libraries were fabricated from two biodegradable tyrosine-derived polycarbonates: poly(desaminotyrosyl-tyrosine ethyl ester carbonate (pDTEc and poly(desaminotyrosyl-tyrosine octyl ester carbonate (pDTOc. The composition of the libraries was assessed with Fourier transform infrared spectroscopy (FTIR and showed that pDTEc/pDTOc gas-foamed scaffold gradients could be repeatably fabricated. Scanning electron microscopy showed that scaffold morphology was similar between the pDTEc-rich ends and the pDTOc-rich ends of the gradient. These results introduce a method for fabricating gas-foamed polymer scaffold gradients that can be used for combinatorial screening of cell-material interactions in 3D.

Heterogeneity of Scaffold Biomaterials in Tissue Engineering

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Lauren Edgar

2016-05-01

Full Text Available Tissue engineering (TE offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.

In vitro osteoclastogenesis on textile chitosan scaffold

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C Heinemann

2010-02-01

Full Text Available Textile chitosan fibre scaffolds were evaluated in terms of interaction with osteoclast-like cells, derived from human primary monocytes. Part of the scaffolds was further modified by coating with fibrillar collagen type I in order to make the surface biocompatible. Monocytes were cultured directly on the scaffolds in the presence of macrophage colony stimulating factor (M-CSF and receptor activator of nuclear factor kappaB ligand (RANKL for up to 18 days. Confocal laser scanning microscopy (CLSM as well as scanning electron microscopy (SEM revealed the formation of multinuclear osteoclast-like cells on both the raw chitosan fibres and the collagen-coated scaffolds. The modified surface supported the osteoclastogenesis. Differentiation towards the osteoclastic lineage was confirmed by the microscopic detection of cathepsin K, tartrate resistant acid phosphatase (TRAP, acidic compartments using 3-(2,4-dinitroanillino-3’-amino-N-methyldipropylamine (DAMP, immunological detection of TRAP isoform 5b, and analysis of gene expression of the osteoclastic markers TRAP, cathepsin K, vitronectin receptor, and calcitonin receptor using reverse transcription-polymerase chain reaction (RT-PCR. The feature of the collagen-coated but also of the raw chitosan fibre scaffolds to support attachment and differentiation of human monocytes facilitates cell-induced material resorption – one main requirement for successful bone tissue engineering.

Biocompatibility of hydroxyapatite scaffolds processed by lithography-based additive manufacturing.

Science.gov (United States)

Tesavibul, Passakorn; Chantaweroad, Surapol; Laohaprapanon, Apinya; Channasanon, Somruethai; Uppanan, Paweena; Tanodekaew, Siriporn; Chalermkarnnon, Prasert; Sitthiseripratip, Kriskrai

2015-01-01

The fabrication of hydroxyapatite scaffolds for bone tissue engineering applications by using lithography-based additive manufacturing techniques has been introduced due to the abilities to control porous structures with suitable resolutions. In this research, the use of hydroxyapatite cellular structures, which are processed by lithography-based additive manufacturing machine, as a bone tissue engineering scaffold was investigated. The utilization of digital light processing system for additive manufacturing machine in laboratory scale was performed in order to fabricate the hydroxyapatite scaffold, of which biocompatibilities were eventually evaluated by direct contact and cell-culturing tests. In addition, the density and compressive strength of the scaffolds were also characterized. The results show that the hydroxyapatite scaffold at 77% of porosity with 91% of theoretical density and 0.36 MPa of the compressive strength are able to be processed. In comparison with a conventionally sintered hydroxyapatite, the scaffold did not present any cytotoxic signs while the viability of cells at 95.1% was reported. After 14 days of cell-culturing tests, the scaffold was able to be attached by pre-osteoblasts (MC3T3-E1) leading to cell proliferation and differentiation. The hydroxyapatite scaffold for bone tissue engineering was able to be processed by the lithography-based additive manufacturing machine while the biocompatibilities were also confirmed.

One-Year Outcomes of Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold in an Ovine Model.

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Patel, Jay M; Merriam, Aaron R; Culp, Brian M; Gatt, Charles J; Dunn, Michael G

2016-04-01

Meniscus injuries and resulting meniscectomies lead to joint deterioration, causing pain, discomfort, and instability. Tissue-engineered devices to replace the meniscus have not shown consistent success with regard to function, mechanical integrity, or protection of cartilage. To evaluate a novel resorbable polymer fiber-reinforced meniscus reconstruction scaffold in an ovine model for 52 weeks and assess its integrity, tensile and compressive mechanics, cell phenotypes, matrix organization and content, and protection of the articular cartilage surfaces. Controlled laboratory study. Eight skeletally mature ewes were implanted with the fiber-reinforced scaffold after total meniscectomy, and 2 additional animals had untreated total meniscectomies. Animals were sacrificed at 52 weeks, and the explants and articular surfaces were analyzed macroscopically. Explants were characterized by ultimate tensile testing, confined compression creep testing, and biochemical, histological, and immunohistochemical analyses. Cartilage damage was characterized using the Mankin score on histologic slides from both the femur and tibia. One sheep was removed from the study because of a torn extensor tendon; the remaining 7 explants remained fully intact and incorporated into the bone tunnels. All explants exhibited functional tensile loads, tensile stiffnesses, and compressive moduli. Fibrocartilagenous repair with both types 1 and 2 collagen were observed, with areas of matrix organization and biochemical content similar to native tissue. Narrowing in the body region was observed in 5 of 7 explants. Mankin scores showed less cartilage damage in the explant group (femoral condyle: 3.43 ± 0.79, tibial plateau: 3.50 ± 1.63) than in the meniscectomy group (femoral condyle: 8.50 ± 3.54, tibial plateau: 6.75 ± 2.47) and were comparable with Mankin scores at the previously reported 16- and 32-week time points. A resorbable fiber-reinforced meniscus scaffold supports formation of functional

3D printing facilitated scaffold-free tissue unit fabrication

International Nuclear Information System (INIS)

Tan, Yu; Richards, Dylan J; Mei, Ying; Trusk, Thomas C; Visconti, Richard P; Yost, Michael J; Drake, Christopher J; Argraves, William Scott; Markwald, Roger R; Kindy, Mark S

2014-01-01

Tissue spheroids hold great potential in tissue engineering as building blocks to assemble into functional tissues. To date, agarose molds have been extensively used to facilitate fusion process of tissue spheroids. As a molding material, agarose typically requires low temperature plates for gelation and/or heated dispenser units. Here, we proposed and developed an alginate-based, direct 3D mold-printing technology: 3D printing microdroplets of alginate solution into biocompatible, bio-inert alginate hydrogel molds for the fabrication of scaffold-free tissue engineering constructs. Specifically, we developed a 3D printing technology to deposit microdroplets of alginate solution on calcium containing substrates in a layer-by-layer fashion to prepare ring-shaped 3D hydrogel molds. Tissue spheroids composed of 50% endothelial cells and 50% smooth muscle cells were robotically placed into the 3D printed alginate molds using a 3D printer, and were found to rapidly fuse into toroid-shaped tissue units. Histological and immunofluorescence analysis indicated that the cells secreted collagen type I playing a critical role in promoting cell–cell adhesion, tissue formation and maturation. (paper)

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

Energy Technology Data Exchange (ETDEWEB)

Shafiee, Abbas [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD (Australia); Seyedjafari, Ehsan [Department of Biotechnology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Sadat Taherzadeh, Elham [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Dinarvand, Peyman [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); The Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO (United States); Soleimani, Masoud [Hematology Department, Faculty of Medical Science, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: jafar_ai@tums.ac.ir [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2014-07-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

International Nuclear Information System (INIS)

Shafiee, Abbas; Seyedjafari, Ehsan; Sadat Taherzadeh, Elham; Dinarvand, Peyman; Soleimani, Masoud; Ai, Jafar

2014-01-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers

In vitro evaluation of crosslinked electrospun fish gelatin scaffolds

International Nuclear Information System (INIS)

Gomes, S.R.; Rodrigues, G.; Martins, G.G.; Henriques, C.M.R.; Silva, J.C.

2013-01-01

Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. - Highlights: ► Electrospinning of fish gelatin dissolved in both water or concentrated acetic acid ► Glutaraldehyde, genipin and dehydrothermal treatment effectively crosslink the fish gelatin fibers ► Fibroblasts effectively adhere to and propagate on all scaffolds ► Cell population is highest for glutaraldehyde crosslinked scaffolds ► Cells exhibit more filopodia and stress fibers on glutaraldehyde crosslinked scaffolds

In vitro evaluation of crosslinked electrospun fish gelatin scaffolds

Energy Technology Data Exchange (ETDEWEB)

Gomes, S.R. [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Rodrigues, G.; Martins, G.G. [Centro de Biologia Ambiental / Departamento de Biologia Animal, Faculdade de Ciências da Universidade de Lisboa, FCUL, 1749-016 Campo Grande, Lisboa (Portugal); Henriques, C.M.R. [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Silva, J.C., E-mail: jcs@fct.unl.pt [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

2013-04-01

Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. - Highlights: ► Electrospinning of fish gelatin dissolved in both water or concentrated acetic acid ► Glutaraldehyde, genipin and dehydrothermal treatment effectively crosslink the fish gelatin fibers ► Fibroblasts effectively adhere to and propagate on all scaffolds ► Cell population is highest for glutaraldehyde crosslinked scaffolds ► Cells exhibit more filopodia and stress fibers on glutaraldehyde crosslinked scaffolds.

A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies.

Science.gov (United States)

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Hansen, Ole Møller; Kristiansen, Asger Albæk; Le, Dang Quang Svend; Nielsen, Agnete Desirée; Nygaard, Jens Vinge; Bünger, Cody Erik; Lind, Martin

2012-06-01

To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide) scaffold. By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water-dioxane-PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT-PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O'Driscoll score. In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells. The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide scaffold with cells.

Accounting for structural compliance in nanoindentation measurements of bioceramic bone scaffolds

Science.gov (United States)

Juan Vivanco; Joseph E. Jakes; Josh Slane; Heidi-Lynn Ploeg

2014-01-01

Structural properties have been shown to be critical in the osteoconductive capacity and strength of bioactive ceramic bone scaffolds. Given the cellular foam-like structure of bone scaffolds, nanoindentation has been used as a technique to assess the mechanical properties of individual components of the scaffolds. Nevertheless, nanoindents placed on scaffolds may...

Mechanical and cytotoxicity evaluation of nanostructured hydroxyapatite-bredigite scaffolds for bone regeneration

Energy Technology Data Exchange (ETDEWEB)

Eilbagi, Marjan; Emadi, Rahmatollah; Raeissi, Keyvan [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Kharaziha, Mahshid, E-mail: ma.kharaziha@gmail.com [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Valiani, Ali [Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73441 (Iran, Islamic Republic of)

2016-11-01

Despite the attractive characteristics of three-dimensional pure hydroxyapatite (HA) scaffolds, due to their weak mechanical properties, researches have focused on the development of composite scaffolds via introducing suitable secondary components. The aim of this study was to develop, for the first time, three-dimensional HA-bredigite (Ca{sub 7}MgSi{sub 4}O{sub 16}) scaffolds containing various amounts of bredigite nanopowder (0, 5, 10 and 15 wt.%) using space holder technique. Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction spectroscopy were applied in order to study the morphology, fracture surface and phase compositions of nanopowders and scaffolds. Furthermore, the effects of scaffold composition on the mechanical properties, bioactivity, biodegradability, and cytotoxicity were also evaluated. Results showed that the composite scaffolds with average pore size in the range of 220–310 μm, appearance porosity of 63.1–75.9% and appearance density of 1.1 ± 0.04 g/cm{sup 3} were successfully developed, depending on bredigite content. Indeed, the micropore size of the scaffolds reduced with increasing bredigite content confirming that the sinterability of the scaffolds was improved. Furthermore, the compression strength and modulus of the scaffolds significantly enhanced via incorporation of bredigite content from 0 to 15 wt.%. The composite scaffolds revealed superior bioactivity and biodegradability with increasing bredigite content. Moreover, MTT assay confirmed that HA-15 wt.% bredigite scaffold significantly promoted cell proliferation compared to tissue culture plate (control) and HA scaffold. Based on these results, three-dimensional HA-bredigite scaffolds could be promising replacements for HA scaffolds in bone regeneration. - Highlights: • Nanostructured hydroxyapatite-bredigite composite scaffolds were developed using space holder technique. • Presence of bredigite

Curcumin, an antibiotic resistance breaker against a multiresistant clinical isolate of Mycobacterium abscessus.

Science.gov (United States)

Marini, Emanuela; Di Giulio, Mara; Magi, Gloria; Di Lodovico, Silvia; Cimarelli, Maria Enrica; Brenciani, Andrea; Nostro, Antonia; Cellini, Luigina; Facinelli, Bruna

2018-03-01

Curcumin, a phenolic compound extracted from Curcuma longa, exerts multiple pharmacological effects, including an antimicrobial action. Mycobacterium abscessus, an environmental, nontuberculous, rapidly growing mycobacterium, is an emerging human pathogen causing serious lung infections and one of the most difficult to treat, due to its multidrug resistance and biofilm-forming ability. We wanted to evaluate the antimicrobial and antivirulence activity of curcumin and its ability to synergize with antibiotics against a clinical M. abscessus strain (29904), isolated from the bronchoaspirate of a 66-year-old woman admitted to hospital for suspected tuberculosis. Curcumin [minimum inhibitory concentrations (MIC) = 128 mg/L] was synergic (fractional inhibitory concentration index ≤0.5) with amikacin, clarithromycin, ciprofloxacin, and linezolid, to which strain 29904 showed resistance/intermediate susceptibility. Curcumin at 1/8 × MIC significantly reduced motility, whereas at 4 × MIC, it completely inhibited 4- and 8-day mature biofilms. Synergistic combinations of curcumin and amikacin induced a general reduction in microbial aggregates and substantial loss in cell viability. Disruption of 4- and 8-day biofilms was the main effect detected when curcumin was the predominant compound. The present findings support previous evidence that curcumin is a potential antibiotic resistance breaker. Curcumin, either alone or combined with antibiotics, could provide a novel strategy to combat antibiotic resistance and virulence of M. abscessus. Copyright © 2017 John Wiley & Sons, Ltd.

Opera: reconstructing optimal genomic scaffolds with high-throughput paired-end sequences.

Science.gov (United States)

Gao, Song; Sung, Wing-Kin; Nagarajan, Niranjan

2011-11-01

Scaffolding, the problem of ordering and orienting contigs, typically using paired-end reads, is a crucial step in the assembly of high-quality draft genomes. Even as sequencing technologies and mate-pair protocols have improved significantly, scaffolding programs still rely on heuristics, with no guarantees on the quality of the solution. In this work, we explored the feasibility of an exact solution for scaffolding and present a first tractable solution for this problem (Opera). We also describe a graph contraction procedure that allows the solution to scale to large scaffolding problems and demonstrate this by scaffolding several large real and synthetic datasets. In comparisons with existing scaffolders, Opera simultaneously produced longer and more accurate scaffolds demonstrating the utility of an exact approach. Opera also incorporates an exact quadratic programming formulation to precisely compute gap sizes (Availability: http://sourceforge.net/projects/operasf/ ).

Metacognitive Scaffolding in an Innovative Learning Arrangement

Science.gov (United States)

Molenaar, Inge; van Boxtel, Carla A. M.; Sleegers, Peter J. C.

2011-01-01

This study examined the effects of metacognitive scaffolds on learning outcomes of collaborating students in an innovative learning arrangement. The triads were supported by computerized scaffolds, which were dynamically integrated into the learning process and took a structuring or problematizing form. In an experimental design the two…

Metallic powder-bed based 3D printing of cellular scaffolds for orthopaedic implants: A state-of-the-art review on manufacturing, topological design, mechanical properties and biocompatibility.

Science.gov (United States)

Tan, X P; Tan, Y J; Chow, C S L; Tor, S B; Yeong, W Y

2017-07-01

Metallic cellular scaffold is one of the best choices for orthopaedic implants as a replacement of human body parts, which could improve life quality and increase longevity for the people needed. Unlike conventional methods of making cellular scaffolds, three-dimensional (3D) printing or additive manufacturing opens up new possibilities to fabricate those customisable intricate designs with highly interconnected pores. In the past decade, metallic powder-bed based 3D printing methods emerged and the techniques are becoming increasingly mature recently, where selective laser melting (SLM) and selective electron beam melting (SEBM) are the two representatives. Due to the advantages of good dimensional accuracy, high build resolution, clean build environment, saving materials, high customisability, etc., SLM and SEBM show huge potential in direct customisable manufacturing of metallic cellular scaffolds for orthopaedic implants. Ti-6Al-4V to date is still considered to be the optimal materials for producing orthopaedic implants due to its best combination of biocompatibility, corrosion resistance and mechanical properties. This paper presents a state-of-the-art overview mainly on manufacturing, topological design, mechanical properties and biocompatibility of cellular Ti-6Al-4V scaffolds via SLM and SEBM methods. Current manufacturing limitations, topological shortcomings, uncertainty of biocompatible test were sufficiently discussed herein. Future perspectives and recommendations were given at the end. Copyright © 2017 Elsevier B.V. All rights reserved.

Image-Based Three-Dimensional Analysis to Characterize the Texture of Porous Scaffolds

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Diana Massai

2014-01-01

Full Text Available The aim of the present study is to characterize the microstructure of composite scaffolds for bone tissue regeneration containing different ratios of chitosan/gelatin blend and bioactive glasses. Starting from realistic 3D models of the scaffolds reconstructed from micro-CT images, the level of heterogeneity of scaffold architecture is evaluated performing a lacunarity analysis. The results demonstrate that the presence of the bioactive glass component affects not only macroscopic features such as porosity, but mainly scaffold microarchitecture giving rise to structural heterogeneity, which could have an impact on the local cell-scaffold interaction and scaffold performances. The adopted approach allows to investigate the scale-dependent pore distribution within the scaffold and the related structural heterogeneity features, providing a comprehensive characterization of the scaffold texture.

Osteochondral tissue engineering: scaffolds, stem cells and applications

Science.gov (United States)

Nooeaid, Patcharakamon; Salih, Vehid; Beier, Justus P; Boccaccini, Aldo R

2012-01-01

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment. PMID:22452848

The role of three-dimensional pure bovine gelatin scaffolds in tendon healing, modeling, and remodeling: an in vivo investigation with potential clinical value.

Science.gov (United States)

Oryan, Ahmad; Sharifi, Pardis; Moshiri, Ali; Silver, Ian A

2017-09-01

Large tendon defects involving extensive tissue loss present complex clinical problems. Surgical reconstruction of such injuries is normally performed by transplanting autogenous and allogenous soft tissues that are expected to remodel to mimic a normal tendon. However, the use of grafts has always been associated with significant limitations. Tissue engineering employing artificial scaffolds may provide acceptable alternatives. Gelatin is a hydrolyzed form of collagen that is bioactive, biodegradable, and biocompatible. The present study has investigated the suitability of gelatin scaffold for promoting healing of a large tendon-defect model in rabbits. An experimental model of a large tendon defect was produced by partial excision of the Achilles tendon of the left hind leg in adult rabbits. To standardize and stabilize the length of the tendon defect a modified Kessler core suture was anchored in the sectioned tendon ends. The defects were either left untreated or filled with three-dimensional gelatin scaffold. Before euthanasia 60 days after injury, the progress of healing was evaluated clinically. Samples of healing tendon were harvested at autopsy and evaluated by gross, histopathologic, scanning, and transmission electron microscopy, and by biomechanical testing. The treated animals showed superior weight-bearing and physical activity compared with those untreated, while frequency of peritendinous adhesions around the healing site was reduced. The gelatin scaffold itself was totally degraded and replaced by neo-tendon that morphologically had significantly greater numbers, diameters, density, and maturation of collagen fibrils, fibers, and fiber bundles than untreated tendon scar tissue. It also had mechanically higher ultimate load, yield load, stiffness, maximum stress and elastic modulus, when compared to the untreated tendons. Gelatin scaffold may be a valuable option in surgical reconstruction of large tendon defects.

Ribosomal Antibiotics: Contemporary Challenges

Directory of Open Access Journals (Sweden)

Tamar Auerbach-Nevo

2016-06-01

Full Text Available Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

Antibiotics and Breastfeeding.

Science.gov (United States)

de Sá Del Fiol, Fernando; Barberato-Filho, Silvio; de Cássia Bergamaschi, Cristiane; Lopes, Luciane Cruz; Gauthier, Timothy P

2016-01-01

During the breastfeeding period, bacterial infections can occur in the nursing mother, requiring the use of antibiotics. A lack of accurate information may lead health care professionals and mothers to suspend breastfeeding, which may be unnecessary. This article provides information on the main antibiotics that are appropriate for clinical use and the interference of these antibiotics with the infant to support medical decisions regarding the discontinuation of breastfeeding. We aim to provide information on the pharmacokinetic factors that interfere with the passage of antibiotics into breast milk and the toxicological implications of absorption by the infant. Publications related to the 20 most frequently employed antibiotics and their transfer into breast milk were evaluated. The results demonstrate that most antibiotics in clinical use are considered suitable during breastfeeding; however, the pharmacokinetic profile of each drug must be observed to ensure the resolution of the maternal infection and the safety of the infant. © 2016 S. Karger AG, Basel.

Comparative outcomes of β-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches.

Science.gov (United States)

Lee, Boeun; Tam, Idy; Weigel, Bernard; Breeze, Janis L; Paulus, Jessica K; Nelson, Jason; Allison, Genève M

2015-08-01

β-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with β-lactam antibiotics as OPAT. We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug. Four hundred patients were identified (cefazolin n = 38, ceftriaxone n = 104, ertapenem n = 128 and oxacillin n = 130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; P antibiotic switches were accomplished without readmission. Adverse drug events (ADEs) were the most common reason for outpatient antibiotic switches (31/37, 84%). The ADE rate was higher for the oxacillin group (cefazolin 2.0 versus ceftriaxone 1.5 versus ertapenem 2.9 versus oxacillin 8.4 per 1000 OPAT days; P antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Crosslinked pullulan/cellulose acetate fibrous scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Atila, Deniz [Department of Engineering Sciences, Middle East Technical University (Turkey); Keskin, Dilek [Department of Engineering Sciences, Middle East Technical University (Turkey); Biomaterials and Tissue Engineering Center of Excellence, Middle East Technical University (Turkey); Tezcaner, Ayşen, E-mail: tezcaner@metu.edu.tr [Department of Engineering Sciences, Middle East Technical University (Turkey); Biomaterials and Tissue Engineering Center of Excellence, Middle East Technical University (Turkey)

2016-12-01

Natural polymer based fibrous scaffolds have been explored for bone tissue engineering applications; however, their inadequate 3-dimensionality and poor mechanical properties are among the concerns for their use as bone substitutes. In this study, pullulan (P) and cellulose acetate (CA), two polysaccharides, were electrospun at various P/CA ratios (P{sub 80}/CA{sub 20}, P{sub 50}/CA{sub 50}, and P{sub 20}/CA{sub 80}%) to develop 3D fibrous network. The scaffolds were then crosslinked with trisodium trimetaphosphate (STMP) to improve the mechanical properties and to delay fast weight loss. The lowest weight loss was observed for the groups that were crosslinked with P/STMP 2/1 for 10 min. Fiber morphologies of P{sub 50}/CA{sub 50} were more uniform without phase separation and this group was crosslinked most efficiently among groups. It was found that mechanical properties of P{sub 20}/CA{sub 80} and P{sub 50}/CA{sub 50} were higher than that of P{sub 80}/CA{sub 20.} After crosslinking strain values of P{sub 50}/CA{sub 50} scaffolds were improved and these scaffolds became more stable. Unlike P{sub 80}/CA{sub 20,} uncrosslinked P{sub 50}/CA{sub 50} and P{sub 20}/CA{sub 80} were not lost in PBS. Among all groups, crosslinked P{sub 50}/CA{sub 50} scaffolds had more uniform pores; therefore this group was used for bioactivity and cell culture studies. Apatite-like structures were observed on fibers after SBF incubation. Human Osteogenic Sarcoma Cell Line (Saos-2) seeded onto crosslinked P{sub 50}/CA{sub 50} scaffolds adhered and proliferated. The functionality of cells was tested by measuring ALP activity of the cells and the results indicated their osteoblastic differentiation. In vitro tests showed that scaffolds were cytocompatible. To sum up, crosslinked P{sub 50}/CA{sub 50} scaffolds were proposed as candidate cell carriers for bone tissue engineering applications. - Highlights: • Crosslinked 3D electrospun P/CA scaffolds were prepared for the first time. • CA

Magnesium Oxide Nanoparticles Reinforced Electrospun Alginate-Based Nanofibrous Scaffolds with Improved Physical Properties

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R. T. De Silva

2017-01-01

Full Text Available Mechanically robust alginate-based nanofibrous scaffolds were successfully fabricated by electrospinning method to mimic the natural extracellular matrix structure which benefits development and regeneration of tissues. Alginate-based nanofibres were electrospun from an alginate/poly(vinyl alcohol (PVA polyelectrolyte complex. SEM images revealed the spinnability of the complex composite nanofibrous scaffolds, showing randomly oriented, ultrafine, and virtually defects-free alginate-based/MgO nanofibrous scaffolds. Here, it is shown that an alginate/PVA complex scaffold, blended with near-spherical MgO nanoparticles (⌀ 45 nm at a predetermined concentration (10% (w/w, is electrospinnable to produce a complex composite nanofibrous scaffold with enhanced mechanical stability. For the comparison purpose, chemically cross-linked electrospun alginate-based scaffolds were also fabricated. Tensile test to rupture revealed the significant differences in the tensile strength and elastic modulus among the alginate scaffolds, alginate/MgO scaffolds, and cross-linked alginate scaffolds (P<0.05. In contrast to cross-linked alginate scaffolds, alginate/MgO scaffolds yielded the highest tensile strength and elastic modulus while preserving the interfibre porosity of the scaffolds. According to the thermogravimetric analysis, MgO reinforced alginate nanofibrous scaffolds exhibited improved thermal stability. These novel alginate-based/MgO scaffolds are economical and versatile and may be further optimised for use as extracellular matrix substitutes for repair and regeneration of tissues.

SCAFFOLDING TUTORING STRATEGY ON VIRTUAL ENVIRONMENTS FOR TRAINING SCAFFOLDING COMO ESTRATEGIA DE TUTORIA EN ENTORNOS VIRTUALES DE ENTRENAMIENTO

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Angélica de Antonio Jiménez

2008-06-01

Full Text Available Because the conversational capabilities of pedagogical agents (embodiments of trainers allow social interactions with learner(s, their application in 3D virtual environments for training, besides improving the interaction and giving more realism to virtual training, permits changes in tutoring strategies bringing closer the virtual experience to the real one. Scaffolding emerges from the work of some famous educators as an instructional paradigm and it is becoming more and more used in computer-based education. Of course, scaffolding application on virtual environments for trainings is very different from its original conception, and its application in a classroom. Virtual environments for training features, the pedagogical agent embodiment, and its possibilities of virtual interaction make possible the use of this strategy characterized by its adjustment to learner's performance and its dynamic use of work tools, among others. This article explores the advantages of using scaffolding on virtual environments for training as a tutoring strategy for pedagogical agents, focusing on the key features of scaffolding and how they can be applied in pedagogical activities. Activity Theory as well as roles and reusable learning objects design by contract are used to model our proposal. Finally, one procedure to apply scaffolding as a tutoring strategy for pedagogical agents in virtual environment for training designed using the "Model for Application of Intelligent Virtual Environments to Formation" is proposed.Las capacidades conversacionales de un agente pedagógico (la personificación del entrenador permiten una interacción social con los aprendices; luego, su aplicación en entornos virtuales 3D para el entrenamiento permite mejorar esta interacción y da mayor realismo al entrenamiento virtual, permitiendo cambios en las estrategias de tutorías que acercan la experiencia virtual a una real. Scaffolding emerge del trabajo de famosos educadores como

The maturation of cortical sleep rhythms and networks over early development.

Science.gov (United States)

Chu, C J; Leahy, J; Pathmanathan, J; Kramer, M A; Cash, S S

2014-07-01

Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

An improved polymeric sponge replication method for biomedical porous titanium scaffolds

Energy Technology Data Exchange (ETDEWEB)

Wang, Chunli; Chen, Hongjie; Zhu, Xiangdong, E-mail: zxd7303@163.com; Xiao, Zhanwen; Zhang, Kai, E-mail: kaizhang@scu.edu.cn; Zhang, Xingdong

2017-01-01

Biomedical porous titanium (Ti) scaffolds were fabricated by an improved polymeric sponge replication method. The unique formulations and distinct processing techniques, i.e. a mixture of water and ethanol as solvent, multiple coatings with different viscosities of the Ti slurries and centrifugation for removing the extra slurries were used in the present study. The optimized porous Ti scaffolds had uniform porous structure and completely interconnected macropores (~ 365.1 μm). In addition, two different sizes of micropores (~ 45.4 and ~ 6.2 μm) were also formed in the skeleton of the scaffold. The addition of ethanol to the Ti slurry increased the compressive strength of the scaffold by improving the compactness of the skeleton. A compressive strength of 83.6 ± 4.0 MPa was achieved for a porous Ti scaffold with a porosity of 66.4 ± 1.8%. Our cellular study also revealed that the scaffolds could support the growth and proliferation of mesenchymal stem cells (MSCs). - Highlights: • An improved sponge replication method for porous titanium scaffolds was developed. • A mixture of water and ethanol was used to make the titanium slurries. • The scaffolds have high mechanical strength for load-bearing bone repair. • The scaffolds support growth of mesenchymal stem cells.

Antibiotics: Miracle Drugs

Centers for Disease Control (CDC) Podcasts

The overuse of antibiotics has led to the development of resistance among bacteria, making antibiotics ineffective in treating certain conditions. This podcast discusses the importance of talking to your healthcare professional about whether or not antibiotics will be beneficial if you've been diagnosed with an infectious disease.

Antibiotics: Miracle Drugs

Centers for Disease Control (CDC) Podcasts

2015-04-16

The overuse of antibiotics has led to the development of resistance among bacteria, making antibiotics ineffective in treating certain conditions. This podcast discusses the importance of talking to your healthcare professional about whether or not antibiotics will be beneficial if you’ve been diagnosed with an infectious disease.  Created: 4/16/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

In vitro evaluation of alginate/halloysite nanotube composite scaffolds for tissue engineering

International Nuclear Information System (INIS)

Liu, Mingxian; Dai, Libing; Shi, Huizhe; Xiong, Sheng; Zhou, Changren

2015-01-01

In this study, a series of alginate/halloysite nanotube (HNTs) composite scaffolds were prepared by solution-mixing and freeze-drying method. HNTs are incorporated into alginate to improve both the mechanical and cell-attachment properties of the scaffolds. The interfacial interactions between alginate and HNTs were confirmed by the atomic force microscope (AFM), transmission electron microscope (TEM) and FTIR spectroscopy. The mechanical, morphological, and physico-chemical properties of the composite scaffolds were investigated. The composite scaffolds exhibit significant enhancement in compressive strength and compressive modulus compared with pure alginate scaffold both in dry and wet states. A well-interconnected porous structure with size in the range of 100–200 μm and over 96% porosity is found in the composite scaffolds. X-ray diffraction (XRD) result shows that HNTs are uniformly dispersed and partly oriented in the composite scaffolds. The incorporation of HNTs leads to increase in the scaffold density and decrease in the water swelling ratio of alginate. HNTs improve the stability of alginate scaffolds against enzymatic degradation in PBS solution. Thermogravimetrica analysis (TGA) shows that HNTs can improve the thermal stability of the alginate. The mouse fibroblast cells display better attachment to the alginate/HNT composite than those to the pure alginate, suggesting the good cytocompatibility of the composite scaffolds. Alginate/HNT composite scaffolds exhibit great potential for applications in tissue engineering. - Highlights: • We fabricated HNTs reinforced alginate composite scaffolds for biomedical applications. • The hydrogen bond interactions between HNTs and alginate are confirmed. • HNTs can significantly enhance the mechanical properties of alginate scaffold. • The scaffolds exhibit a highly porous structure with interconnected pores. • HNTs can improve the cell attachment and proliferation on alginate

In vitro evaluation of alginate/halloysite nanotube composite scaffolds for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Liu, Mingxian [Department of Materials Science and Engineering, Jinan University, Guangzhou 510632 (China); Dai, Libing [Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital Medical College, Jinan University, Guangzhou 510220 (China); Shi, Huizhe; Xiong, Sheng [Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632 (China); Zhou, Changren, E-mail: tcrz9@jnu.edu.cn [Department of Materials Science and Engineering, Jinan University, Guangzhou 510632 (China)

2015-04-01

In this study, a series of alginate/halloysite nanotube (HNTs) composite scaffolds were prepared by solution-mixing and freeze-drying method. HNTs are incorporated into alginate to improve both the mechanical and cell-attachment properties of the scaffolds. The interfacial interactions between alginate and HNTs were confirmed by the atomic force microscope (AFM), transmission electron microscope (TEM) and FTIR spectroscopy. The mechanical, morphological, and physico-chemical properties of the composite scaffolds were investigated. The composite scaffolds exhibit significant enhancement in compressive strength and compressive modulus compared with pure alginate scaffold both in dry and wet states. A well-interconnected porous structure with size in the range of 100–200 μm and over 96% porosity is found in the composite scaffolds. X-ray diffraction (XRD) result shows that HNTs are uniformly dispersed and partly oriented in the composite scaffolds. The incorporation of HNTs leads to increase in the scaffold density and decrease in the water swelling ratio of alginate. HNTs improve the stability of alginate scaffolds against enzymatic degradation in PBS solution. Thermogravimetrica analysis (TGA) shows that HNTs can improve the thermal stability of the alginate. The mouse fibroblast cells display better attachment to the alginate/HNT composite than those to the pure alginate, suggesting the good cytocompatibility of the composite scaffolds. Alginate/HNT composite scaffolds exhibit great potential for applications in tissue engineering. - Highlights: • We fabricated HNTs reinforced alginate composite scaffolds for biomedical applications. • The hydrogen bond interactions between HNTs and alginate are confirmed. • HNTs can significantly enhance the mechanical properties of alginate scaffold. • The scaffolds exhibit a highly porous structure with interconnected pores. • HNTs can improve the cell attachment and proliferation on alginate.

3D-printed bioceramic scaffolds with antibacterial and osteogenic activity.

Science.gov (United States)

Zhang, Yongliang; Zhai, Dong; Xu, Mengchi; Yao, Qingqiang; Zhu, Huiying; Chang, Jiang; Wu, Chengtie

2017-06-20

Bacterial infection poses a significant risk with the wide application of bone graft materials. Designing bone grafts with good antibacterial performance and excellent bone-forming activity is of particular significance for bone tissue engineering. In our study, a 3D printing method was used to prepare β-tricalcium phosphate (β-TCP) bioceramic scaffolds. Silver (Ag) nanoparticles were uniformly dispersed on graphene oxide (GO) to form a homogeneous nanocomposite (named Ag@GO) with different Ag-to-graphene oxide mass ratios, with this being synthesized via the liquid chemical reduction approach. Ag@GO nanocomposites were successfully modified on the β-TCP scaffolds by a simple soaking method to achieve bifunctional biomaterials with antibacterial and osteogenic activity. The prepared scaffolds possessed a connected network with triangle pore morphology and the surfaces of the β-TCP scaffolds were uniformly modified by the Ag@GO nanocomposite layers. The Ag content in the scaffolds was controlled by changing the coating times and concentration of the Ag@GO nanocomposites. The antibacterial activity of the scaffolds was assessed with Gram-negative bacteria (Escherichia coli, E. coli). The results demonstrated that the scaffolds with Ag@GO nanocomposites presented excellent antibacterial activity. In addition, the scaffolds coated with Ag@GO nanocomposites conspicuously accelerated the osteogenic differentiation of rabbit bone marrow stromal cells by improving their alkaline phosphatase activity and bone-related gene expression (osteopontin, runt-related transcription factor 2, osteocalcin and bone sialoprotein). This study demonstrates that bifunctional scaffolds with a combination of antibacterial and osteogenic activity can be achieved for the reconstruction of large-bone defects while preventing or treating infections.

Three-Dimensional Printing of Hollow-Struts-Packed Bioceramic Scaffolds for Bone Regeneration.

Science.gov (United States)

Luo, Yongxiang; Zhai, Dong; Huan, Zhiguang; Zhu, Haibo; Xia, Lunguo; Chang, Jiang; Wu, Chengtie

2015-11-04

Three-dimensional printing technologies have shown distinct advantages to create porous scaffolds with designed macropores for application in bone tissue engineering. However, until now, 3D-printed bioceramic scaffolds only possessing a single type of macropore have been reported. Generally, those scaffolds with a single type of macropore have relatively low porosity and pore surfaces, limited delivery of oxygen and nutrition to surviving cells, and new bone tissue formation in the center of the scaffolds. Therefore, in this work, we present a useful and facile method for preparing hollow-struts-packed (HSP) bioceramic scaffolds with designed macropores and multioriented hollow channels via a modified coaxial 3D printing strategy. The prepared HSP scaffolds combined high porosity and surface area with impressive mechanical strength. The unique hollow-struts structures of bioceramic scaffolds significantly improved cell attachment and proliferation and further promoted formation of new bone tissue in the center of the scaffolds, indicating that HSP ceramic scaffolds can be used for regeneration of large bone defects. In addition, the strategy can be used to prepare other HSP ceramic scaffolds, indicating a universal application for tissue engineering, mechanical engineering, catalysis, and environmental materials.

Incentives for new antibiotics: the Options Market for Antibiotics (OMA) model.

Science.gov (United States)

Brogan, David M; Mossialos, Elias

2013-11-07

Antimicrobial resistance is a growing threat resulting from the convergence of biological, economic and political pressures. Investment in research and development of new antimicrobials has suffered secondary to these pressures, leading to an emerging crisis in antibiotic resistance. Current policies to stimulate antibiotic development have proven inadequate to overcome market failures. Therefore innovative ideas utilizing market forces are necessary to stimulate new investment efforts. Employing the benefits of both the previously described Advanced Market Commitment and a refined Call Options for Vaccines model, we describe herein a novel incentive mechanism, the Options Market for Antibiotics. This model applies the benefits of a financial call option to the investment in and purchase of new antibiotics. The goal of this new model is to provide an effective mechanism for early investment and risk sharing while maintaining a credible purchase commitment and incentives for companies to ultimately bring new antibiotics to market. We believe that the Options Market for Antibiotics (OMA) may help to overcome some of the traditional market failures associated with the development of new antibiotics. Additional work must be done to develop a more robust mathematical model to pave the way for practical implementation.

Bone regeneration in critical bone defects using three-dimensionally printed β-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2.

Science.gov (United States)

Ishack, Stephanie; Mediero, Aranzazu; Wilder, Tuere; Ricci, John L; Cronstein, Bruce N

2017-02-01

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3D) printing technology we have created custom 3D scaffolds of hydroxyapatite (HA)/beta-tri-calcium phosphate (β-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. Nearly 15% HA:85% β-TCP scaffolds were designed using Robocad software, fabricated using a 3D Robocasting system, and sintered at 1100°C for 4 h. Scaffolds were coated with BMP-2 (200 ng mL -1 ), dypiridamole 100 µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3 mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. Micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/β-TCP-dipyridamole and HA/β-TCP-BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4, and 8 weeks (n = 5 per group; p ≤ 0.05, p ≤ 0.05, and p ≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/β-TCP- dipyridamole and HA/β-TCP-BMP-2 scaffolds. Coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/β-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 366-375, 2017. © 2015 Wiley Periodicals, Inc.

Scaffolding students’ assignments

DEFF Research Database (Denmark)

Slot, Marie Falkesgaard

2013-01-01

This article discusses scaffolding in typical student assignments in mother tongue learning materials in upper secondary education in Denmark and the United Kingdom. It has been determined that assignments do not have sufficient scaffolding end features to help pupils understand concepts and build...... objects. The article presents the results of empirical research on tasks given in Danish and British learning materials. This work is based on a further development of my PhD thesis: “Learning materials in the subject of Danish” (Slot 2010). The main focus is how cognitive models (and subsidiary explicit...... learning goals) can help students structure their argumentative and communica-tive learning processes, and how various multimodal representations can give more open-ended learning possibilities for collaboration. The article presents a short introduction of the skills for 21st century learning and defines...

Biologically inspired growth of hydroxyapatite crystals on bio-organics-defined scaffolds

Energy Technology Data Exchange (ETDEWEB)

Yang, Chunrong, E-mail: milkhoney3@163.com [Department of Materials Science and Engineering, Fujian University of Technology, Fuzhou 350108 (China); Li, Yuli; Nan, Kaihui [Eye Hospital, Wenzhou Medical College, Wenzhou 325027 (China)

2013-03-15

Graphical abstract: Petal-like crystals were observed to form on the surface of the BG/COL/ChS scaffolds. Highlights: ► Porous scaffolds were prepared using bioglass, collagen and chondroitin sulfate. ► Highly oriented HA crystals were grown on scaffolds using simulated body fluids ► The microstructure and orientation of HA were explained by molecular configuration. - Abstract: Several bio-organics-defined composite scaffolds were prepared using 58s-bioglass (BG), collagen (Col) and chondroitin sulfate (ChS). These scaffolds possess highly porous structure. X-ray diffraction of these scaffolds strongly indicated that hydroxyapatite (HA) crystals formed on their surfaces in simulated body fluids within 3 d, and similar formation process of crystals could be obtained on BG/Col and BG/Col/ChS scaffolds. The morphology and structure of the crystals were further examined by scanning electron microscopy. The results obtained indicate that an apatite with petal-like structure similar to that found on BG/Col scaffolds can be produced on BG/Col/ChS scaffolds through biomimetic synthesis, while that on BG/ChS scaffolds took place differently. The differences could be explained by self-assembly processes and the different macromolecular configurations of the Col and ChS fibrils which self-assemble spontaneously into their fibers. On the other hand, the bio-organics-defined composites have good cell biocompability. The results may be applicable to develop tailored biomaterials for peculiar bone substitute.

Biologically inspired growth of hydroxyapatite crystals on bio-organics-defined scaffolds

International Nuclear Information System (INIS)

Yang, Chunrong; Li, Yuli; Nan, Kaihui

2013-01-01

Graphical abstract: Petal-like crystals were observed to form on the surface of the BG/COL/ChS scaffolds. Highlights: ► Porous scaffolds were prepared using bioglass, collagen and chondroitin sulfate. ► Highly oriented HA crystals were grown on scaffolds using simulated body fluids ► The microstructure and orientation of HA were explained by molecular configuration. - Abstract: Several bio-organics-defined composite scaffolds were prepared using 58s-bioglass (BG), collagen (Col) and chondroitin sulfate (ChS). These scaffolds possess highly porous structure. X-ray diffraction of these scaffolds strongly indicated that hydroxyapatite (HA) crystals formed on their surfaces in simulated body fluids within 3 d, and similar formation process of crystals could be obtained on BG/Col and BG/Col/ChS scaffolds. The morphology and structure of the crystals were further examined by scanning electron microscopy. The results obtained indicate that an apatite with petal-like structure similar to that found on BG/Col scaffolds can be produced on BG/Col/ChS scaffolds through biomimetic synthesis, while that on BG/ChS scaffolds took place differently. The differences could be explained by self-assembly processes and the different macromolecular configurations of the Col and ChS fibrils which self-assemble spontaneously into their fibers. On the other hand, the bio-organics-defined composites have good cell biocompability. The results may be applicable to develop tailored biomaterials for peculiar bone substitute

Three-dimensional electrospun polycaprolactone (PCL)/alginate hybrid composite scaffolds.

Science.gov (United States)

Kim, Min Seong; Kim, GeunHyung

2014-12-19

Micro/nanofibrous scaffolds have been used widely in biomedical applications because the micro/nano-scale fibres resemble natural extracellular matrix and the high surface-to-volume ratio encourages cellular activities (attachment and proliferation). However, poor mechanical properties, low controllability of various shapes and difficulties in obtaining controllable pore structure have been obstacles to their use in hard-tissue regeneration. To overcome these shortcomings, we suggest a new composite system, which uses a combination method of wet electrospinning, rapid prototyping and a physical punching process. Using the process, we obtained polycaprolactone (PCL)/alginate composite scaffolds, consisting of electrospun PCL/alginate fibres and micro-sized PCL struts, with mean pore sizes of 821 ± 55 μm. To show the feasibility of the scaffolds for hard-tissue regeneration, the scaffolds were assessed not only for physical properties, including hydrophilicity, water absorption, and tensile and compressive strength, but also in vitro cellular responses (cell viability and proliferation) and osteogenic differentiation (alkaline phosphatase (ALP) activity, and mineralisation) by culturing with pre-osteoblasts (MC3T3-E1 cells). With the reinforcing micro-sized PCL struts, the elastic modulus of the PCL/alginate scaffold was significantly improved versus a pure PCL scaffold. Additionally, due to the alginate component in the fibrous scaffold, they showed significantly enhanced hydrophilic behaviour, water absorption (∼8-fold) and significant biological activities (∼1.6-fold for cell viability at 7 days, ∼2.3-fold for ALP activity at 14 days and ∼6.4-fold for calcium mineralisation at 14 days) compared with those of a pure PCL fibrous scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix

Energy Technology Data Exchange (ETDEWEB)

Cholas, Rahmatullah, E-mail: rahmat.cholas@gmail.com; Kunjalukkal Padmanabhan, Sanosh, E-mail: sanosh2001@gmail.com; Gervaso, Francesca; Udayan, Gayatri; Monaco, Graziana; Sannino, Alessandro; Licciulli, Antonio

2016-06-01

Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6 μm, a specific surface area of 40 m{sup 2}/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16 nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200 μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15 days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales. - Highlights: • Mesoporous hydroxyapatite microsphere(mHA) synthesized by spray drying method • Porous collagen/mHA composite scaffold made by freeze

Scaffolding Mathematical Modelling with a Solution Plan

Science.gov (United States)

Schukajlow, Stanislaw; Kolter, Jana; Blum, Werner

2015-01-01

In the study presented in this paper, we examined the possibility to scaffold mathematical modelling with strategies. The strategies were prompted using an instrument called "solution plan" as a scaffold. The effects of this step by step instrument on mathematical modelling competency and on self-reported strategies were tested using…

Fabrication of chitosan/gallic acid 3D microporous scaffold for tissue engineering applications.

Science.gov (United States)

Thangavel, Ponrasu; Ramachandran, Balaji; Muthuvijayan, Vignesh

2016-05-01

This study explores the potential of gallic acid incorporated chitosan (CS/GA) 3D scaffolds for tissue engineering applications. Scaffolds were prepared by freezing and lyophilization technique and characterized. FTIR spectra confirmed the presence of GA in chitosan (CS) gel. DSC and TGA analysis revealed that the structure of chitosan was not altered due to the incorporation of GA, but thermal stability was significantly increased compared to the CS scaffold. SEM micrographs showed smooth, homogeneous, and microporous architecture of the scaffolds with good interconnectivity. CS/GA scaffolds exhibited approximately 90% porosity on average, increased swelling (600-900%) and controlled biodegradation (15-40%) in PBS (pH 7.4 at 37°C) with 1 mg/mL of lysozyme. CS/GA scaffolds showed 2-4 fold decrease in CFUs (p < 0.05) for both gram positive and gram negative bacteria compared to the CS scaffold. Cytotoxicity of these scaffolds was evaluated using NIH 3T3 L1 fibroblast cells. CS/GA 0.25% scaffold showed similar viability with CS scaffold at 24 and 48 h. CS/GA scaffolds (0.5-1.0%) showed 60-75% viability at 24 h and 90% at 48 h. SEM images showed that an increased cell attachment was observed for CS/GA scaffolds compared to CS scaffolds. These findings authenticate that CS/GA scaffolds were cytocompatible and would be useful for tissue engineering applications. © 2015 Wiley Periodicals, Inc.

Online Process Scaffolding and Students' Self-Regulated Learning with Hypermedia.

Science.gov (United States)

Azevedo, Roger; Cromley, Jennifer G.; Thomas, Leslie; Seibert, Diane; Tron, Myriam

This study examined the role of different scaffolding instructional interventions in facilitating students' shift to more sophisticated mental models as indicated by both performance and process data. Undergraduate students (n=53) were randomly assigned to 1 of 3 scaffolding conditions (adaptive content and process scaffolding (ACPS), adaptive…

Super dielectric capacitor using scaffold dielectric

OpenAIRE

Phillips, Jonathan

2018-01-01

Patent A capacitor having first and second electrodes and a scaffold dielectric. The scaffold dielectric comprises an insulating material with a plurality of longitudinal channels extending across the dielectric and filled with a liquid comprising cations and anions. The plurality of longitudinal channels are substantially parallel and the liquid within the longitudinal channels generally has an ionic strength of at least 0.1. Capacitance results from the migrations of...

PHBV/PAM scaffolds with local oriented structure through UV polymerization for tissue engineering.

Science.gov (United States)

Ke, Yu; Wu, Gang; Wang, Yingjun

2014-01-01

Locally oriented tissue engineering scaffolds can provoke cellular orientation and direct cell spread and migration, offering an exciting potential way for the regeneration of the complex tissue. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds with locally oriented hydrophilic polyacrylamide (PAM) inside the macropores of the scaffolds were achieved through UV graft polymerization. The interpenetrating PAM chains enabled good interconnectivity of PHBV/PAM scaffolds that presented a lower porosity and minor diameter of pores than PHBV scaffolds. The pores with diameter below 100  μm increased to 82.15% of PHBV/PAM scaffolds compared with 31.5% of PHBV scaffolds. PHBV/PAM scaffold showed a much higher compressive elastic modulus than PHBV scaffold due to PAM stuffing. At 5 days of culturing, sheep chondrocytes spread along the similar direction in the macropores of PHBV/PAM scaffolds. The locally oriented PAM chains might guide the attachment and spreading of chondrocytes and direct the formation of microfilaments via contact guidance.

PCL-coated hydroxyapatite scaffold derived from cuttlefish bone: In vitro cell culture studies

International Nuclear Information System (INIS)

Milovac, Dajana; Gamboa-Martínez, Tatiana C.; Ivankovic, Marica; Gallego Ferrer, Gloria; Ivankovic, Hrvoje

2014-01-01

In the present study, we examined the potential of using highly porous poly(ε-caprolactone) (PCL)-coated hydroxyapatite (HAp) scaffold derived from cuttlefish bone for bone tissue engineering applications. The cell culture studies were performed in vitro with preosteoblastic MC3T3-E1 cells in static culture conditions. Comparisons were made with uncoated HAp scaffold. The attachment and spreading of preosteoblasts on scaffolds were observed by Live/Dead staining Kit. The cells grown on the HAp/PCL composite scaffold exhibited greater spreading than cells grown on the HAp scaffold. DNA quantification and scanning electron microscopy (SEM) confirmed a good proliferation of cells on the scaffolds. DNA content on the HAp/PCL scaffold was significantly higher compared to porous HAp scaffolds. The amount of collagen synthesis was determined using a hydroxyproline assay. The osteoblastic differentiation of the cells was evaluated by determining alkaline phosphatase (ALP) activity and collagen type I secretion. Furthermore, cell spreading and cell proliferation within scaffolds were observed using a fluorescence microscope. - Highlights: • Hydroxyapatite/poly(ε-caprolactone) scaffold with interconnected pores was prepared • Cytotoxicity test showed that the scaffold was not cytotoxic towards MC3T3-E1 cells • The scaffold supported the attachment, proliferation and differentiation of cells • A 3D cell colonization was confirmed using the fluorescence microscopy • The scaffold might be a promising candidate for bone tissue engineering

Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair

Energy Technology Data Exchange (ETDEWEB)

Wang, Jianhua; Yang, Qiu; Cheng, Niangmei [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Tao, Xiaojun [Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, Hunan (China); Zhang, Zhihua; Sun, Xiaomin [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Zhang, Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Key Laboratory of Biomedical Materials of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192 (China)

2016-04-01

For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration. - Highlights: • Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere proposed for cartilage repair was created. • In vivo, scaffold could enhance cartilage regeneration and integration between the repaired and surrounding cartilage. • In vitro, scaffold exhibits excellent characteristics, such as, improved porosity water absorption and good cell affinity.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Doğan, Ayşegül; Demirci, Selami [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey); Bayir, Yasin [Department of Biochemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Halici, Zekai [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karakus, Emre [Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum (Turkey); Aydin, Ali [Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Cadirci, Elif [Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Albayrak, Abdulmecit [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Demirci, Elif [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karaman, Adem [Department of Radiology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Ayan, Arif Kursat [Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Gundogdu, Cemal [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Şahin, Fikrettin, E-mail: fsahin@yeditepe.edu.tr [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey)

2014-11-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Doğan, Ayşegül; Demirci, Selami; Bayir, Yasin; Halici, Zekai; Karakus, Emre; Aydin, Ali; Cadirci, Elif; Albayrak, Abdulmecit; Demirci, Elif; Karaman, Adem; Ayan, Arif Kursat; Gundogdu, Cemal; Şahin, Fikrettin

2014-01-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing

29 CFR 1915.71 - Scaffolds or staging.

Science.gov (United States)

2010-07-01

... construction of scaffolds shall be spruce, fir, long leaf yellow pine, Oregon pine or wood of equal strength... large, loose or dead knots. It shall also be free from dry rot, large checks, worm holes or other... accidentally disengaged from the crane hook. (c) Independent pole wood scaffolds. (1) All pole uprights shall...

Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications

International Nuclear Information System (INIS)

Sell, Scott A; Garg, Koyal; McClure, Michael J; Bowlin, Gary L; Francis, Michael P; Simpson, David G

2008-01-01

The purpose of this study was to enhance the mechanical properties and slow the degradation of an electrospun fibrinogen scaffold, while maintaining the scaffold's high level of bioactivity. Three different cross-linkers were used to achieve this goal: glutaraldehyde vapour, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in ethanol and genipin in ethanol. Scaffolds with a fibrinogen concentration of 120 mg ml -1 were electrospun and cross-linked with one of the aforementioned cross-linkers. Mechanical properties were determined through uniaxial tensile testing performed on scaffolds incubated under standard culture conditions for 1 day, 7 days and 14 days. Cross-linked scaffolds were seeded with human foreskin fibroblasts (BJ-GFP-hTERT) and cultured for 7, 14 and 21 days, with histology and scanning electron microscopy performed upon completion of the time course. Mechanical testing revealed significantly increased peak stress and modulus values for the EDC and genipin cross-linked scaffolds, with significantly slowed degradation. However, cross-linking with EDC and genipin was shown to have some negative effect on the bioactivity of the scaffolds as cell migration throughout the thickness of the scaffold was slowed.

Strategies to Minimize Antibiotic Resistance

Directory of Open Access Journals (Sweden)

Sang Hee Lee

2013-09-01

Full Text Available Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs and various data such as pharmacokinetic (PK and pharmacodynamic (PD properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST, clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care, the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing. The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.

Electrospinning versus knitting: two scaffolds for tisssue engineering of the aortic valve

NARCIS (Netherlands)

Lieshout, van M.I.; Vaz, C.M.; Rutten, M.C.M.; Peters, G.W.M.; Baaijens, F.P.T.

2006-01-01

Two types of scaffolds were developed for tissue engineering of the aortic valve; an electrospun valvular scaffold and a knitted valvular scaffold. These scaffolds were compared in a physiologic flow system and in a tissue-engineering process. In fibrin gel enclosed human myofibroblasts were seeded

PEDOT:PSS-Containing Nanohydroxyapatite/Chitosan Conductive Bionanocomposite Scaffold: Fabrication and Evaluation

Directory of Open Access Journals (Sweden)

Alireza Lari

2016-01-01

Full Text Available Conductive poly(3,4-ethylenedioxythiophene-poly(4-styrene sulfonate (PEDOT:PSS was incorporated into nanohydroxyapatite/chitosan (nHA/CS composite scaffolds through a freezing and lyophilization technique. The bionanocomposite conductive scaffold was then characterized using several techniques. A scanning electron microscope image showed that the nHA and PEDOT:PSS were dispersed homogeneously in the chitosan matrix, which was also confirmed by energy-dispersive X-ray (EDX analysis. The conductive properties were measured using a digital multimeter. The weight loss and water-uptake properties of the bionanocomposite scaffolds were studied in vitro. An in vitro cell cytotoxicity test was carried out using mouse fibroblast (L929 cells cultured onto the scaffolds. Using a freezing and lyophilization technique, it was possible to fabricate three-dimensional, highly porous, and interconnected PEDOT:PSS/nHA/CS scaffolds with good handling properties. The porosity was 74% and the scaffold’s conductivity was 9.72±0.78 μS. The surface roughness was increased with the incorporation of nHA and PEDOT:PSS into the CS scaffold. The compressive mechanical properties increased significantly with the incorporation of nHA but did not change significantly with the incorporation of PEDOT:PSS. The PEDOT:PSS-containing nHA/CS scaffold exhibited significantly higher cell attachment. The PEDOT:PSS/nHA/CS scaffold could be a potential bionanocomposite conductive scaffold for tissue engineering.

Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering

International Nuclear Information System (INIS)

Lee, Ju-Yeon; Choi, Bogyu; Wu, Benjamin; Lee, Min

2013-01-01

Three-dimensional printing (3DP) is a rapid prototyping technique that can create complex 3D structures by inkjet printing of a liquid binder onto powder biomaterials for tissue engineering scaffolds. Direct fabrication of scaffolds from 3DP, however, imposes a limitation on material choices by manufacturing processes. In this study, we report an indirect 3DP approach wherein a positive replica of desired shapes was printed using gelatin particles, and the final scaffold was directly produced from the printed mold. To create patient-specific scaffolds that match precisely to a patient's external contours, we integrated our indirect 3DP technique with imaging technologies and successfully created custom scaffolds mimicking human mandibular condyle using polycaprolactone and chitosan for potential osteochondral tissue engineering. To test the ability of the technique to precisely control the internal morphology of the scaffolds, we created orthogonal interconnected channels within the scaffolds using computer-aided-design models. Because very few biomaterials are truly osteoinductive, we modified inert 3D printed materials with bioactive apatite coating. The feasibility of these scaffolds to support cell growth was investigated using bone marrow stromal cells (BMSC). The BMSCs showed good viability in the scaffolds, and the apatite coating further enhanced cellular spreading and proliferation. This technique may be valuable for complex scaffold fabrication. (paper)

Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering

Science.gov (United States)

Velasco, Marco A.; Narváez-Tovar, Carlos A.; Garzón-Alvarado, Diego A.

2015-01-01

A review about design, manufacture, and mechanobiology of biodegradable scaffolds for bone tissue engineering is given. First, fundamental aspects about bone tissue engineering and considerations related to scaffold design are established. Second, issues related to scaffold biomaterials and manufacturing processes are discussed. Finally, mechanobiology of bone tissue and computational models developed for simulating how bone healing occurs inside a scaffold are described. PMID:25883972

Novel scaffold design with multi-grooved PLA fibers

International Nuclear Information System (INIS)

Chung, Sangwon; King, Martin W; Gamcsik, Mike P

2011-01-01

A novel prototype nonwoven textile structure containing polylactide (PLA) multigrooved fibers has been proposed as a possible scaffold material for superior cell attachment and proliferation. Grooved cross-sectional fibers with larger surface area were obtained by a bi-component spinning system and the complete removal of the sacrificial component was confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and x-ray photon spectroscopy (XPS) analysis. These PLA nonwoven scaffolds containing the grooved fibers exhibited enhanced wettability, greater flexibility and tensile properties, and a larger surface area compared to a traditional PLA nonwoven fabric containing round fibers. To evaluate cellular attachment on the two types of PLA nonwoven scaffolds, NIH 3T3 fibroblasts were cultured for up to 12 days. It was evident that the initial cellular attachment was superior on the scaffold with grooved fibers, which was confirmed by MTT viability assay (p < 0.01) and SEM analysis. In the future, by modulating the size of the grooves on the fibers, such a scaffold material with a large surface area could serve as an alternative matrix for culturing different types of cells.

Multilayer porous UHMWPE scaffolds for bone defects replacement.

Science.gov (United States)

Maksimkin, A V; Senatov, F S; Anisimova, N Yu; Kiselevskiy, M V; Zalepugin, D Yu; Chernyshova, I V; Tilkunova, N A; Kaloshkin, S D

2017-04-01

Reconstruction of the structural integrity of the damaged bone tissue is an urgent problem. UHMWPE may be potentially used for the manufacture of porous implants simulating as closely as possible the porous cancellous bone tissue. But the extremely high molecular weight of the polymer does not allow using traditional methods of foaming. Porous and multilayer UHMWPE scaffolds with nonporous bulk layer and porous layer that mimics cancellous bone architecture were obtained by solid-state mixing, thermopressing and washing in subcritical water. Structural and mechanical properties of the samples were studied. Porous UHMWPE samples were also studied in vitro and in vivo. The pores of UHMWPE scaffold are open and interconnected. Volume porosity of the obtained samples was 79±2%; the pore size range was 80-700μm. Strong connection of the two layers in multilayer UHMWPE scaffolds was observed with decreased number of fusion defects. Functionality of implants based on multilayer UHMWPE scaffolds is provided by the fixation of scaffolds in the bone defect through ingrowths of the connective tissue into the pores, which ensures the maintenance of the animals' mobility. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabrication and characterization of calcium phosphate cement scaffolds

International Nuclear Information System (INIS)

Sousa, E. de; Motisuke, M.; Bertran, C.A.

2011-01-01

In Tissue Engineering, the need for scaffolds which are capable of guiding the organization, differentiation and growth of cells leading to the formation of new tissues is highly relevant. For the development of new scaffolds focused on bone tissue therapy, calcium phosphate cements (CPC) have great potential, because besides their resorbability, they present morphology and chemical composition similar to the bone mineral phase. Moreover, there are several processing techniques to produce ceramic scaffolds: polymeric sponge replication, incorporation of organic material into the ceramic powder, gelcasting, emulsion, among others. The aim of this work was to obtain CPCs scaffolds by using two techniques, emulsion and gelcasting. The scaffolds were characterized by their physical and mechanical properties and the crystalline phases formed after the setting reaction of cement were determined by X-ray diffraction. The samples obtained by both methods presented porosity between 61-65% and the microstructure consists of nearly spherical pores (d5o = 50-100 μm). The mechanical strength of the samples ranged from 5.5 to 1.5 MPa. The crystalline phases found were monetite (CaHPO 4 ) and brushite (CaHPO 4 2H 2 O). (author)

Solvent/Non-Solvent Sintering To Make Microsphere Scaffolds

Science.gov (United States)

Laurencin, Cato T.; Brown, Justin L.; Nair, Lakshmi

2011-01-01

A solvent/non-solvent sintering technique has been devised for joining polymeric microspheres to make porous matrices for use as drug-delivery devices or scaffolds that could be seeded with cells for growing tissues. Unlike traditional sintering at elevated temperature and pressure, this technique is practiced at room temperature and pressure and, therefore, does not cause thermal degradation of any drug, protein, or other biochemical with which the microspheres might be loaded to impart properties desired in a specific application. Also, properties of scaffolds made by this technique are more reproducible than are properties of comparable scaffolds made by traditional sintering. The technique involves the use of two miscible organic liquids: one that is and one that is not a solvent for the affected polymer. The polymeric microspheres are placed in a mold having the size and shape of the desired scaffold, then the solvent/non-solvent mixture is poured into the mold to fill the void volume between the microspheres, then the liquid mixture is allowed to evaporate. Some of the properties of the resulting scaffold can be tailored through choice of the proportions of the liquids and the diameter of the microspheres.

Surface-modified functionalized polycaprolactone scaffolds for bone repair

DEFF Research Database (Denmark)

Jensen, Jonas; Rölfing, Jan Hendrik Duedal; Svend Le, Dang Quang

2014-01-01

A porcine calvaria defect study was carried out to investigate the bone repair potential of three-dimensional (3D)-printed poly-ε-caprolactone (PCL) scaffolds embedded with nanoporous PCL. A microscopic grid network was created by rapid prototyping making a 3D-fused deposition model (FDM-PCL). Af......A porcine calvaria defect study was carried out to investigate the bone repair potential of three-dimensional (3D)-printed poly-ε-caprolactone (PCL) scaffolds embedded with nanoporous PCL. A microscopic grid network was created by rapid prototyping making a 3D-fused deposition model (FDM......-PCL). Afterward, the FDM-PCL scaffolds were infused with a mixture of PCL, water, and 1,4-dioxane and underwent a thermal-induced phase separation (TIPS) followed by lyophilization. The TIPS process lead to a nanoporous structure shielded by the printed microstructure (NSP-PCL). Sixteen Landrace pigs were divided...... into two groups with 8 and 12 weeks follow-up, respectively. A total of six nonpenetrating holes were drilled in the calvaria of each animal. The size of the cylindrical defects was h 10 mm and Ø 10 mm. The defects were distributed randomly using following groups: (a) NSP-PCL scaffold, (b) FDM-PCL scaffold...

World alliance against antibiotic resistance: The WAAAR declaration against antibiotic resistance.

Science.gov (United States)

Carlet, Jean

2015-01-01

We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species. Preservation of the efficacy of antibiotics and to stabilization of antibiotic-susceptible bacterial ecosystems should be global goals. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

Science.gov (United States)

Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

2011-11-01

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

Injectable porous nano-hydroxyapatite/chitosan/tripolyphosphate scaffolds with improved compressive strength for bone regeneration

Energy Technology Data Exchange (ETDEWEB)

Uswatta, Suren P.; Okeke, Israel U. [Department of Bioengineering, The University of Toledo, Toledo, OH 43614 (United States); Jayasuriya, Ambalangodage C., E-mail: a.jayasuriya@utoledo.edu [Department of Bioengineering, The University of Toledo, Toledo, OH 43614 (United States); Department of Orthopaedic Surgery, The University of Toledo, Toledo, OH 43614 (United States)

2016-12-01

In this study we have fabricated porous injectable spherical scaffolds using chitosan biopolymer, sodium tripolyphosphate (TPP) and nano-hydroxyapatite (nHA). TPP was primarily used as an ionic crosslinker to crosslink nHA/chitosan droplets. We hypothesized that incorporating nHA into chitosan could support osteoconduction by emulating the mineralized cortical bone structure, and improve the Ultimate Compressive Strength (UCS) of the scaffolds. We prepared chitosan solutions with 0.5%, 1% and 2% (w/v) nHA concentration and used simple coacervation and lyophilization techniques to obtain spherical scaffolds. Lyophilized spherical scaffolds had a mean diameter of 1.33 mm (n = 25). Further, portion from each group lyophilized scaffolds were soaked and dried to obtain Lyophilized Soaked and Dried (LSD) scaffolds. LSD scaffolds had a mean diameter of 0.93 mm (n = 25) which is promising property for the injectability. Scanning Electron Microscopy images showed porous surface morphology and interconnected pore structures inside the scaffolds. Lyophilized and LSD scaffolds had surface pores < 10 and 2 μm, respectively. 2% nHA/chitosan LSD scaffolds exhibited UCS of 8.59 MPa compared to UCS of 2% nHA/chitosan lyophilized scaffolds at 3.93 MPa. Standardize UCS values were 79.98 MPa and 357 MPa for 2% nHA/chitosan lyophilized and LSD particles respectively. One-way ANOVA results showed a significant increase (p < 0.001) in UCS of 1% and 2% nHA/chitosan lyophilized scaffolds compared to 0% and 0.5% nHA/chitosan lyophilized scaffolds. Moreover, 2% nHA LSD scaffolds had significantly increased (p < 0.005) their mean UCS by 120% compared to 2% nHA lyophilized scaffolds. In a drawback, all scaffolds have lost their mechanical properties by 95% on the 2nd day when fully immersed in phosphate buffered saline. Additionally live and dead cell assay showed no cytotoxicity and excellent osteoblast attachment to both lyophilized and LSD scaffolds at the end of 14th day of in vitro

Injectable porous nano-hydroxyapatite/chitosan/tripolyphosphate scaffolds with improved compressive strength for bone regeneration

International Nuclear Information System (INIS)

Uswatta, Suren P.; Okeke, Israel U.; Jayasuriya, Ambalangodage C.

2016-01-01

In this study we have fabricated porous injectable spherical scaffolds using chitosan biopolymer, sodium tripolyphosphate (TPP) and nano-hydroxyapatite (nHA). TPP was primarily used as an ionic crosslinker to crosslink nHA/chitosan droplets. We hypothesized that incorporating nHA into chitosan could support osteoconduction by emulating the mineralized cortical bone structure, and improve the Ultimate Compressive Strength (UCS) of the scaffolds. We prepared chitosan solutions with 0.5%, 1% and 2% (w/v) nHA concentration and used simple coacervation and lyophilization techniques to obtain spherical scaffolds. Lyophilized spherical scaffolds had a mean diameter of 1.33 mm (n = 25). Further, portion from each group lyophilized scaffolds were soaked and dried to obtain Lyophilized Soaked and Dried (LSD) scaffolds. LSD scaffolds had a mean diameter of 0.93 mm (n = 25) which is promising property for the injectability. Scanning Electron Microscopy images showed porous surface morphology and interconnected pore structures inside the scaffolds. Lyophilized and LSD scaffolds had surface pores < 10 and 2 μm, respectively. 2% nHA/chitosan LSD scaffolds exhibited UCS of 8.59 MPa compared to UCS of 2% nHA/chitosan lyophilized scaffolds at 3.93 MPa. Standardize UCS values were 79.98 MPa and 357 MPa for 2% nHA/chitosan lyophilized and LSD particles respectively. One-way ANOVA results showed a significant increase (p < 0.001) in UCS of 1% and 2% nHA/chitosan lyophilized scaffolds compared to 0% and 0.5% nHA/chitosan lyophilized scaffolds. Moreover, 2% nHA LSD scaffolds had significantly increased (p < 0.005) their mean UCS by 120% compared to 2% nHA lyophilized scaffolds. In a drawback, all scaffolds have lost their mechanical properties by 95% on the 2nd day when fully immersed in phosphate buffered saline. Additionally live and dead cell assay showed no cytotoxicity and excellent osteoblast attachment to both lyophilized and LSD scaffolds at the end of 14th day of in vitro

Polycaprolactone Scaffolds Fabricated via Bioextrusion for Tissue Engineering Applications

Directory of Open Access Journals (Sweden)

Marco Domingos

2009-01-01

Full Text Available The most promising approach in Tissue Engineering involves the seeding of porous, biocompatible/biodegradable scaffolds, with donor cells to promote tissue regeneration. Additive biomanufacturing processes are increasingly recognized as ideal techniques to produce 3D structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. This paper presents a novel extrusion-based system to produce 3D scaffolds with controlled internal/external geometry for TE applications.The BioExtruder is a low-cost system that uses a proper fabrication code based on the ISO programming language enabling the fabrication of multimaterial scaffolds. Poly(ε-caprolactone was the material chosen to produce porous scaffolds, made by layers of directionally aligned microfilaments. Chemical, morphological, and in vitro biological evaluation performed on the polymeric constructs revealed a high potential of the BioExtruder to produce 3D scaffolds with regular and reproducible macropore architecture, without inducing relevant chemical and biocompatibility alterations of the material.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

Science.gov (United States)

Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

2010-08-24

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

Collagen-grafted porous HDPE/PEAA scaffolds for bone reconstruction.

Science.gov (United States)

Kim, Chang-Shik; Jung, Kyung-Hye; Kim, Hun; Kim, Chan-Bong; Kang, Inn-Kyu

2016-01-01

After tumor resection, bone reconstruction such as skull base reconstruction using interconnected porous structure is absolutely necessary. In this study, porous scaffolds for bone reconstruction were prepared using heat-pressing and salt-leaching methods. High-density polyethylene (HDPE) and poly(ethylene-co-acrylic acid) (PEAA) were chosen as the polymer composites for producing a porous scaffold of high mechanical strength and having high reactivity with biomaterials such as collagen, respectively. The porous structure was observed through surface images, and its intrusion volume and porosity were measured. Owing to the carboxylic acids on PEAA, collagen was successfully grafted onto the porous HDPE/PEAA scaffold, which was confirmed by FT-IR spectroscopy and electron spectroscopy for chemical analysis. Osteoblasts were cultured on the collagen-grafted porous scaffold, and their adhesion, proliferation, and differentiation were investigated. The high viability and growth of the osteoblasts suggest that the collagen-grafted porous HDPE/PEAA is a promising scaffold material for bone generation.

Poly(hydroxybutyrate)/cellulose acetate blend nanofiber scaffolds: Preparation, characterization and cytocompatibility

Energy Technology Data Exchange (ETDEWEB)

Zhijiang, Cai, E-mail: caizhijiang@hotmail.com [School of Textiles, Tianjin Polytechnic University, Tianjin 300387 (China); State Key Laboratory of Hollow Fiber Membrane Material and Processes, No 399 BingShuiXi Street, XiQing District, Tianjin, China, 300387 (China); Yi, Xu; Haizheng, Yang; Jia, Jianru; Liu, Yuanpei [School of Textiles, Tianjin Polytechnic University, Tianjin 300387 (China)

2016-01-01

Poly(hydroxybutyrate) (PHB)/cellulose acetate (CA) blend nanofiber scaffolds were fabricated by electrospinning using the blends of chloroform and DMF as solvent. The blend nanofiber scaffolds were characterized by SEM, FTIR, XRD, DSC, contact angle and tensile test. The blend nanofibers exhibited cylindrical, uniform, bead-free and random orientation with the diameter ranged from 80–680 nm. The scaffolds had very well interconnected porous fibrous network structure and large aspect surface areas. It was found that the presence of CA affected the crystallization of PHB due to formation of intermolecular hydrogen bonds, which restricted the preferential orientation of PHB molecules. The DSC result showed that the PHB and CA were miscible in the blend nanofiber. An increase in the glass transition temperature was observed with increasing CA content. Additionally, the mechanical properties of blend nanofiber scaffolds were largely influenced by the weight ratio of PHB/CA. The tensile strength, yield strength and elongation at break of the blend nanofiber scaffolds increased from 3.3 ± 0.35 MPa, 2.8 ± 0.26 MPa, and 8 ± 0.77% to 5.05 ± 0.52 MPa, 4.6 ± 0.82 MPa, and 17.6 ± 1.24% by increasing PHB content from 60% to 90%, respectively. The water contact angle of blend nanofiber scaffolds decreased about 50% from 112 ± 2.1° to 60 ± 0.75°. The biodegradability was evaluated by in vitro degradation test and the results revealed that the blend nanofiber scaffolds showed much higher degradation rates than the neat PHB. The cytocompatibility of the blend nanofiber scaffolds was preliminarily evaluated by cell adhesion studies. The cells incubated with PHB/CA blend nanofiber scaffold for 48 h were capable of forming cell adhesion and proliferation. It showed much better biocompatibility than pure PHB film. Thus, the prepared PHB/CA blend nanofiber scaffolds are bioactive and may be more suitable for cell proliferation suggesting that these scaffolds can be used for

Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue engineering

International Nuclear Information System (INIS)

Mota, Carlos; Danti, Serena; D’Alessandro, Delfo; Trombi, Luisa; Ricci, Claudio; Berrettini, Stefano; Puppi, Dario; Dinucci, Dinuccio; Chiellini, Federica; Milazzo, Mario; Stefanini, Cesare; Moroni, Lorenzo

2015-01-01

The tympanic membrane (TM) is a thin tissue able to efficiently collect and transmit sound vibrations across the middle ear thanks to the particular orientation of its collagen fibers, radiate on one side and circular on the opposite side. Through the combination of advanced scaffolds and autologous cells, tissue engineering (TE) could offer valuable alternatives to autografting in major TM lesions. In this study, a multiscale approach based on electrospinning (ES) and additive manufacturing (AM) was investigated to fabricate scaffolds, based on FDA approved copolymers, resembling the anatomic features and collagen fiber arrangement of the human TM. A single scale TM scaffold was manufactured using a custom-made collector designed to confer a radial macro-arrangement to poly(lactic-co-glycolic acid) electrospun fibers during their deposition. Dual and triple scale scaffolds were fabricated combining conventional ES with AM to produce poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer scaffolds with anatomic-like architecture. The processing parameters were optimized for each manufacturing method and copolymer. TM scaffolds were cultured in vitro with human mesenchymal stromal cells, which were viable, metabolically active and organized following the anisotropic character of the scaffolds. The highest viability, cell density and protein content were detected in dual and triple scale scaffolds. Our findings showed that these biomimetic micro-patterned substrates enabled cell disposal along architectural directions, thus appearing as promising substrates for developing functional TM replacements via TE. (paper)

Development of Chitosan Scaffolds with Enhanced Mechanical Properties for Intestinal Tissue Engineering Applications.

Science.gov (United States)

Zakhem, Elie; Bitar, Khalil N

2015-10-13

Massive resections of segments of the gastrointestinal (GI) tract lead to intestinal discontinuity. Functional tubular replacements are needed. Different scaffolds were designed for intestinal tissue engineering application. However, none of the studies have evaluated the mechanical properties of the scaffolds. We have previously shown the biocompatibility of chitosan as a natural material in intestinal tissue engineering. Our scaffolds demonstrated weak mechanical properties. In this study, we enhanced the mechanical strength of the scaffolds with the use of chitosan fibers. Chitosan fibers were circumferentially-aligned around the tubular chitosan scaffolds either from the luminal side or from the outer side or both. Tensile strength, tensile strain, and Young's modulus were significantly increased in the scaffolds with fibers when compared with scaffolds without fibers. Burst pressure was also increased. The biocompatibility of the scaffolds was maintained as demonstrated by the adhesion of smooth muscle cells around the different kinds of scaffolds. The chitosan scaffolds with fibers provided a better candidate for intestinal tissue engineering. The novelty of this study was in the design of the fibers in a specific alignment and their incorporation within the scaffolds.

Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

Science.gov (United States)

Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

2016-03-01

Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

Membrane-reinforced three-dimensional electrospun silk fibroin scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Yang, Sung Yeun; Hwang, Tae Heon; Ryu, WonHyoung; Che, Lihua; Oh, Jin Soo; Ha, Yoon

2015-01-01

Electrospun silk fibroin (SF) scaffolds have drawn much attention because of their resemblance to natural tissue architecture such as extracellular matrix, and the biocompatibility of SF as a candidate material to replace collagen. However, electrospun scaffolds lack the physical integrity of bone tissue scaffolds, which require resistance to mechanical loadings. In this work, we propose membrane-reinforced electrospun SF scaffolds by a serial process of electrospinning and freeze-drying of SF solutions in two different solvents: formic acid and water, respectively. After wet electrospinning followed by replacement of methanol with water, SF nanofibers dispersed in water were mixed with aqueous SF solution. Freeze-drying of the mixed solution resulted in 3D membrane-connected SF nanofibrous scaffolds (SF scaffolds) with a thickness of a few centimeters. We demonstrated that the SF concentration of aqueous SF solution controlled the degree of membrane reinforcement between nanofibers. It was also shown that both increase in degree of membrane reinforcement and inclusion of hydroxyapatite (HAP) nanoparticles resulted in higher resistance to compressive loadings of the SF scaffolds. Culture of human osteoblasts on collagen, SF, and SF-HAP scaffolds showed that both SF and SF-HAP scaffolds had biocompatibility and cell proliferation superior to that of the collagen scaffolds. SF-HAP scaffolds with and without BMP-2 were used for in vivo studies for 4 and 8 weeks, and they showed enhanced bone tissue formation in rat calvarial defect models. (paper)

Biodegradation and bioresorption of poly(-caprolactone) nanocomposite scaffolds

CSIR Research Space (South Africa)

Mkhabela, V

2015-08-01

Full Text Available confirmed the elemental composition of the scaffolds. The phase composition of the scaffolds was shown by XRD, which also indicated a decrease in crystallinity with the introduction of nanoclay. Biodegradability studies which were conducted in simulated...

Acellular organ scaffolds for tumor tissue engineering

Science.gov (United States)

Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

2015-12-01

Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

Science.gov (United States)

Lan, Sheeny K.

Bone grafts are utilized clinically to guide tissue regeneration. Autologous bone and allogeneic bone are the current clinical standards. However, there are significant limitations to their use. To address the need for alternatives to autograft and allograft, researchers have worked to develop synthetic grafts, also referred to as scaffolds. Despite extensive efforts in this area, a gap persists between basic research and clinical application. In particular, solutions for repairing critical size and/or load-bearing defects are lacking. The aim of this thesis work was to address two critical barriers preventing design of successful tissue engineering constructs for bone regeneration within critical size and/or load-bearing defects. Those barriers are insufficient osteointegration and slow neovascularization. In this work, the effects of scaffold microporosity, recombinant human bone morphogenetic protein-2 delivery and endothelial colony forming cell vasculogenesis were evaluated in the context of bone formation in vivo. This was accomplished to better understand the role of these factors in bone regeneration, which may translate to improvements in tissue engineering construct design. Biphasic calcium phosphate (BCP) scaffolds with controlled macro- and microporosity were implanted in porcine mandibular defects. Evaluation of the BCP scaffolds after in vivo implantation showed, for the first time, osteocytes embedded in bone within scaffold micropores (macro and micro length scales, leaving no "dead space" or discontinuities of bone in the defect site. The scaffold forms a living composite upon integration with regenerating bone and this has significant implications with regard to improved scaffold mechanical properties. The presence of osteocytes within scaffold micropores is an indication of scaffold osteoinductivity because a chemotactic factor must be present to induce cell migration into pores on the order of the cell diameter. It is likely that the scaffold

Systemic antibiotics in periodontics.

Science.gov (United States)

Slots, Jørgen

2004-11-01

This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession.

Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

Science.gov (United States)

Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

2016-06-01

Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture.

Overlapping bio-absorbable scaffolds: Aim for D2D technique?

Science.gov (United States)

Khan, Asaad A; Dangas, George D

2018-06-01

The results of overlapping metallic stents have been concerning but this practice is often unavoidable in the setting of long or tortuous lesions, diameter discrepancy of proximal and distal vessel, and for residual dissections. Theoretically, bio-absorbable scaffolds may carry an advantage over metallic stents due to the progressive resorption of the scaffold theoretically rendering the overlap a non-issue; this has not been clinically evident. Since stent/scaffold overlap cannot be entirely avoided, improved stent delivery/deployment and scaffold design modification may reduce complications in this complex patient subset. © 2018 Wiley Periodicals, Inc.

Biochemical properties of Hemigraphis alternata incorporated chitosan hydrogel scaffold.

Science.gov (United States)

Annapoorna, M; Sudheesh Kumar, P T; Lakshman, Lakshmi R; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V; Jayakumar, R

2013-02-15

In this work, Hemigraphis alternata extract incorporated chitosan scaffold was synthesized and characterized for wound healing. The antibacterial activity of Hemigraphis incorporated chitosan scaffold (HIC) against Escherichia coli and Staphylococcus aureus was evaluated which showed a reduction in total colony forming units by 45-folds toward E. coli and 25-fold against S. aureus respectively. Cell viability studies using Human Dermal Fibroblast cells (HDF) showed 90% viability even at 48 h when compared to the chitosan control. The herbal scaffold made from chitosan was highly haemostatic and antibacterial. The obtained results were in support that the herbal scaffold can be effectively applied for infectious wounds. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sol-gel synthesis of bioactive glass porous scaffolds with addition of porogen agent; Sintese sol-gel de scaffolds porosos de vidro bioativo com adicao de agente porogenico

Energy Technology Data Exchange (ETDEWEB)

Guimaraes, F.B.A.P.; Barrioni, B.R.; Oliveira, A.C.X.; Oliveira, A.A.R.; Pereira, M.M., E-mail: fabianabapg@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Escola de Engenharia. Dept. Engenharia Metalurgica e de Materiais

2016-10-15

The use of biomaterials capable of generating a biological response has been one of the biggest progresses in regenerative medicine, due to their ability to support growth stimulation and damaged tissue regeneration. In this context, bioceramics, particularly bioactive glass (BG), were the subject of many studies. The technique of porogen agent addition for the synthesis of scaffolds is an interesting procedure, because several types of porogen agents can be used. The aim of the present work was to obtain scaffolds using four porogen agents and to evaluate the effects that a change in treatment temperature can have on their crystallinity. Scaffolds of sol-gel bioactive glass 100S (100% SiO{sub 2}) using as porogen agents paraffin 1, paraffin 2, wax and CMC (carboxymethyl cellulose) were synthesized and characterized. As the best results were obtained with paraffin 1, scaffolds 58S (60%SiO{sub 2} -36%CaO-4%P{sub 2}O{sub 5} ) and 100S using paraffin 1 as porogen agent were prepared. The scaffolds were submitted to different treatment temperatures to evaluate the effect on their crystallinity. Pore structure was analyzed by scanning electron microscopy and micro-computed tomography. Scaffolds presented satisfactory pore size and pore size distribution, important characteristics for scaffolds because they allow cell migration, nutrient transport, vascularisation and tissue ingrowth. X-ray powder diffraction showed the amorphous nature of the scaffolds. At 900 °C, scaffolds BG 58S and 100S showed a small increase in crystallinity. BET analysis (N{sub 2} -adsorption) indicated a mesoporous structure. The specific surface area varied from 73.2 m{sup 2} /g for scaffold 58S treated at 800 °C to 331.2 m{sup 2} /g for scaffold 100S treated at 800 °C. The materials obtained showed no toxic effects by MTT cytotoxicity assays. Results showed that the development of scaffolds is possible using porogen agents, with 3D interconnected porous structure and might therefore be a

Enzymatically biomineralized chitosan scaffolds for tissue-engineering applications.

NARCIS (Netherlands)

Dash, M.; Samal, S.K.; Douglas, T.E.L.; Schaubroeck, D.; Leeuwenburgh, S.C.G.; Voort, P. van der; Declercq, H.A.; Dubruel, P.

2017-01-01

Porous biodegradable scaffolds represent promising candidates for tissue-engineering applications because of their capability to be preseeded with cells. We report an uncrosslinked chitosan scaffold designed with the aim of inducing and supporting enzyme-mediated formation of apatite minerals in the

Electrospinning thermoplastic polyurethane/graphene oxide scaffolds for small diameter vascular graft applications

Energy Technology Data Exchange (ETDEWEB)

Jing, Xin [National Engineering Research Center of Novel Equipment for Polymer Processing, The Key Laboratory of Polymer Processing Engineering of Ministry of Education, South China University of Technology, Guangzhou (China); Department of Mechanical Engineering, University of Wisconsin–Madison, WI (United States); Wisconsin Institute for Discovery, University of Wisconsin–Madison, WI (United States); Mi, Hao-Yang [National Engineering Research Center of Novel Equipment for Polymer Processing, The Key Laboratory of Polymer Processing Engineering of Ministry of Education, South China University of Technology, Guangzhou (China); Salick, Max R. [Wisconsin Institute for Discovery, University of Wisconsin–Madison, WI (United States); Department of Engineering Physics, University of Wisconsin–Madison, WI (United States); Cordie, Travis M. [Wisconsin Institute for Discovery, University of Wisconsin–Madison, WI (United States); Department of Biomedical Engineering, University of Wisconsin–Madison, WI (United States); Peng, Xiang-Fang, E-mail: pmxfpeng@scut.edu.cn [National Engineering Research Center of Novel Equipment for Polymer Processing, The Key Laboratory of Polymer Processing Engineering of Ministry of Education, South China University of Technology, Guangzhou (China); Turng, Lih-Sheng, E-mail: turng@engr.wisc.edu [Department of Mechanical Engineering, University of Wisconsin–Madison, WI (United States); Wisconsin Institute for Discovery, University of Wisconsin–Madison, WI (United States)

2015-04-01

Fabrication of small diameter vascular grafts plays an important role in vascular tissue engineering. In this study, thermoplastic polyurethane (TPU)/graphene oxide (GO) scaffolds were fabricated via electrospinning at different GO contents as potential candidates for small diameter vascular grafts. In terms of mechanical and surface properties, the tensile strength, Young's modulus, and hydrophilicity of the scaffolds increased with an increase of GO content while plasma treatment dramatically improved the scaffold hydrophilicity. Mouse fibroblast (3T3) and human umbilical vein endothelial cells (HUVECs) were cultured on the scaffolds separately to study their biocompatibility and potential to be used as vascular grafts. It was found that cell viability for both types of cells, fibroblast proliferation, and HUVEC attachment were the highest at a 0.5 wt.% GO loading whereas oxygen plasma treatment also enhanced HUVEC viability and attachment significantly. In addition, the suture retention strength and burst pressure of tubular TPU/GO scaffolds containing 0.5 wt.% GO were found to meet the requirements of human blood vessels, and endothelial cells were able to attach to the inner surface of the tubular scaffolds. Platelet adhesion tests using mice blood indicated that vascular scaffolds containing 0.5% GO had low platelet adhesion and activation. Therefore, the electrospun TPU/GO tubular scaffolds have the potential to be used in vascular tissue engineering. - Highlights: • TPU/GO vascular scaffolds were prepared via electrospinning. • The addition of GO improved the modulus and hydrophilicity of the scaffolds. • Fibroblast cell culture verified the scaffolds' biocompatibility. • Endothelial cell culture verified the scaffolds' vascular graft affinity. • The mechanical properties fulfilled the requirements of vascular grafts.

Forgotten antibiotics

DEFF Research Database (Denmark)

Pulcini, Céline; Bush, Karen; Craig, William A

2012-01-01

In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious...

Optimizing Antibiotic Use in Nursing Homes Through Antibiotic Stewardship.

Science.gov (United States)

Sloane, Philip D; Huslage, Kirk; Kistler, Christine E; Zimmerman, Sheryl

2016-01-01

Antibiotic stewardship is becoming a requirement for nursing homes. Programs should be interdisciplinary and multifaceted; should have support from nursing home administrators; and should aim to promote antibiotics only when needed, not just in case. Recommended components include use of evidence-based guidelines; ongoing monitoring of antibiotic prescriptions, cultures, and study results; monitoring of health outcomes; use of nursing home-specific antibiograms; regular reporting and feedback to medical providers and nurses; and education of residents and families. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

Directed Self-Inquiry: A Scaffold for Teaching Laboratory Report Writing

Science.gov (United States)

Deiner, L. Jay; Newsome, Daniel; Samaroo, Diana

2012-01-01

A scaffold was created for the explicit instruction of laboratory report writing. The scaffold breaks the laboratory report into sections and teaches students to ask and answer questions in order to generate section-appropriate content and language. Implementation of the scaffold is done through a series of section-specific worksheets that are…

Chitosan/bioactive glass nanoparticles scaffolds with shape memory properties.

Science.gov (United States)

Correia, Cristina O; Leite, Álvaro J; Mano, João F

2015-06-05

We propose a combination of chitosan (CHT) with bioactive glass nanoparticles (BG-NPs) in order to produce CHT/BG-NPs scaffolds that combine the shape memory properties of chitosan and the biomineralization ability of BG-NPs for applications in bone regeneration. The addition of BG-NPs prepared by a sol-gel route to the CHT polymeric matrix improved the bioactivity of the nanocomposite scaffold, as seen by the precipitation of bone-like apatite layer upon immersion in simulated body fluid (SBF). Shape memory tests were carried out while the samples were immersed in varying compositions of water/ethanol mixtures. Dehydration with ethanol enables to fix a temporary shape of a deformed scaffold that recovers the initial geometry upon water uptake. The scaffolds present good shape memory properties characterized by a recovery ratio of 87.5% for CHT and 89.9% for CHT/BG-NPs and a fixity ratio of 97.2% for CHT and 98.2% for CHT/BG-NPs (for 30% compressive deformation). The applicability of such structures was demonstrated by a good geometrical accommodation of a previously compressed scaffold in a bone defect. The results indicate that the developed CHT/BG-NPs nanocomposite scaffolds have potential for being applied in bone tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pervasive antibiotic misuse in the Cambodian community: antibiotic-seeking behaviour with unrestricted access

Directory of Open Access Journals (Sweden)

Chhorvoin Om

2017-03-01

Full Text Available Abstract Background Antibiotic misuse is widespread in resource-limited countries such as Cambodia where the burden of infectious diseases is high and access to antibiotics is unrestricted. We explored healthcare seeking behaviour related to obtaining antibiotics and drivers of antibiotic misuse in the Cambodian community. Methods In-depth interviews were held with family members of patients being admitted in hospitals and private pharmacies termed pharmacy attendants in the catchment areas of the hospitals. Nurses who run community primary healthcare centres located within the hospital catchment areas were invited to attend focus group discussions. Nvivo version 10 was used to code and manage thematic data analysis. Results We conducted individual interviews with 35 family members, 7 untrained pharmacy attendants and 3 trained pharmacists and 6 focus group discussions with 30 nurses. Self-medication with a drug-cocktail was widespread and included broad-spectrum antibiotics for mild illness. Unrestricted access to antibiotics was facilitated by various community enablers including pharmacies or drug outlets, nurse suppliers and unofficial village medical providers referred to as “village Pett” whose healthcare training has historically been in the field and not at university. These enablers supplied the community with various types of antibiotics including broad spectrum fluoroquinolones and cephalosporins. When treatment was perceived to be ineffective patients would prescriber-shop various suppliers who would unfailingly provide them with antibiotics. The main driver of the community’s demand for antibiotics was a mistaken belief in the benefits of antibiotics for a common cold, high temperature, pain, malaria and ‘Roleak’ which includes a broad catch-all for perceived inflammatory conditions. For severe illnesses, patients would attend a community healthcare centre, hospital, or when their finances permitted, a private prescriber

Controlled release of antibiotics encapsulated in the electrospinning polylactide nanofibrous scaffold and their antibacterial and biocompatible properties

International Nuclear Information System (INIS)

Wang, Shu-Dong; Zhang, Sheng-Zhong; Liu, Hua; Zhang, You-Zhu

2014-01-01

In this research, the drug loaded polylactide nanofibers are fabricated by electrospinning. Morphology, microstructure and mechanical properties are characterized. Properties and mechanism of the controlled release of the nanofibers are investigated. The results show that the drug loaded polylactide nanofibers do not show dispersed phase, and there is a good compatibility between polylactide and drugs. FTIR spectra show that drugs are encapsulated inside the polylactide nanofibers, and drugs do not break the structure of polylcatide. Flexibility of drug loaded polylactide scaffolds is higher than that of the pure polylactide nanofibers. Release rate of the drug loaded nanofibers is significantly slower than that of the drug powder. Release rate increases with the increase of the drugs’ concentration. The research mechanism suggests a typical diffusion-controlled release of the three loaded drugs. Antibacterial and cell culture show that drug loaded nanofibers possess effective antibacterial activity and biocompatible properties. (papers)

Preparation and biocompatibility evaluation of apatite/wollastonite-derived porous bioactive glass ceramic scaffolds

International Nuclear Information System (INIS)

Zhang Hua; Ye Xiaojian; Li Jiashun

2009-01-01

An apatite/wollastonite-derived (A/W) porous glass ceramic scaffold with highly interconnected pores was successfully fabricated by adding a plastic porosifier. The morphology, porosity and mechanical strength were characterized. The results showed that the glass ceramic scaffold with controllable pore size and porosity displayed open macropores. In addition, good in vitro bioactivity was found for the scaffold obtained by soaking it in simulated body fluid. Mesenchymal stem cells (MSCs) were cultured, expanded and seeded on the scaffold, and the adhesion and proliferation of MSCs were determined using MTT assay and environmental scanning electron microscopy (ESEM). The results revealed that the scaffold was biocompatible and had no negative effects on the MSCs in vitro. The in vivo biocompatibility and osteogenicity were investigated by implanting both the pure scaffold and the MSC/scaffold construct in rabbit mandibles and studying histologically. The results showed that the glass ceramic scaffold exhibited good biocompatibility and osteoconductivity. Moreover, the introduction of MSCs into the scaffold observably improved the efficiency of new bone formation, especially at the initial stage after implantation. However, the glass ceramic scaffold showed the same good biocompatibility and osteogenicity as the hybrid one at the later stage. These results indicate that porous bioactive scaffolds based on the original apatite-wollastonite glass ceramic fulfil the basic requirements of a bone tissue engineering scaffold.

[Antibiotics: present and future].

Science.gov (United States)

Bérdy, János

2013-04-14

The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

Antibiotic resistance - the interplay between antibiotic use in animals and human beings

DEFF Research Database (Denmark)

Singer, R.S.; Finch, R.; Wegener, Henrik Caspar

2003-01-01

Antibiotic-resistant bacteria were first identified in the 1940s, but while new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. Today, the excessive use of antibiotics compounded by the paucity of new agents on the market has...... meant the problem of antibiotic resistance is fast escalating into a global health crisis. There is no doubt that misuse of these drugs in human beings has contributed to the increasing rates of resistance, but recently the use of antibiotics in food animals and its consequent effect on resistance....... There is a growing concern over the transmission of resistant bacteria via the food chain. Many questions will be difficult to resolve, such as how do you distinguish the fraction of resistance in human beings that originated from animals? If we wait to see evidence that a significant amount of antibiotic resistance...

Bio-inspired citrate functionalized apatite coating on rapid prototyped titanium scaffold

Energy Technology Data Exchange (ETDEWEB)

Yu, Peng [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Lu, Fang [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006 (China); Zhu, Wenjun [Department of Prosthodontics, Guanghua School of Stomatology, Guang Dong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Wang, Di [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Zhu, Xiaojing [Department of Prosthodontics, Guanghua School of Stomatology, Guang Dong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Tan, Guoxin, E-mail: tanguoxin@126.com [Institute of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006 (China); Wang, Xiaolan [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Zhang, Yu; Li, Lihua [General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010 (China); Ning, Chengyun, E-mail: imcyning@scut.edu.cn [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China)

2014-09-15

Highlights: • Designed and reproducible porous titanium scaffolds were produced. • Hydrophilic nanoporous film was built on scaffold. • Apatite coating was deposited on scaffold under the modulation of citrate ions. • Citrate ions could affect CO{sub 3}{sup 2−} incorporation in apatite coatings. - Abstract: Scaffold functionalized with appropriate osteogenic coatings can significantly improve implant-bone response. In this study, with designed model and optimized manufacture parameters, reproducible and precise titanium scaffolds were produced. Reconstructed three-dimensional image and sectional structure of the scaffold were examined by micro-computed tomography and relative software. Alkali treatment was carried out on these manufactured porous scaffolds to produce nanoporous hydrophilic film. After 6 days deposition in simulated body fluid (SBF) containing sodium citrate (SC-SBF), plate-like amorphous calcium phosphate (ACP) coating was deposited on scaffold surface. Ultrasonication tests qualitatively indicated an enhanced adhesion force of apatite coatings deposited in SC-SBF compared to that deposited in SBF. And the effect of citrate ions on the CO{sub 3}{sup 2−} incorporation rate in apatite coating was quantitatively examined by bending vibration of CO{sub 3}{sup 2−} at ∼874 cm{sup −1}. Results indicated the highest carbonate content was obtained at the citrate ion concentration of 6 × 10{sup −5} mol/L in SC-SBF. These three-dimensional porous titanium-apatite hybrid scaffolds are expected to find application in bone tissue regeneration.

Microstructures and martensitic transformation behavior of superelastic Ti-Ni-Ag scaffolds

Energy Technology Data Exchange (ETDEWEB)

Li, Shuanglei; Kim, Eun-soo [School of Materials Science and Engineering & ERI, Gyeongsang National University, 900 Gazwadong, Jinju, Gyeongnam 660-701 (Korea, Republic of); Kim, Yeon-wook [Department of Material Engineering, Keimyung University, 1000 Shindang-dong, Dalseo-gu, Daegu 704-701 (Korea, Republic of); Nam, Tae-hyun, E-mail: tahynam@gnu.ac.kr [School of Materials Science and Engineering & ERI, Gyeongsang National University, 900 Gazwadong, Jinju, Gyeongnam 660-701 (Korea, Republic of)

2016-10-15

Highlights: • The B2-R-B19′ transformation occurred in 49Ti-50.3Ni-0.7Ag alloy fibers. • Annealing treated alloy fibers showed superelastic recovery ratio of 93%. • Ageing treated scaffold had an elastic modulus of 0.67 GPa. • Ageing treated scaffold exhibited good superelasticity at human body temperature. - Abstract: Ti-Ni-Ag scaffolds were prepared by sintering rapidly solidified alloy fibers. Microstructures and transformation behaviors of alloy fibers and scaffolds were investigated by means of electron probe micro-analyzer (EPMA), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The B2-R-B19′ transformation occurs in alloy fibers. The alloy fibers have good superelasticity with superelastic recovery ratio of 93% after annealing heat treatment. The as-sintered Ti-Ni-Ag scaffolds possess three-dimensional and interconnected pores and have the porosity level of 80%. The heat treated Ti-Ni-Ag scaffolds not only have an elastic modulus of 0.67 GPa, which match well with that of cancellous bone, but also show excellent superelasticity at human body temperature. In terms of the mechanical properties, the Ti-Ni-Ag scaffolds in this study can meet the main requirements of bone scaffold for the purpose of bone replacement applications.

A Ternary Nanofibrous Scaffold Potential for Central Nerve System Tissue Engineering.

Science.gov (United States)

Saadatkish, Niloufar; Nouri Khorasani, Saied; Morshed, Mohammad; Allafchian, Ali-Reza; Beigi, Mohammad-Hossein; Masoudi Rad, Maryam; Nasr-Esfahani, Mohammad Hossein; Esmaeely Neisiany, Rasoul

2018-04-10

In the present research, a ternary Polycaprolactone (PCL)/gelatin/fibrinogen nanofibrous scaffold for tissue engineering application was developed. Through this combination, PCL improved the scaffold mechanical properties; meanwhile, gelatin and fibrinogen provided more hydrophilicity and cell proliferation. Three types of nanofibrous scaffolds containing different fibrinogen contents were prepared and characterized. Morphological study of the nanofibers showed that the prepared nanofibers were smooth, uniform without any formation of beads with a significant reduction in nanofiber diameter after incorporation of fibrinogen. The chemical characterization of the scaffolds confirmed that no chemical reaction occurred between the scaffold components. The tensile test results of the scaffolds showed that increasing in fibrinogen content led to a decrease in mechanical properties. Furthermore, Adipose-derived stem cells (ADSCs) were employed to evaluate cell-scaffold interaction. Cell culture results indicated that higher cell proliferation occurred for the higher amount of fibrinogen. Statistical analysis was also carried out to evaluate the significant difference for the obtained results of water droplet contact angle and cell culture. Therefore, the results confirmed that PCL/Gel/Fibrinogen scaffold has a good potential for tissue engineering applications including Central Nerve System (CNS) tissue engineering. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Noninvasive Evaluation of Injectable Chitosan/Nano-Hydroxyapatite/Collagen Scaffold via Ultrasound

Directory of Open Access Journals (Sweden)

Yan Chen

2012-01-01

Full Text Available To meet the challenges of designing an in situ forming scaffold and regenerating bone with complex three-dimensional (3D structures, an in situ forming hydrogel scaffold based on nano-hydroxyapatite (nHA, collagen (Col, and chitosan (CS was synthesized. Currently, only a limited number of techniques are available to mediate and visualize the injection process of the injectable biomaterials directly and noninvasively. In this study, the potential of ultrasound for the quantitative in vivo evaluation of tissue development in CS/nHAC scaffold was evaluated. The CS/nHAC scaffold was injected into rat subcutaneous tissue and evaluated for 28 days. Quantitative measurements of the gray-scale value, volume, and blood flow of the scaffold were evaluated using diagnostic technique. This study demonstrates that ultrasound can be used to noninvasively and nondestructively monitor and evaluate the in vivo characteristics of injectable bone scaffold. In comparison to the CS, the CS/nHAC scaffold showed a greater stiffness, less degradation rate, and better blood supply in the in vivo evaluation. In conclusion, the diagnostic ultrasound method is a good tool to evaluate the in vivo formation of injectable bone scaffolds and facilitates the broad use to monitor tissue development and remodeling in bone tissue engineering.

Improving Students' Speaking Ability through Scaffolding Technique

Directory of Open Access Journals (Sweden)

Gede Ginaya

2018-03-01

Full Text Available Students often got confused and felt hesitant when they speak English. This situation had caused poor speaking ability, which then lead to serious problem in the teaching-learning process.  The application of scaffolding technique in the EFL learning might be the ideal solution; it had some principles that could improve the students’ speaking ability. This research is aimed at finding out the effect of the implementing Scaffolding Technique towards the students’ speaking ability. Participants were 50 (27 males and 23 females third-semester students, enrolled in a three-year diploma program in Travel and Tourism Business, State Polytechnic of Bali in 2017/2018 academic year. The students in the experimental group were given communicative activities such as brainstorming, business games, simulation, WebQuest, problem-solving, which were carefully designed to necessitate the implementation of the scaffolding technique. The students in the control group were taught by the deductive method of the lesson book. The students’ performance in the post-test was compared for both groups in order to determine whether there were significant differences between the groups in relation to the treatment. Significant differences occurring in the experimental group’s post-test speaking performance when compared to the pre-test indicate that the implementation of scaffolding technique can improve students’ speaking ability. The result of this study indicates scaffolding technique has the potential for use in promoting students’ speaking ability

Demographics of antibiotic persistence

DEFF Research Database (Denmark)

Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric Scaffolds for Neural Tissue Engineering and Neuronal Regeneration

KAUST Repository

Limongi, Tania; Rocchi, A.; Cesca, F.; Tan, H.; Miele, E.; Giugni, Andrea; Orlando, M.; Perrone Donnorso, M.; Perozziello, G.; Benfenati, Fabio; Di Fabrizio, Enzo M.

2018-01-01

Biopolymers are increasingly employed for neuroscience applications as scaffolds to drive and promote neural regrowth, thanks to their ability to mediate the upload and subsequent release of active molecules and drugs. Synthetic degradable polymers are characterized by different responses ranging from tunable distension or shrinkage to total dissolution, depending on the function they are designed for. In this paper we present a biocompatible microfabricated poly-ε-caprolactone (PCL) scaffold for primary neuron growth and maturation that has been optimized for the in vitro controlled release of brain-derived neurotrophic factor (BDNF). We demonstrate that the designed morphology confers to these devices an enhanced drug delivery capability with respect to monolithic unstructured supports. After incubation with BDNF, micropillared PCL devices progressively release the neurotrophin over 21 days in vitro. Moreover, the bioactivity of released BDNF is confirmed using primary neuronal cultures, where it mediates a consistent activation of BDNF signaling cascades, increased synaptic density, and neuronal survival. These results provide the proof-of-principle on the fabrication process of micropatterned PCL devices, which represent a promising therapeutic option to enhance neuronal regeneration after lesion and for neural tissue engineering and prosthetics.

Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric Scaffolds for Neural Tissue Engineering and Neuronal Regeneration

KAUST Repository

Limongi, Tania

2018-04-04

Biopolymers are increasingly employed for neuroscience applications as scaffolds to drive and promote neural regrowth, thanks to their ability to mediate the upload and subsequent release of active molecules and drugs. Synthetic degradable polymers are characterized by different responses ranging from tunable distension or shrinkage to total dissolution, depending on the function they are designed for. In this paper we present a biocompatible microfabricated poly-ε-caprolactone (PCL) scaffold for primary neuron growth and maturation that has been optimized for the in vitro controlled release of brain-derived neurotrophic factor (BDNF). We demonstrate that the designed morphology confers to these devices an enhanced drug delivery capability with respect to monolithic unstructured supports. After incubation with BDNF, micropillared PCL devices progressively release the neurotrophin over 21 days in vitro. Moreover, the bioactivity of released BDNF is confirmed using primary neuronal cultures, where it mediates a consistent activation of BDNF signaling cascades, increased synaptic density, and neuronal survival. These results provide the proof-of-principle on the fabrication process of micropatterned PCL devices, which represent a promising therapeutic option to enhance neuronal regeneration after lesion and for neural tissue engineering and prosthetics.

Implementation of an antibiotic checklist increased appropriate antibiotic use in the hospital on Aruba

NARCIS (Netherlands)

van Daalen, Frederike Vera; Lagerburg, Anouk; de Kort, Jaclyn; Sànchez Rivas, Elena; Geerlings, Suzanne Eugenie

2017-01-01

No interventions have yet been implemented to improve antibiotic use on Aruba. In the Netherlands, the introduction of an antibiotic checklist resulted in more appropriate antibiotic use in nine hospitals. The aim of this study was to introduce the antibiotic checklist on Aruba, test its

The effect of scaffold pore size in cartilage tissue engineering.

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Nava, Michele M; Draghi, Lorenza; Giordano, Carmen; Pietrabissa, Riccardo

2016-07-26

The effect of scaffold pore size and interconnectivity is undoubtedly a crucial factor for most tissue engineering applications. The aim of this study was to examine the effect of pore size and porosity on cartilage construct development in different scaffolds seeded with articular chondrocytes. We fabricated poly-L-lactide-co-trimethylene carbonate scaffolds with different pore sizes, using a solvent-casting/particulate-leaching technique. We seeded primary bovine articular chondrocytes on these scaffolds, cultured the constructs for 2 weeks and examined cell proliferation, viability and cell-specific production of cartilaginous extracellular matrix proteins, including GAG and collagen. Cell density significantly increased up to 50% with scaffold pore size and porosity, likely facilitated by cell spreading on the internal surface of bigger pores, and by increased mass transport of gases and nutrients to cells, and catabolite removal from cells, allowed by lower diffusion barriers in scaffolds with a higher porosity. However, both the cell metabolic activity and the synthesis of cartilaginous matrix proteins significantly decreased by up to 40% with pore size. We propose that the association of smaller pore diameters, causing 3-dimensional cell aggregation, to a lower oxygenation caused by a lower porosity, could have been the condition that increased the cell-specific synthesis of cartilaginous matrix proteins in the scaffold with the smallest pores and the lowest porosity among those tested. In the initial steps of in vitro cartilage engineering, the combination of small scaffold pores and low porosity is an effective strategy with regard to the promotion of chondrogenesis.

Microscale versus nanoscale scaffold architecture for mesenchymal stem cell chondrogenesis.

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Shanmugasundaram, Shobana; Chaudhry, Hans; Arinzeh, Treena Livingston

2011-03-01

Nanofiber scaffolds, produced by the electrospinning technique, have gained widespread attention in tissue engineering due to their morphological similarities to the native extracellular matrix. For cartilage repair, studies have examined their feasibility; however these studies have been limited, excluding the influence of other scaffold design features. This study evaluated the effect of scaffold design, specifically examining a range of nano to micron-sized fibers and resulting pore size and mechanical properties, on human mesenchymal stem cells (MSCs) derived from the adult bone marrow during chondrogenesis. MSC differentiation was examined on these scaffolds with an emphasis on temporal gene expression of chondrogenic markers and the pluripotent gene, Sox2, which has yet to be explored for MSCs during chondrogenesis and in combination with tissue engineering scaffolds. Chondrogenic markers of aggrecan, chondroadherin, sox9, and collagen type II were highest for cells on micron-sized fibers (5 and 9 μm) with pore sizes of 27 and 29 μm, respectively, in comparison to cells on nano-sized fibers (300 nm and 600 to 1400 nm) having pore sizes of 2 and 3 μm, respectively. Undifferentiated MSCs expressed high levels of the Sox2 gene but displayed negligible levels on all scaffolds with or without the presence of inductive factors, suggesting that the physical features of the scaffold play an important role in differentiation. Micron-sized fibers with large pore structures and mechanical properties comparable to the cartilage ECM enhanced chondrogenesis, demonstrating architectural features as well as mechanical properties of electrospun fibrous scaffolds enhance differentiation.

Impact of pharmacist intervention on antibiotic use and prophylactic antibiotic use in urology clean operations.

Science.gov (United States)

Zhou, Y; Ma, L-Y; Zhao, X; Tian, S-H; Sun, L-Y; Cui, Y-M

2015-08-01

The use of prophylactic antibiotics in clean operations was routine in China before 2011. Along with the appeal for using antibiotics rationally by WHO in 2011, China launched a national special rectification scheme on clinical use of antibiotics from April that year. The scheme, aimed at achieving rational use of antibiotics, made pharmacists part of the responsible medical team. Our objective was to describe the impacts of pharmacist intervention on the use of antibiotics, particularly in urology clean operations. Pharmacists participated in antibiotic stewardship programmes of the hospital and urological clinical work and conducted real-time interventions at the same time from 2011 to 2013. Data on the use of antibiotics between 2010 and 2013 in urology were collected. Comparison of the 2013 data with those of 2010 showed that antibiotic use density [AUD= DDDs*100/(The number of patients who were treated the same period*Average days in hospital). DDDs = Total drug consumption (g)/DDD. DDD is the Defined Daily Dose] decreased by 57·8(58·8%); average antibiotic cost decreased by 246·94 dollars; the cost of antibiotics as a percentage of total drug cost decreased by 27·7%; the rate of use of antibiotics decreased from 100% to 7·3%. The study illustrates how an antibiotic stewardship programme with pharmacist participation including real-time interventions can promote improved antibiotic-prescribing and significantly decrease costs. © 2015 John Wiley & Sons Ltd.

"Practical knowledge" and perceptions of antibiotics and antibiotic resistance among drugsellers in Tanzanian private drugstores

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Tomson Göran

2010-09-01

Full Text Available Abstract Background Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Methods Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Results Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85% said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic

Scaffolding Performance in EPSSs: Bridging Theory and Practice.

Science.gov (United States)

Hannafin, Michael J; McCarthy, James E.; Hannafin, Kathleen M.; Radtke, Paul

Electronic performance support systems (EPSS) help users accomplish tasks, using computational technologies. Scaffolding is the process through which efforts are supported while engaging a learning or performance task. A number of different types of scaffolds are possible, including conceptual, metacognitive, procedural, and strategic. Each of…

3D conductive nanocomposite scaffold for bone tissue engineering

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Shahini A

2013-12-01

Full Text Available Aref Shahini,1 Mostafa Yazdimamaghani,2 Kenneth J Walker,2 Margaret A Eastman,3 Hamed Hatami-Marbini,4 Brenda J Smith,5 John L Ricci,6 Sundar V Madihally,2 Daryoosh Vashaee,1 Lobat Tayebi2,7 1School of Electrical and Computer Engineering, Helmerich Advanced Technology Research Center, 2School of Chemical Engineering, 3Department of Chemistry, 4School of Mechanical and Aerospace Engineering, 5Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; 6Department of Biomaterials and Biomimetics, New York University, New York, NY; 7School of Material Science and Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK, USA Abstract: Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene poly(4-styrene sulfonate (PEDOT:PSS, in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent

Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering

International Nuclear Information System (INIS)

Chen, Chih-Hao; Lee, Ming-Yih; Shyu, Victor Bong-Hang; Chen, Yi-Chieh; Chen, Chien-Tzung; Chen, Jyh-Ping

2014-01-01

Surface modified porous polycaprolactone scaffolds fabricated via rapid prototyping techniques were evaluated for cartilage tissue engineering purposes. Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were surface modified through immersion coating with either gelatin or collagen. Three groups of scaffolds were created and compared for both mechanical and biological properties. Surface modification with collagen or gelatin improved the hydrophilicity, water uptake and mechanical strength of the pristine scaffold. From microscopic observations and biochemical analysis, collagen-modified scaffold was the best for cartilage tissue engineering in terms of cell proliferation and extracellular matrix production. Chondrocytes/collagen-modified scaffold constructs were implanted subdermally in the dorsal spaces of female nude mice. Histological and immunohistochemical staining of the retrieved implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude that collagen surface modification through immersion coating on SLS-manufactured scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial reconstruction. - Highlights: • Selective laser sintered polycaprolactone scaffolds are prepared. • Scaffolds are surface modified through immersion coating with gelatin or collagen. • Collagen-scaffold is the best for cartilage tissue engineering in vitro. • Chondrocytes/collagen-scaffold reveals enhanced cartilage tissue formation in vivo

Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Chen, Chih-Hao [Department of Chemical and Materials Engineering, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Craniofacial Research Center, Chang Gung University, Kweishann, Taoyuan 333, Taiwan, ROC (China); Lee, Ming-Yih [Graduate Institute of Medical Mechatronics, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Shyu, Victor Bong-Hang; Chen, Yi-Chieh; Chen, Chien-Tzung [Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Craniofacial Research Center, Chang Gung University, Kweishann, Taoyuan 333, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan, ROC (China)

2014-07-01

Surface modified porous polycaprolactone scaffolds fabricated via rapid prototyping techniques were evaluated for cartilage tissue engineering purposes. Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were surface modified through immersion coating with either gelatin or collagen. Three groups of scaffolds were created and compared for both mechanical and biological properties. Surface modification with collagen or gelatin improved the hydrophilicity, water uptake and mechanical strength of the pristine scaffold. From microscopic observations and biochemical analysis, collagen-modified scaffold was the best for cartilage tissue engineering in terms of cell proliferation and extracellular matrix production. Chondrocytes/collagen-modified scaffold constructs were implanted subdermally in the dorsal spaces of female nude mice. Histological and immunohistochemical staining of the retrieved implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude that collagen surface modification through immersion coating on SLS-manufactured scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial reconstruction. - Highlights: • Selective laser sintered polycaprolactone scaffolds are prepared. • Scaffolds are surface modified through immersion coating with gelatin or collagen. • Collagen-scaffold is the best for cartilage tissue engineering in vitro. • Chondrocytes/collagen-scaffold reveals enhanced cartilage tissue formation in vivo.

Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics

Science.gov (United States)

Berglund, Björn

2015-01-01

Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment. PMID:26356096

Fabrication and In Vitro Evaluation of Nanosized Hydroxyapatite/Chitosan-Based Tissue Engineering Scaffolds

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Tao Sun

2014-01-01

Full Text Available Composite scaffolds based on biodegradable natural polymer and osteoconductive hydroxyapatite (HA nanoparticles can be promising for a variety of tissue engineering (TE applications. This study addressed the fabrication of three-dimensional (3D porous composite scaffolds composed of HA and chitosan fabricated via thermally induced phase separation and freeze-drying technique. The scaffolds produced were subsequently characterized in terms of microstructure, porosity, and mechanical property. In vitro degradation and in vitro biological evaluation were also investigated. The scaffolds were highly porous and had interconnected pore structures. The pore sizes ranged from several microns to a few hundred microns. The incorporated HA nanoparticles were well mixed and physically coexisted with chitosan in composite scaffold structures. The addition of 10% (w/w HA nanoparticles to chitosan enhanced the compressive mechanical properties of composite scaffold compared to pure chitosan scaffold. In vitro degradation results in phosphate buffered saline (PBS showed slower uptake properties of composite scaffolds. Moreover, the scaffolds showed positive response to mouse fibroblast L929 cells attachment. Overall, the findings suggest that HA/chitosan composite scaffolds could be suitable for TE applications.

Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds

DEFF Research Database (Denmark)

Mygind, Tina; Stiehler, Maik; Baatrup, Anette

2007-01-01

Culture of osteogenic cells on a porous scaffold could offer a new solution to bone grafting using autologous human mesenchymal stem cells (hMSC) from the patient. We compared coralline hydroxyapatite scaffolds with pore sizes of 200 and 500 microm for expansion and differentiation of hMSCs. We...... polymerase chain reaction for 10 osteogenic markers. The 500-microm scaffolds had increased proliferation rates and accommodated a higher number of cells (shown by DNA content, scanning electron microscopy and fluorescence microscopy). Thus the porosity of a 3D microporous biomaterial may be used to steer h......MSC in a particular direction. We found that dynamic spinner flask cultivation of hMSC/scaffold constructs resulted in increased proliferation, differentiation and distribution of cells in scaffolds. Therefore, spinner flask cultivation is an easy-to-use inexpensive system for cultivating hMSCs on small...

Design properties of hydrogel tissue-engineering scaffolds

Science.gov (United States)

Zhu, Junmin; Marchant, Roger E

2011-01-01

This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding. PMID:22026626

Conductive vancomycin-loaded mesoporous silica polypyrrole-based scaffolds for bone regeneration

DEFF Research Database (Denmark)

Zanjanizadeh Ezazi, Nazanin; Shahbazi, Mohammad-Ali; Shatalin, Yuri V.

2018-01-01

-conductive scaffolds. Osteoblast cells were perfectly immersed into the gelatin matrix and remained viable for 14 days. Overall, new conductive composite bone scaffolds were created and the obtained results strongly verified the applicability of this conductive scaffold in drug delivery, encouraging its further...

SIS: a program to generate draft genome sequence scaffolds for prokaryotes

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