A computational and cellular solids approach to the stiffness-based design of bone scaffolds.

Science.gov (United States)

Norato, J A; Wagoner Johnson, A J

2011-09-01

We derive a cellular solids approach to the design of bone scaffolds for stiffness and pore size. Specifically, we focus on scaffolds made of stacked, alternating, orthogonal layers of hydroxyapatite rods, such as those obtained via micro-robotic deposition, and aim to determine the rod diameter, spacing and overlap required to obtain specified elastic moduli and pore size. To validate and calibrate the cellular solids model, we employ a finite element model and determine the effective scaffold moduli via numerical homogenization. In order to perform an efficient, automated execution of the numerical studies, we employ a geometry projection method so that analyses corresponding to different scaffold dimensions can be performed on a fixed, non-conforming mesh. Based on the developed model, we provide design charts to aid in the selection of rod diameter, spacing and overlap to be used in the robotic deposition to attain desired elastic moduli and pore size.

2,2′,3,5′,6-PENTACHLOROBIPHENYL (PCB 95) AND ITS HYDROXYLATED METABOLITES ARE ENANTIOMERICALLY ENRICHED IN FEMALE MICE

Science.gov (United States)

Kania-Korwel, Izabela; Barnhart, Christopher D.; Stamou, Marianna; Truong, Kim M.; El-Komy, Mohammed H.M.E.; Lein, Pamela J.; Veng-Pedersen, Peter; Lehmler, Hans-Joachim

2012-01-01

Epidemiological and laboratory studies link polychlorinated biphenyls and their metabolites to adverse neurodevelopmental outcomes. Several neurotoxic PCB congeners are chiral and undergo enantiomeric enrichment in mammalian species, which may modulate PCB developmental neurotoxicity. This study measures levels and enantiomeric enrichment of PCB 95 and its hydroxylated metabolites (OH-PCBs) in adult female C57Bl/6 mice following subchronic exposure to racemic PCB 95. Tissue levels of PCB 95 and OH-PCBs increased with increasing dose. Dose-dependent enantiomeric enrichment of PCB 95 was observed in brain and other tissues. OH-PCBs also displayed enantiomeric enrichment in blood and liver, but were not detected in adipose and brain. In light of data suggesting enantioselective effects of chiral PCBs on molecular targets linked to PCB developmental neurotoxicity, our observations highlight the importance of accounting for PCB and OH-PCB enantiomeric enrichment in the assessment of PCB developmental neurotoxicity. PMID:22974126

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

Science.gov (United States)

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

"SCAFFOLDING" STUDENTS' WRITING IN EFL CLASS: IMPLEMENTING PROCESS APPROACH

Directory of Open Access Journals (Sweden)

Ekaning Dewanti Laksmi

2006-01-01

Full Text Available The writing process approach views a writing learner as a creator of text, and hence, he needs to experience what writers actually do as they write, and so do students in EFL writing classes. The approach offers an answer to the need of helping the students develop their writing skill without their having to master the basic fundamental elements of writing, i.e. grammar, prior to attending the writing courses. This article highlights the potential of the process approach-with which students go through a write-rewrite process-in giving students a scaffold to work in a real, live process of how a real writer engages in the process of writing. However, the most important harvest is the fact that students have become more confident in expressing their ideas in writings.

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

Validation of a capillary electrophoresis method for the enantiomeric purity testing of ropivacaine, a new local anaesthetic compound

NARCIS (Netherlands)

Sänger-Van De Griend, C. E.; Gröningsson, K.

A capillary electrophoresis method for the determination of the enantiomeric purity of ropivacaine, a new local anaesthetic compound developed by Astra Pain Control AB, has been validated. The method showed the required limit of quantitation of 0.1%, enantiomeric impurity and proved to be robust.

Synthesis of diastereomerically and enantiomerically pure 2,3-disubstituted tetrahydrofurans using a sulfoxonium ylide.

Science.gov (United States)

Schomaker, Jennifer M; Pulgam, Veera Reddy; Borhan, Babak

2004-10-27

Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of enantiomerically pure compounds. In this communication, we describe the use of a Payne rearrangement to control regioselectivity in the ring-opening of a series of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran rings. The factors influencing the success and substitution pattern of the THF ring products are discussed, including steric, electronic, and solvent effects.

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

Microwave-induced biomimetic approach for hydroxyapatite coatings of chitosan scaffolds.

Science.gov (United States)

Kaynak Bayrak, Gökçe; Demirtaş, T Tolga; Gümüşderelioğlu, Menemşe

2017-02-10

Simulated body fluid (SBF) can form calcium phosphates on osteoinductive materials, so it is widely used for coating of bone scaffolds to mimic natural extracellular matrix (ECM). However, difficulties of bulk coating in 3D scaffolds and the necessity of long process times are the common problems for coating with SBF. In the present study, a microwave-assisted process was developed for rapid and internal coating of chitosan scaffolds. The scaffolds were fabricated as superporous hydrogel (SPH) by combining microwave irradiation and gas foaming methods. Then, they were immersed into 10x  SBF-like solution and homogenous bone-like hydroxyapatite (HA) coating was achieved by microwave treatment at 600W without the need of any nucleating agent. Cell culture studies with MC3T3-E1 preosteoblasts showed that microwave-assisted biomimetic HA coating process could be evaluated as an efficient and rapid method to obtain composite scaffolds for bone tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Strategies for osteochondral repair: Focus on scaffolds

Directory of Open Access Journals (Sweden)

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.

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.

Science.gov (United States)

Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M; Jiang, Tao; Wirtel, Anthony J; Deng, Meng; Lv, Qing; Nair, Lakshmi S; Doty, Steven B; Laurencin, Cato T

2008-08-12

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: A combined gene therapy–cell transplantation approach

Science.gov (United States)

Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M.; Jiang, Tao; Wirtel, Anthony J.; Deng, Meng; Lv, Qing; Nair, Lakshmi S.; Doty, Steven B.; Laurencin, Cato T.

2008-01-01

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials. PMID:18678895

3D printed hyperelastic "bone" scaffolds and regional gene therapy: A novel approach to bone healing.

Science.gov (United States)

Alluri, Ram; Jakus, Adam; Bougioukli, Sofia; Pannell, William; Sugiyama, Osamu; Tang, Amy; Shah, Ramille; Lieberman, Jay R

2018-04-01

The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold. In vitro BMP-2 production was assessed using enzyme-linked immunosorbent assay analysis. The ability of ADSCs loaded on the HB scaffold to induce in vivo bone formation in a hind limb muscle pouch model was assessed in the following groups: ADSCs transduced with LV-BMP-2, LV-green fluorescent protein, ADSCs alone, and empty HB scaffolds. Bone formation was assessed using radiographs, histology and histomorphometry. Transduced ADSCs BMP-2 production on the HB scaffold at 24 hours was similar on 3D printed HB scaffolds versus control wells with transduced cells alone, and continued to increase after 1 and 2 weeks of culture. Bone formation was noted in LV-BMP-2 animals on plain radiographs at 2 and 4 weeks after implantation; no bone formation was noted in the other groups. Histology demonstrated that the LV-BMP-2 group was the only group that formed woven bone and the mean bone area/tissue area was significantly greater when compared with the other groups. 3D printed HB scaffolds are effective carriers for transduced ADSCs to promote bone repair. The combination of gene therapy and tissue engineered scaffolds is a promising multidisciplinary approach to bone repair with significant clinical potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1104-1110, 2018. © 2018 Wiley Periodicals, Inc.

Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4.

Science.gov (United States)

Ty, Nancy; Pontikis, Renée; Chabot, Guy G; Devillers, Emmanuelle; Quentin, Lionel; Bourg, Stéphane; Florent, Jean-Claude

2013-03-01

To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (-)-1b, (-)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities. Copyright © 2013. Published by Elsevier Ltd.

Contig-Layout-Authenticator (CLA): A Combinatorial Approach to Ordering and Scaffolding of Bacterial Contigs for Comparative Genomics and Molecular Epidemiology.

Science.gov (United States)

Shaik, Sabiha; Kumar, Narender; Lankapalli, Aditya K; Tiwari, Sumeet K; Baddam, Ramani; Ahmed, Niyaz

2016-01-01

A wide variety of genome sequencing platforms have emerged in the recent past. High-throughput platforms like Illumina and 454 are essentially adaptations of the shotgun approach generating millions of fragmented single or paired sequencing reads. To reconstruct whole genomes, the reads have to be assembled into contigs, which often require further downstream processing. The contigs can be directly ordered according to a reference, scaffolded based on paired read information, or assembled using a combination of the two approaches. While the reference-based approach appears to mask strain-specific information, scaffolding based on paired-end information suffers when repetitive elements longer than the size of the sequencing reads are present in the genome. Sequencing technologies that produce long reads can solve the problems associated with repetitive elements but are not necessarily easily available to researchers. The most common high-throughput technology currently used is the Illumina short read platform. To improve upon the shortcomings associated with the construction of draft genomes with Illumina paired-end sequencing, we developed Contig-Layout-Authenticator (CLA). The CLA pipeline can scaffold reference-sorted contigs based on paired reads, resulting in better assembled genomes. Moreover, CLA also hints at probable misassemblies and contaminations, for the users to cross-check before constructing the consensus draft. The CLA pipeline was designed and trained extensively on various bacterial genome datasets for the ordering and scaffolding of large repetitive contigs. The tool has been validated and compared favorably with other widely-used scaffolding and ordering tools using both simulated and real sequence datasets. CLA is a user friendly tool that requires a single command line input to generate ordered scaffolds.

Use of a macrocyclic antibiotic as the chiral selector for enantiomeric separations by TLC

Energy Technology Data Exchange (ETDEWEB)

Armstrong, D.W.; Zhou, Y. (Univ. of Missouri, Rolla, MO (United States). Dept. of Chemistry)

1994-01-01

The macrocyclic antibiotic, vancomycin, was used as a chiral mobile phase additive for the thin layer chromatographic (TLC) resolution of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatized amino acids, racemic drugs and dansyl-amino acids. Excellent separations were achieved for most of these compounds in the reversed phase mode. Both the nature of the stationary phase and the composition of the mobile phase strongly influenced enantiomeric resolution. The best results were obtained using diphenyl stationary phases. Acetonitrile was the organic modifier that produced the most effective separations with the shortest development times. It is highly likely that macrocyclic antibiotics will play a major role in future enantiomeric separations.

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.

Gas-chromatographic resolution of enantiomeric secondary alcohols. Stereoselective reductive metabolism of ketones in rabbit-liver cytosol.

Science.gov (United States)

Gal, J; DeVito, D; Harper, T W

1981-01-01

Chiral secondary alcohols were treated with (S)-(-)-1-phenylethyl isocyanate. For each racemic alcohol, the resulting diastereomeric urethane derivatives were resolved on flexible fused-silica capillary GLC columns with retention times of 15 min or less. Derivatization of individual enantiomers showed that the urethane derivatives of (R)-(-)-2-octanol, (R)-(+)-1-phenylethyl alcohol, and (S)-(+)-2,2,2-trifluoro-1-phenylethanol are eluted before the corresponding diastereomers. The procedure is simple and rapid, and is suitable for the determination of the enantiomeric composition of chiral alcohols extracted from biological media. A series of aliphatic alcohols, aryl alkyl carbinols, and arylalkyl alkyl carbinols were resolved with the procedure, and the degree of resolution varied from good to excellent. Eight achiral ketones were incubated, individually, with rabbit-liver 90,000 g supernatant fractions, and the enantiomeric composition of the alcohol metabolites was determined with the GLC procedure. The reductions proceeded with high stereoselectivity to give alcohol products of 90% or greater enantiomeric purity. The reduction of 2-octanone and acetophenone gave predominant alcohols of (S)-configuration, in agreement with the Baumann-Prelog rule. The configuration of the predominant alcohols arising in the reduction of the remainder of the ketones could not be firmly established, but the evidence suggests that they are also of the (S)-configuration. Fluorine or methyl substitution in the ortho position of acetophenone produced an increase in the stereoselectivity, and the alcohol produced from ortho-methylacetophenone was enantiomerically greater than 99% pure.

Understanding the effect of amino acids based biostimulant by an enantiomeric analysis of their active principles and a proteomic profiling approach

OpenAIRE

Sierras, Núria; Botta-Català, Anna; Staasing, L.; Martínez Esteso, María José; Bru-Martinez, Roque

2016-01-01

Plant biostimulants are products that contain multiple compounds and claim to activate a wide range of plant responses. Amino acid based products are one example of biostimulants with a complex composition and different product characteristics depending on their sources and production processes. Amino acid biostimulants are obtained mainly by chemical or enzymatic protein hydrolysis and the type of hydrolysis determine the content of free amino acids and their enantiomeric purity. While L-ami...

Enantiomeric profiling of chiral illicit drugs in a pan-European study

NARCIS (Netherlands)

Castrignanò, E.; Yang, Z.; Bade, R.; Baz-Lomba, J.A.; Castiglioni, S.; Causanilles, A.; Covaci, A.; Gracia-Lor, E.; Hernández, F.; Kinyua, J.; McCall, A.-K.; van Nuijs, A.L.N.; Ort, C.; Plósz, B.G.; Ramin, P.; Rousis, N.I.; Ryu, Y.; Thomas, K.V.; de Voogt, P.; Zuccato, E.; Kasprzyk-Hordern, B.

2018-01-01

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their

Production and in vitro characterization of 3D porous scaffolds made of magnesium carbonate apatite (MCA)/anionic collagen using a biomimetic approach

International Nuclear Information System (INIS)

Sader, Marcia S.; Martins, Virginia C.A.; Gomez, Santiago; LeGeros, Racquel Z.; Soares, Gloria A.

2013-01-01

3D porous scaffolds are relevant biomaterials to bone engineering as they can be used as templates to tissue reconstruction. The aim of the present study was to produce and characterize in vitro 3D magnesium-carbonate apatite/collagen (MCA/col) scaffolds. They were prepared by using biomimetic approach, followed by cross-linking with 0.25% glutaraldehyde solution (GA) and liofilization. Results obtained with Fourier-transform infrared spectroscopy (FT-IR) confirmed the type-B carbonate substitution, while by X-ray diffraction (XRD), a crystallite size of ∼ 10 nm was obtained. Optical and electron microscopy showed that the cylindrical samples exhibited an open-porous morphology, with apatite nanocrystals precipitated on collagen fibrils. The cross-linked 3D scaffolds showed integrity when immersed in culture medium up to 14 days. Also, the immersion of such samples into an acid buffer solution, to mimic the osteoclastic resorption environment, promotes the release of important ions for bone repair, such as calcium, phosphorus and magnesium. Bone cells (SaOs2) adhered, and proliferated on the 3D composite scaffolds, showing that synthesis and the cross-linking processes did not induce cytotoxicity. Highlights: • 3D scaffolds of Mg-carbonate–apatite and anionic-collagen were produced. • The biomimetic approach and the cross-linking with 0.25% GA solution were employed. • The scaffolds showed open-porous structure and apatite crystals on collagen fibrils. • The cross-linked scaffolds exhibited integrity when immersed in culture medium. • SaOs2 cells adhered and proliferated on the cross-linked scaffolds confirming no cytotoxicity

Production and in vitro characterization of 3D porous scaffolds made of magnesium carbonate apatite (MCA)/anionic collagen using a biomimetic approach

Energy Technology Data Exchange (ETDEWEB)

Sader, Marcia S., E-mail: msader@metalmat.ufrj.br [Prog. Engenharia Metalúrgica e Materiais, COPPE/UFRJ, RJ (Brazil); Martins, Virginia C.A. [Depto. de Química e Física Molecular, IQSC/USP, SP (Brazil); Gomez, Santiago [Dept. Anatomía Patológica, Universidad de Cádiz, Cadiz (Spain); LeGeros, Racquel Z. [Department of Biomaterials and Biomimetics, New York University College of Dentistry, NY (United States); Soares, Gloria A. [Prog. Engenharia Metalúrgica e Materiais, COPPE/UFRJ, RJ (Brazil)

2013-10-15

3D porous scaffolds are relevant biomaterials to bone engineering as they can be used as templates to tissue reconstruction. The aim of the present study was to produce and characterize in vitro 3D magnesium-carbonate apatite/collagen (MCA/col) scaffolds. They were prepared by using biomimetic approach, followed by cross-linking with 0.25% glutaraldehyde solution (GA) and liofilization. Results obtained with Fourier-transform infrared spectroscopy (FT-IR) confirmed the type-B carbonate substitution, while by X-ray diffraction (XRD), a crystallite size of ∼ 10 nm was obtained. Optical and electron microscopy showed that the cylindrical samples exhibited an open-porous morphology, with apatite nanocrystals precipitated on collagen fibrils. The cross-linked 3D scaffolds showed integrity when immersed in culture medium up to 14 days. Also, the immersion of such samples into an acid buffer solution, to mimic the osteoclastic resorption environment, promotes the release of important ions for bone repair, such as calcium, phosphorus and magnesium. Bone cells (SaOs2) adhered, and proliferated on the 3D composite scaffolds, showing that synthesis and the cross-linking processes did not induce cytotoxicity. Highlights: • 3D scaffolds of Mg-carbonate–apatite and anionic-collagen were produced. • The biomimetic approach and the cross-linking with 0.25% GA solution were employed. • The scaffolds showed open-porous structure and apatite crystals on collagen fibrils. • The cross-linked scaffolds exhibited integrity when immersed in culture medium. • SaOs2 cells adhered and proliferated on the cross-linked scaffolds confirming no cytotoxicity.

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.

The "racemic approach" in the evaluation of the enantiomeric NorA efflux pump inhibition activity of 2-phenylquinoline derivatives.

Science.gov (United States)

Carotti, Andrea; Ianni, Federica; Sabatini, Stefano; Di Michele, Alessandro; Sardella, Roccaldo; Kaatz, Glenn W; Lindner, Wolfgang; Cecchetti, Violetta; Natalini, Benedetto

2016-09-10

Among the mechanisms adopted by bacteria, efflux pumps (EPs) have been recognized as being significantly involved in contributing to resistance to commonly used antibacterial agents. However, little is known about their three-dimensional structures or the steric requirements for their inhibition. Lack of such knowledge includes NorA, one of the most studied Staphylococcus aureus EPs. In the present study, the use of two commercialized Cinchona alkaloid-based zwitterionic chiral stationary phases allowed the enantioseparation of four 2-((2-(4-propoxyphenyl)quinolin-4-yl)oxy)alkylamines 1-4 previously found to be potent S. aureus NorA efflux pump inhibitors when tested as racemates. In the identified optimal polar-ionic conditions (MeOH/THF/H2O-49/49/2 (v/v/v)+25mM formic acid, 12.5mM diethylamine), repeated consecutive injections of 1 allowed the isolation of sufficient amount of its enantiomers (2.6mg and 2.8mg, for (R)-1 and (S)-1, respectively) and then to evaluate their ability to inhibit the S. aureus NorA efflux pump. The biological evaluation highlighted the main contribution of the (R)-1 enantiomer to both the EtBr efflux inhibition and synergistic effect with against SA-1199B (norA+/A116E GrlA) respect to the racemate activity. The comparison between the experimental electronic circular dichroism and the time-dependent density functional theory calculations spectra of the two isolated enantiomeric fractions allowed for all compounds a clear and easy assignment of the enantiomeric elution order. Copyright © 2016 Elsevier B.V. All rights reserved.

Enantiomeric separation of iridium (III) complexes using HPLC chiral stationary phases based on amylose derivatives

International Nuclear Information System (INIS)

Kim, Hee Eun; Seo, Na Hyeon; Hyun, Myung Ho

2016-01-01

Cyclometalated iridium (III) complexes formed with three identical cyclometalating (C-N) ligands (homoleptic) or formed with two cyclometalating (C-N) ligands and one ancillary (LX) ligand (heteroleptic) have been known as highly phosphorescent materials and, thus, they have been utilized as efficient phosphorescent dopants in organic light emitting diodes (OLEDs) 1–3 or as effective phosphorescent chemosensors. 4–7 Cylometalated iridium (III) complexes are chiral compounds consisting of lambda (Λ, left-handed) and delta (Δ, right-handed) isomers. Racemic cyclometa- lated iridium (III) complexes emit light with no net polarization, but optically active cyclometalated iridium (III) complexes emit circularly polarized light. 8,9 Circularly polarized light can be used in various fields including highly efficient three dimensional electronic devices, photo nic devices for optical data storage, biological assays, and others. 8,9 In order to obtain optically active cylometalated iridium (III) complexes and to determine the enantiomeric composition of optically active cylometalated iridium (III) complexes, liquid chromatogr aphic enantiomer separation method on chiral stationary phases (CSPs) has been used. For example, Okamoto and coworkers first reported the high performance liquid chromatographic (HPLC) direct enantiomeric separation of two homoleptic cylometalated iridium (III) complexes on immobilized amylose tris(3,5- dimethylphenylcarbamate) (Chiralpak IA), coated cellulose tris(3,5-dimethylphenylcarbamate) (Chiralc el OD), and coated cellulose tris(4-methylbenzoate) (Chiralce l OJ). 10 Supercritical fluid chromatography (SFC) was also used by Bernhard and coworkers for the enantiomeric separation of cylometalated iridium (III) complexes on coated amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H). 8 However, the general use of the HPLC method for the direct enantiomeric separation of homoleptic

Enantiomeric separation of iridium (III) complexes using HPLC chiral stationary phases based on amylose derivatives

Energy Technology Data Exchange (ETDEWEB)

Kim, Hee Eun; Seo, Na Hyeon; Hyun, Myung Ho [Dept. of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan (Korea, Republic of)

2016-12-15

Cyclometalated iridium (III) complexes formed with three identical cyclometalating (C-N) ligands (homoleptic) or formed with two cyclometalating (C-N) ligands and one ancillary (LX) ligand (heteroleptic) have been known as highly phosphorescent materials and, thus, they have been utilized as efficient phosphorescent dopants in organic light emitting diodes (OLEDs) 1–3 or as effective phosphorescent chemosensors. 4–7 Cylometalated iridium (III) complexes are chiral compounds consisting of lambda (Λ, left-handed) and delta (Δ, right-handed) isomers. Racemic cyclometa- lated iridium (III) complexes emit light with no net polarization, but optically active cyclometalated iridium (III) complexes emit circularly polarized light. 8,9 Circularly polarized light can be used in various fields including highly efficient three dimensional electronic devices, photo nic devices for optical data storage, biological assays, and others. 8,9 In order to obtain optically active cylometalated iridium (III) complexes and to determine the enantiomeric composition of optically active cylometalated iridium (III) complexes, liquid chromatogr aphic enantiomer separation method on chiral stationary phases (CSPs) has been used. For example, Okamoto and coworkers first reported the high performance liquid chromatographic (HPLC) direct enantiomeric separation of two homoleptic cylometalated iridium (III) complexes on immobilized amylose tris(3,5- dimethylphenylcarbamate) (Chiralpak IA), coated cellulose tris(3,5-dimethylphenylcarbamate) (Chiralc el OD), and coated cellulose tris(4-methylbenzoate) (Chiralce l OJ). 10 Supercritical fluid chromatography (SFC) was also used by Bernhard and coworkers for the enantiomeric separation of cylometalated iridium (III) complexes on coated amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H). 8 However, the general use of the HPLC method for the direct enantiomeric separation of homoleptic.

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.

* Comparison of Autologous, Allogeneic, and Cell-Free Scaffold Approaches for Engineered Tendon Repair in a Rabbit Model-A Pilot Study.

Science.gov (United States)

Wang, Wenbo; Deng, Dan; Wang, Bin; Zhou, Guangdong; Zhang, WenJie; Cao, Yilin; Zhang, Peihua; Liu, Wei

2017-08-01

Tendons are subjected to high strength dynamic mechanical forces in vivo. Mechanical strength is an essential requirement for tendon scaffold materials. A composite scaffold was used in this study to provide mechanical strength, which was composed of an inter part of nonwoven polyglycolic acid (PGA) fibers and an outer part of the net knitted with PGA and polylactic acid (PLA) fibers in a ratio of 4:2. This study compared three different approaches for in vivo tendon engineering, that is, cell-free scaffold and allogeneic and autologous cell seeded scaffolds, using a rabbit Achilles tendon repair model. Dermal fibroblasts were, respectively, isolated from the dermis of regular rabbits or green fluorescence protein transgenic rabbits as the autologous and the allogeneic cell sources, respectively. The cell scaffolds and cell-free scaffolds were implanted to bridge a partial segmental defect of rabbit Achilles tendon. The engineered tendons were harvested at 7 and 13 months postsurgery for various examinations. The results showed that all three groups could achieve in vivo tendon regeneration similarly with slightly better tissue formation in autologous group than in other two groups, including better scaffold degradation and relatively thicker collagen fibrils. There were no statistically significant differences in mechanical parameters among three groups. This work demonstrated that allogeneic fibroblasts and scaffold alone are likely to be used for tendon tissue engineering.

Vicinal Diboronates in High Enantiomeric Purity through Tandem Site-Selective NHC–Cu-Catalyzed Boron-Copper Additions to Terminal Alkynes

Science.gov (United States)

Lee, Yunmi; Jang, Hwanjong; Hoveyda, Amir H.

2009-01-01

A Cu-catalyzed protocol for conversion of terminal alkynes to enantiomerically enriched diboronates is reported. In a single vessel, a site-selective hydroboration of an alkyne leads to the corresponding terminal vinylboronate, which undergoes a second site-selective and enantioselective hydroboration. Reactions proceed in the presence of two equivalents of commercially available bis(pinacolato)diboron [B2(pin)2] and 5–7.5 mol % of a chiral bidentate imidazolinium salt, affording diboronates in 60–93% yield and up to 97.5:2.5 enantiomeric ratio (er). The enantiomerically enriched products can be functionalized to afford an assortment of versatile organic molecules. Enynes are converted to unsaturated diboronates with high chemo- (>98% reaction of alkyne; <2% at alkene) and enantioselectivity (e.g., 94.5:5.5 er). PMID:19968273

Production of enantiomerically pure D-Phenylglycine using Pseudomonas aeruginosa 10145 as biocatalyst

Directory of Open Access Journals (Sweden)

F. O. M. Alonso

2008-03-01

Full Text Available Different bacterial strains were screened to detect nitrilase and/or nitrile hidratase/amidase activities towards benzonitrile, to be used as biocatalyst to produce enantiomerically pure non-proteinogenic amino acids using amino nitriles as starting material. The best biocatalyst found was Pseudomonas aeruginosa 10145, which showed high enzyme activities. Whole cells were used as catalyst for the transformation of 2-phenyl-2-amino-acetonitrile for the corresponding D-phenylglycine. The percentage conversion was followed by chiral HPLC. After 1 hour reaction 18% of 2-phenyl-2-amino-acetonitrile was converted into D-phenylglycine with an enantiomeric excess of over 95%. When an inducer was added to the media, an increase in nitrile hydrolyzing activities was detected, hence leading to total conversion of (R-2-phenyl-2-amino-acetonitrile to the corresponding amino acid in 30 min reaction. The isolated yield of the target product was 50% and its characterization was performed by polarimetry, chiral HPLC, IR-FT spectroscopy and GC-MS.

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.

The Synthesis Approach to Analysing Educational Design Dataset: Application of Three Scaffolds to a Learning by Design Task for Postgraduate Education Students

Science.gov (United States)

Thompson, Kate; Carvalho, Lucila; Aditomo, Anindito; Dimitriadis, Yannis; Dyke, Gregory; Evans, Michael A.; Khosronejad, Maryam; Martinez-Maldonado, Roberto; Reimann, Peter; Wardak, Dewa

2015-01-01

The aims of the Synthesis and Scaffolding Project were to understand: the role of specific scaffolds in relation to the activity of learners, and the activity of learners during a collaborative design task from multiple perspectives, through the collection and analysis of multiple streams of data and the adoption of a synthesis approach to the…

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).

Anisotropy Spectra for Enantiomeric Differentiation of Biomolecular Building Blocks

DEFF Research Database (Denmark)

Evans, Amanda C.; Meinert, Cornelia; Bredehoft, Jan H.

2013-01-01

All biopolymers are composed of homochiral building blocks, and both D-sugars and L-amino acids uniquely constitute life on Earth. These monomers were originally enantiomerically differentiated under prebiotic conditions. Particular progress has recently been made in support of the photochemical...... light. This chapter will: (1) present the theory and configuration of anisotropy spectroscopy; (2) explain experimentally recorded anisotropy spectra of selected chiral biomolecules such as amino acids; and (3) discuss the relevance of these spectra for the investigation of the origin of the molecular...

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.

[Studies on origin of illicit methamphetamine. I. The relationship of enantiomeric compositions between methamphetamine and its raw material (ephedrine)].

Science.gov (United States)

Kikura, R; Shimamine, M; Nakahara, Y; Terao, T

1992-01-01

In order to elucidate the relationship of enantiomeric compositions between methamphetamine (MA) and its raw materials, ephedrine (EP) enantiomers, commercial EP samples and MA samples prepared from them were analyzed by HPLC using GITC-prelabeling. The GITC derivatives were separated on ODS column using methanol-water-acetic acid (45:54:1) at a flow rate of 1.2 ml/min for EP and tetrahydrofuran-water-acetic acid (29:70:1) at a flow rate of 1 ml/min for MA. The chromatographic conditions resulted in such a good separation of four EP and two MA enantiomers that 1/1000 enantiomeric impurities could be detected and discriminated from the major enantiomer with good reproducibility. Moreover, it was demonstrated that the asymmetric center at alpha-position of amino group was entirely retained throughout the reductive reaction of the EP samples, and that the MA samples inherited the enantiomeric character from the EP samples used. This method was applied to discriminative analysis of MA samples seized in Japan.

Synthesis and Absolute Configuration of Enantiomerically Pure Vitamin K3 2,3-Epoxide

NARCIS (Netherlands)

Snatzke, Günther; Wijnberg, Hans; Feringa, Bernard; Marsman, Bea G.; Greydanus, Ben; Pluim, Henk

1980-01-01

The 2,3-epoxide of vitamin K3 (menadione, 1) has been prepared in enantiomerically pure form, and the absolute configuration has been deduced from the CD spectrum. The compound with the negative Cotton effect between 340 and 400 nm has the 2R,3S configuration.

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

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.

A simple semi-quantitative approach studying the in vivo degradation of regenerated silk fibroin scaffolds with different pore sizes.

Science.gov (United States)

Guo, Yongwei; Chen, Zhongchun; Wen, Jianchuan; Jia, Minghui; Shao, Zhengzhong; Zhao, Xia

2017-10-01

The biocompatibility and in vivo degradation rate of biomaterials represent critical control points in the long-term success of scaffolds for tissue restoration. In this study, new three-dimensional (3D) regenerated silk fibroin scaffolds (RSFs) were prepared by the freezing-defrosting procedure, and then were implanted beneath the dorsal skin of rats. This study aims to develop a kinetic semi-quantitative approach to assess in vivo degradation rate and biocompatibility of this kind of RSFs with different pore sizes for the first time, and to evaluate the relationship between the biodegradation and tissue responses by measuring the thickness of residual scaffolds, fibrous capsules and infiltrated tissues through integrated techniques of histology, optical imaging and image analysis. Our results showed that scaffolds with both pore sizes (74.35±10.84μm and 139.23±44.93μm, respectively) were well tolerated by host animals and pore size was found to be the rate limiting factor to the biodegradation in the subcutaneous implantation model. In addition, the biodegradation of RSFs was inflammation-mediated to a certain degree and fibroblasts may play a critical role in this process. Overall, such semi-quantitative approach was demonstrated to be a simple and effective method to assess the in vivo degradation rate, and the prepared RSFs were presented to have promising potential in tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

A Systems Approach to Scaffold Communication Skills Development

Science.gov (United States)

Er, Nelson L.

2008-01-01

Objectives To implement a communication skills development (CSD) system and evaluate its effectiveness in a clinical communications course. Design Students conducted baseline interviews and wrote SOAP notes, and based on faculty, patient, self- and peer assessments, set goals for improvement of their communication skills. Students participated in various activities to scaffold their learning, several of which took place in a web-based environment to enhance access and function for both students and faculty members. Quantitative and qualitative analyses were performed. Assessment Students' communication skills improved as evidenced by assessment scores. Student and faculty comments offered additional evidence of the effectiveness of standardized patient interviews, learning strategies, and assessment methods. Conclusion The CSD system effectively integrated various types of learning activities and feedback processes. The use of scaffolding strategies appeared to enhance the development of students' communication skills. PMID:18483601

Progress in scaffold-free bioprinting for cardiovascular medicine.

Science.gov (United States)

Moldovan, Nicanor I

2018-06-01

Biofabrication of tissue analogues is aspiring to become a disruptive technology capable to solve standing biomedical problems, from generation of improved tissue models for drug testing to alleviation of the shortage of organs for transplantation. Arguably, the most powerful tool of this revolution is bioprinting, understood as the assembling of cells with biomaterials in three-dimensional structures. It is less appreciated, however, that bioprinting is not a uniform methodology, but comprises a variety of approaches. These can be broadly classified in two categories, based on the use or not of supporting biomaterials (known as "scaffolds," usually printable hydrogels also called "bioinks"). Importantly, several limitations of scaffold-dependent bioprinting can be avoided by the "scaffold-free" methods. In this overview, we comparatively present these approaches and highlight the rapidly evolving scaffold-free bioprinting, as applied to cardiovascular tissue engineering. © 2018 The Author. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach.

Directory of Open Access Journals (Sweden)

Antonio Boccaccio

Full Text Available Functionally Graded Scaffolds (FGSs are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young's modulus values. For each combination of these variables, the explicit equation of the porosity distribution law-i.e the law that describes the pore dimensions in function of the spatial coordinates-was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards

Homochiral Acyl Isocyanates as Diagnostic NMR Probes for the Enantiomeric Purity of Chiral Alcohols

Directory of Open Access Journals (Sweden)

Gregory H. P. Roos

2000-12-01

Full Text Available The first reported acyl and sulfonylisocyanates were developed and tested in reactions with chiral alcohols to afford diastereomeric carbamates. NMR analysis of these investigates the chemical shift discrimination that would allow these activated isocyanates to be used as diagnostic probes of enantiomeric purity.

Chiral recognition and determination of enantiomeric excess by mass spectrometry: A review

International Nuclear Information System (INIS)

Yu, Xiangying; Yao, Zhong-Ping

2017-01-01

Chiral analysis is of great importance to fundamental and applied research in chemical, biological and pharmaceutical sciences. Due to the superiority of mass spectrometry (MS) over other analytical methods in terms of speed, specificity and sensitivity, chiral analysis by MS has attracted much interest in recent years. Chiral analysis by MS typically involves introduction of a chiral selector to form diastereomers with analyte enantiomers, and comparison of the behaviors of diastereomers in MS. Chiral differentiation can be achieved by comparing the relative abundances of diastereomers, the thermodynamic or kinetic constants of ion-molecule reactions of diastereomers in the gas phase, the dissociation of diastereomers in MS/MS, or the mobility of diastereomers in ion mobility mass spectrometry. In this review, chiral recognition and determination of enantiomeric excess by these chiral MS methods were summarized, and the prospects of chiral analysis by MS were discussed. - Highlights: • Both chiral recognition and determination of enantiomeric excess by mass spectrometry are systematically reviewed. • Classification is based on the behavioral differences of diastereomers formed between chiral analytes and chiral selectors. • Development of ion mobility mass spectrometry for chiral differentiation is covered. • Various methods are highlighted and compared.

Chiral recognition and determination of enantiomeric excess by mass spectrometry: A review

Energy Technology Data Exchange (ETDEWEB)

Yu, Xiangying [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation) and Shenzhen Key Laboratory of Food Biological Safety Control, Shenzhen Research Institute of Hong Kong Polytechnic University, Shenzhen 518057 (China); Yao, Zhong-Ping, E-mail: zhongping.yao@polyu.edu.hk [State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation) and Shenzhen Key Laboratory of Food Biological Safety Control, Shenzhen Research Institute of Hong Kong Polytechnic University, Shenzhen 518057 (China); Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, Jilin (China); State Key Laboratory of Chirosciences, Food Safety and Technology Research Centre and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region (China)

2017-05-22

Chiral analysis is of great importance to fundamental and applied research in chemical, biological and pharmaceutical sciences. Due to the superiority of mass spectrometry (MS) over other analytical methods in terms of speed, specificity and sensitivity, chiral analysis by MS has attracted much interest in recent years. Chiral analysis by MS typically involves introduction of a chiral selector to form diastereomers with analyte enantiomers, and comparison of the behaviors of diastereomers in MS. Chiral differentiation can be achieved by comparing the relative abundances of diastereomers, the thermodynamic or kinetic constants of ion-molecule reactions of diastereomers in the gas phase, the dissociation of diastereomers in MS/MS, or the mobility of diastereomers in ion mobility mass spectrometry. In this review, chiral recognition and determination of enantiomeric excess by these chiral MS methods were summarized, and the prospects of chiral analysis by MS were discussed. - Highlights: • Both chiral recognition and determination of enantiomeric excess by mass spectrometry are systematically reviewed. • Classification is based on the behavioral differences of diastereomers formed between chiral analytes and chiral selectors. • Development of ion mobility mass spectrometry for chiral differentiation is covered. • Various methods are highlighted and compared.

Biomimetic multidirectional scaffolds for zonal osteochondral tissue engineering via a lyophilization bonding approach.

Science.gov (United States)

Clearfield, Drew; Nguyen, Andrew; Wei, Mei

2018-04-01

The zonal organization of osteochondral tissue underlies its long term function. Despite this, tissue engineering strategies targeted for osteochondral repair commonly rely on the use of isotropic biomaterials for tissue reconstruction. There exists a need for a new class of highly biomimetic, anisotropic scaffolds that may allow for the engineering of new tissue with zonal properties. To address this need, we report the facile production of monolithic multidirectional collagen-based scaffolds that recapitulate the zonal structure and composition of osteochondral tissue. First, superficial and osseous zone-mimicking scaffolds were fabricated by unidirectional freeze casting collagen-hyaluronic acid and collagen-hydroxyapatite-containing suspensions, respectively. Following their production, a lyophilization bonding process was used to conjoin these scaffolds with a distinct collagen-hyaluronic acid suspension mimicking the composition of the transition zone. Resulting matrices contained a thin, highly aligned superficial zone that interfaced with a cellular transition zone and vertically oriented calcified cartilage and osseous zones. Confocal microscopy confirmed a zone-specific localization of hyaluronic acid, reflecting the depth-dependent increase of glycosaminoglycans in the native tissue. Poorly crystalline, carbonated hydroxyapatite was localized to the calcified cartilage and osseous zones and bordered the transition zone. Compressive testing of hydrated scaffold zones confirmed an increase of stiffness with scaffold depth, where compressive moduli of chondral and osseous zones fell within or near ranges conducive for chondrogenesis or osteogenesis of mesenchymal stem cells. With the combination of these biomimetic architectural and compositional cues, these multidirectional scaffolds hold great promise for the engineering of zonal osteochondral tissue. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 948-958, 2018. © 2017 Wiley Periodicals

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.

Enantiomeric ratios as an indicator of exposure processes for persistent pollutants in human placentas

DEFF Research Database (Denmark)

Shen, Heqing; Virtanen, H E; Main, Katharina M

2006-01-01

The enantiomeric ratios (ER) of alpha-HCH and o,p'-DDT ((+)-isomer concentration/(-)-isomer concentration) and o,p'-DDD (first eluting enantiomer/second enantiomer) were investigated in 112 human placentas from Finnish boys collected 1997-2001. Both o,p'-DDD and alpha-HCH showed changes in their ER...

Textile-templated electrospun anisotropic scaffolds for regenerative cardiac tissue engineering.

Science.gov (United States)

Şenel Ayaz, H Gözde; Perets, Anat; Ayaz, Hasan; Gilroy, Kyle D; Govindaraj, Muthu; Brookstein, David; Lelkes, Peter I

2014-10-01

For patients with end-stage heart disease, the access to heart transplantation is limited due to the shortage of donor organs and to the potential for rejection of the donated organ. Therefore, current studies focus on bioengineering approaches for creating biomimetic cardiac patches that will assist in restoring cardiac function, by repairing and/or regenerating the intrinsically anisotropic myocardium. In this paper we present a simplified, straightforward approach for creating bioactive anisotropic cardiac patches, based on a combination of bioengineering and textile-manufacturing techniques in concert with nano-biotechnology based tissue-engineering stratagems. Using knitted conventional textiles, made of cotton or polyester yarns as template targets, we successfully electrospun anisotropic three-dimensional scaffolds from poly(lactic-co-glycolic) acid (PLGA), and thermoplastic polycarbonate-urethane (PCU, Bionate(®)). The surface topography and mechanical properties of textile-templated anisotropic scaffolds significantly differed from those of scaffolds electrospun from the same materials onto conventional 2-D flat-target electrospun scaffolds. Anisotropic textile-templated scaffolds electrospun from both PLGA and PCU, supported the adhesion and proliferation of H9C2 cardiac myoblasts cell line, and guided the cardiac tissue-like anisotropic organization of these cells in vitro. All cell-seeded PCU scaffolds exhibited mechanical properties comparable to those of a human heart, but only the cells on the polyester-templated scaffolds exhibited prolonged spontaneous synchronous contractility on the entire engineered construct for 10 days in vitro at a near physiologic frequency of ∼120 bpm. Taken together, the methods described here take advantage of straightforward established textile manufacturing strategies as an efficient and cost-effective approach to engineering 3D anisotropic, elastomeric PCU scaffolds that can serve as a cardiac patch. Copyright �

Toward a Molecular Lego Approach for the Diversity-Oriented Synthesis of Cyclodextrin Analogues Designed as Scaffolds for Multivalent Systems.

Science.gov (United States)

Lepage, Mathieu L; Schneider, Jérémy P; Bodlenner, Anne; Compain, Philippe

2015-11-06

A modular strategy has been developed to access a diversity of cyclic and acyclic oligosaccharide analogues designed as prefunctionalized scaffolds for the synthesis of multivalent ligands. This convergent approach is based on bifunctional sugar building blocks with two temporarily masked functionalities that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated as a free alkyne and masked as a triethylsilyl-alkyne. Following a cyclooligomerization approach, the first examples of close analogues of cyclodextrins composed of d-glucose residues and triazole units bound together through α-(1,4) linkages were obtained. The cycloglucopyranoside analogue containing four sugar units was used as a template to prepare multivalent systems displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On the other hand, the modular approach led to acyclic alkyne-functionalized scaffolds of a controlled size that were used to synthesize multivalent iminosugars.

Scaffolds in regenerative endodontics: A review

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

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

Influence of crosslinking on the mechanical behavior of 3D printed alginate scaffolds: Experimental and numerical approaches.

Science.gov (United States)

Naghieh, Saman; Karamooz-Ravari, Mohammad Reza; Sarker, M D; Karki, Eva; Chen, Xiongbiao

2018-04-01

Tissue scaffolds fabricated by three-dimensional (3D) bioprinting are attracting considerable attention for tissue engineering applications. Because the mechanical properties of hydrogel scaffolds should match the damaged tissue, changing various parameters during 3D bioprinting has been studied to manipulate the mechanical behavior of the resulting scaffolds. Crosslinking scaffolds using a cation solution (such as CaCl 2 ) is also important for regulating the mechanical properties, but has not been well documented in the literature. Here, the effect of varied crosslinking agent volume and crosslinking time on the mechanical behavior of 3D bioplotted alginate scaffolds was evaluated using both experimental and numerical methods. Compression tests were used to measure the elastic modulus of each scaffold, then a finite element model was developed and a power model used to predict scaffold mechanical behavior. Results showed that crosslinking time and volume of crosslinker both play a decisive role in modulating the mechanical properties of 3D bioplotted scaffolds. Because mechanical properties of scaffolds can affect cell response, the findings of this study can be implemented to modulate the elastic modulus of scaffolds according to the intended application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fabrication of metallic biomedical scaffolds with the space holder method : A review

NARCIS (Netherlands)

Arifvianto, B.; Zhou, J.

2014-01-01

Bone tissue engineering has been increasingly studied as an alternative approach to bone defect reconstruction. In this approach, new bone cells are stimulated to grow and heal the defect with the aid of a scaffold that serves as a medium for bone cell formation and growth. Scaffolds made of

Fabrication and Mechanical Characterization of Hydrogel Infused Network Silk Scaffolds

Directory of Open Access Journals (Sweden)

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.

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

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.

Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

Science.gov (United States)

Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi

2015-05-01

Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

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

Directory of Open Access Journals (Sweden)

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.

Calcium phosphate coated Keratin-PCL scaffolds for potential bone tissue regeneration.

Science.gov (United States)

Zhao, Xinxin; Lui, Yuan Siang; Choo, Caleb Kai Chuen; Sow, Wan Ting; Huang, Charlotte Liwen; Ng, Kee Woei; Tan, Lay Poh; Loo, Joachim Say Chye

2015-04-01

The incorporation of hydroxyapatite (HA) nanoparticles within or on the surface of electrospun polymeric scaffolds is a popular approach for bone tissue engineering. However, the fabrication of osteoconductive composite scaffolds via benign processing conditions still remains a major challenge to date. In this work, a new method was developed to achieve a uniform coating of calcium phosphate (CaP) onto electrospun keratin-polycaprolactone composites (Keratin-PCL). Keratin within PCL was crosslinked to decrease its solubility, before coating of CaP. A homogeneous coating was achieved within a short time frame (~10min) by immersing the scaffolds into Ca(2+) and (PO4)(3-) solutions separately. Results showed that the incorporation of keratin into PCL scaffolds not only provided nucleation sites for Ca(2+) adsorption and subsequent homogeneous CaP surface deposition, but also facilitated cell-matrix interactions. An improvement in the mechanical strength of the resultant composite scaffold, as compared to other conventional coating methods, was also observed. This approach of developing a biocompatible bone tissue engineering scaffold would be adopted for further in vitro osteogenic differentiation studies in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Enantiomeric profiling of a chemically diverse mixture of chiral pharmaceuticals in urban water

International Nuclear Information System (INIS)

Evans, S.; Bagnall, J.; Kasprzyk-Hordern, B.

2017-01-01

Due to concerns regarding the release of pharmaceuticals into the environment and the understudied impact of stereochemistry of pharmaceuticals on their fate and biological potency, we focussed in this paper on stereoselective transformation pathways of selected chiral pharmaceuticals (16 pairs) at both microcosm (receiving waters and activated sludge wastewater treatment simulating microcosms) and macrocosm (wastewater treatment plant (WWTP) utilising activated sludge technology and receiving waters) scales in order to test the hypothesis that biodegradation of chiral drugs is stereoselective. Our monitoring programme of a full scale activated sludge WWTP and receiving environment revealed that several chiral drugs, those being marketed mostly as racemates, are present in wastewater and receiving waters enriched with one enantiomeric form (e.g. fluoxetine, mirtazapine, salbutamol, MDMA). This is most likely due to biological metabolic processes occurring in humans and other organisms. Both activated sludge and receiving waters simulating microcosms confirmed our hypothesis that chiral drugs are subject to stereoselective microbial degradation. It led, in this research, to preferential degradation of S-(+)-enantiomers of amphetamines, R-(+)-enantiomers of beta-blockers and S-(+)-enantiomers of antidepressants. In the case of three parent compound – metabolite pairs (venlafaxine – desmethylvenlafaxine, citalopram – desmethylcitalopram and MDMA - MDA), while parent compounds showed higher resistance to both microbial metabolism and photodegradation, their desmethyl metabolites showed much higher degradation rate both in terms of stereoselective metabolic and non-stereoselective photochemical processes. It is also worth noting that metabolites tend to be, as expected, enriched with enantiomers of opposite configuration to their parent compounds, which might have significant toxicological consequences when evaluating the metabolic residues of chiral pollutants

Fabrication of triple-layered bifurcated vascular scaffold with a certain degree of three-dimensional structure

Science.gov (United States)

Liu, Yuanyuan; Jiang, Weijian; Yang, Yang; Pu, Huayan; Peng, Yan; Xin, Liming; Zhang, Yi; Sun, Yu

2018-01-01

Constructing vascular scaffolds is important in tissue engineering. However, scaffolds with characteristics such as multiple layers and a certain degree of spatial morphology still cannot be readily constructed by current vascular scaffolds fabrication techniques. This paper presents a three-layered bifurcated vascular scaffold with a curved structure. The technique combines 3D printed molds and casting hydrogel and fugitive ink to create vessel-mimicking constructs with customizable structural parameters. Compared with other fabrication methods, the technique can create more native-like 3D geometries. The diameter and wall thickness of the fabricated constructs can be independently controlled, providing a feasible approach for vascular scaffold construction. Enzymatically-crosslinked gelatin was used as the scaffold material. The morphology and mechanical properties were evaluated. Human umbilical cord derived endothelial cells (HUVECs) were seeded on the scaffolds and cultured for 72 h. Cell viability and morphology were assessed. The results showed that the proposed process had good application potentials, and will hopefully provide a feasible approach for constructing vascular scaffolds.

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/ ).

Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

Science.gov (United States)

Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

2007-04-01

Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic

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

Science.gov (United States)

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.

Synthesis of radiolabeled racemic and enantiomeric antiarrhythmic agents

Energy Technology Data Exchange (ETDEWEB)

Stolle, W.T.; Stelzer, L.S.; Hester, J.B.; Perricone, S.C.; Hsi, R.S.P. (Upjohn Co., Kalamazoo, MI (United States))

1994-10-01

Ibutilide fumarate, racemic N-[4-[4-(ethyl-n-heptylamino)-hydroxybutyl]phenyl]methanesulfonamide hemifumarate, and artilide, the R-(+)-enantiomer of N-[4-[4-(ethyl-n-heptylamino)-hydroxybutyl]phenyl]methanesulfonamide hemifumerate, are under clinical investigation as Class III antiarrhythmic agents. For conducting drug disposition studies, we synthesized carbon-14 labeled ibutilide, as well as its two enantiomeric forms. In addition, high specific activity tritium labeled ibutilide was also prepared to facilitate development of a radioimmunoassay and for studying receptor site characteristics of this agent. Results of metabolism studies with [[sup 14]C]ibutilide led us to prepare tritium labeled artilide, which is more readily accessible than the C-14 labeled drug. The optical antipode of artilide was also labeled with tritium for comparative drug disposition investigations on the two enantiomers. (author).

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

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.

Science.gov (United States)

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.

Scaffolding the design of accessible eLearning content: a user-centered approach and cognitive perspective.

Science.gov (United States)

Catarci, Tiziana; De Giovanni, Loredana; Gabrielli, Silvia; Kimani, Stephen; Mirabella, Valeria

2008-08-01

There exist various guidelines for facilitating the design, preparation, and deployment of accessible eLearning applications and contents. However, such guidelines prevalently address accessibility in a rather technical sense, without giving sufficient consideration to the cognitive aspects and issues related to the use of eLearning materials by learners with disabilities. In this paper we describe how a user-centered design process was applied to develop a method and set of guidelines for didactical experts to scaffold their creation of accessible eLearning content, based on a more sound approach to accessibility. The paper also discusses possible design solutions for tools supporting eLearning content authors in the adoption and application of the proposed approach.

Combining technologies to create bioactive hybrid scaffolds for bone tissue engineering.

Science.gov (United States)

Nandakumar, Anandkumar; Barradas, Ana; de Boer, Jan; Moroni, Lorenzo; van Blitterswijk, Clemens; Habibovic, Pamela

2013-01-01

Combining technologies to engineer scaffolds that can offer physical and chemical cues to cells is an attractive approach in tissue engineering and regenerative medicine. In this study, we have fabricated polymer-ceramic hybrid scaffolds for bone regeneration by combining rapid prototyping (RP), electrospinning (ESP) and a biomimetic coating method in order to provide mechanical support and a physico-chemical environment mimicking both the organic and inorganic phases of bone extracellular matrix (ECM). Poly(ethylene oxide terephthalate)-poly(buthylene terephthalate) (PEOT/PBT) block copolymer was used to produce three dimensional scaffolds by combining 3D fiber (3DF) deposition, and ESP, and these constructs were then coated with a Ca-P layer in a simulated physiological solution. Scaffold morphology and composition were studied using scanning electron microscopy (SEM) coupled to energy dispersive X-ray analyzer (EDX) and Fourier Tranform Infrared Spectroscopy (FTIR). Bone marrow derived human mesenchymal stromal cells (hMSCs) were cultured on coated and uncoated 3DF and 3DF + ESP scaffolds for up to 21 d in basic and mineralization medium and cell attachment, proliferation, and expression of genes related to osteogenesis were assessed. Cells attached, proliferated and secreted ECM on all the scaffolds. There were no significant differences in metabolic activity among the different groups on days 7 and 21. Coated 3DF scaffolds showed a significantly higher DNA amount in basic medium at 21 d compared with the coated 3DF + ESP scaffolds, whereas in mineralization medium, the presence of coating in 3DF+ESP scaffolds led to a significant decrease in the amount of DNA. An effect of combining different scaffolding technologies and material types on expression of a number of osteogenic markers (cbfa1, BMP-2, OP, OC and ON) was observed, suggesting the potential use of this approach in bone tissue engineering.

A novel nano-hydroxyapatite — PMMA hybrid scaffolds adopted by conjugated thermal induced phase separation (TIPS) and wet-chemical approach: Analysis of its mechanical and biological properties

Energy Technology Data Exchange (ETDEWEB)

G, Radha [National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai 600025 (India); S, Balakumar, E-mail: balasuga@yahoo.com [National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai 600025 (India); Venkatesan, Balaji; Vellaichamy, Elangovan [Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025 (India)

2017-06-01

In this study, we report the preparation of nano-hydroxyapatite (nHAp) incorporated poly(methyl methacrylate) (PMMA) scaffolds by conjugated thermal induced phase separation (TIPS) and wet-chemical approach, which essentially facilitates the enhancement of both mechanical as well as biological properties of the scaffolds. The dissolution of PMMA was accomplished by acetone (Ace scaffold), ethanol-water (E-W scaffold) and isopropanol-water (I-W scaffold) mixtures as solvents. The existence of nHAp in PMMA matrix was investigated systematically. The higher degree of porous architecture was achieved from Ace scaffolds compared to both I-W and E-W scaffolds. On the other hand, the dense porous architecture of the I-W scaffold exhibited superior hardness and compressive strength than that of the Ace and E-W scaffolds. All the fabricated samples demonstrated enhanced in vitro bioactivity with respect to increasing immersion period as a result of flower-like in vitro apatite layer formation. The MTT assay was carried out for 1 day and 3 day culture using Saos-2 osteoblast-like cells, which showed better cell proliferation with increasing culture period owing to the interconnected pore architecture of scaffolds and the rational hemocompatibility as per the ASTM standard F756-00. - Highlights: • Conjugated TIPS – wet chemical derived strategy was adopted for PMMA-nHAp composite scaffolds preparation. • TIPS method was carried out by varying solvents such as acetone, isopropanol-water and ethanol-water mixtures. • The impact of solvents on porosity and mechanical properties has been explored. • The existence of nHAp in PMMA has improved in-vitro bioactivity through apatitic-flowers formation. • Hemocompatibility of the scaffolds are in agreement with ASTM standards.

HSCCC separation and enantiomeric distribution of key volatile constituents of Piper claussenianum (Miq.) C. DC. (Piperaceae).

Science.gov (United States)

Marques, André M; Fingolo, Catharina E; Kaplan, Maria Auxiliadora C

2017-11-01

High Speed Countercurrent Chromatography (HSCCC) technique was used for the preparative isolation of the major leishmanicidal compounds from the essential oils of Piper claussenianum species in Brazil. The essential oils from inflorescences of P. claussenianum were analyzed by GC-FID and GC-MS. The enantiomeric ratio of the major constituents of the P. claussenianum essential oils were determined using a Rt-DEXsm chiral capillary column by GC-FID analysis. It was found an enantiomeric excess of (+)-(E)-nerolidol in the leaves, and (+)-linalool and (+)-(E)-nerolidol in the inflorescences essential oil. The major volatile terpenes alcohols were isolated in preparative scale from inflorescences: linalool (320.0 mg) and nerolidol (95.0 mg) in high purity level. The HSCCC, a support-free liquid-liquid partition chromatographic technique, proved to be an effective and useful method for fast isolation and purification of hydrophobic and similarly structured bioactive components from essential oils of Piper species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines

Science.gov (United States)

2015-01-01

Chemoenzymatic dynamic kinetic resolution (DKR) constitutes a convenient and efficient method to access enantiomerically pure alcohol and amine derivatives. This Perspective highlights the work carried out within this field during the past two decades and pinpoints important avenues for future research. First, the Perspective will summarize the more developed area of alcohol DKR, by delineating the way from the earliest proof-of-concept protocols to the current state-of-the-art systems that allows for the highly efficient and selective preparation of a wide range of enantiomerically pure alcohol derivatives. Thereafter, the Perspective will focus on the more challenging DKR of amines, by presenting the currently available homogeneous and heterogeneous methods and their respective limitations. In these two parts, significant attention will be dedicated to the design of efficient racemization methods as an important means of developing milder DKR protocols. In the final part of the Perspective, a brief overview of the research that has been devoted toward improving enzymes as biocatalysts is presented. PMID:25730714

Development and characterization of a PHB-HV-based 3D scaffold for a tissue engineering and cell-therapy combinatorial approach for spinal cord injury regeneration.

Science.gov (United States)

Ribeiro-Samy, Silvina; Silva, Nuno A; Correlo, Vitor M; Fraga, Joana S; Pinto, Luísa; Teixeira-Castro, Andreia; Leite-Almeida, Hugo; Almeida, Armando; Gimble, Jeffrey M; Sousa, Nuno; Salgado, António J; Reis, Rui L

2013-11-01

Spinal cord injury (SCI) leads to devastating neurological deficits. Several tissue engineering (TE)-based approaches have been investigated for repairing this condition. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found to be particularly attractive for TE applications due to its properties, such as biodegradability, biocompatibility, thermoplasticity and piezoelectricity. Hence, this report addresses the development and characterization of PHB-HV-based 3D scaffolds, produced by freeze-drying, aimed to SCI treatment. The obtained scaffolds reveal an anisotropic morphology with a fully interconnected network of pores. In vitro studies demonstrate a lack of cytotoxic effect of PHB-HV scaffolds. Direct contact assays also reveal their ability to support the culture of CNS-derived cells and mesenchymal-like stem cells from different sources. Finally, histocompatibility studies show that PHB-HV scaffolds are well tolerated by the host tissue, and do not negatively impact the left hindlimb locomotor function recovery. Therefore results herein presented suggest that PHB-HV scaffolds may be suitable for SCI treatment. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[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

Fabrication of computationally designed scaffolds by low temperature 3D printing

International Nuclear Information System (INIS)

Castilho, Miguel; Dias, Marta; Fernandes, Paulo; Pires, Inês; Gouveia, Barbara; Rodrigues, Jorge; Gbureck, Uwe; Groll, Jürgen; Vorndran, Elke

2013-01-01

The development of artificial bone substitutes that mimic the properties of bone and simultaneously promote the desired tissue regeneration is a current issue in bone tissue engineering research. An approach to create scaffolds with such characteristics is based on the combination of novel design and additive manufacturing processes. The objective of this work is to characterize the microstructural and the mechanical properties of scaffolds developed by coupling both topology optimization and a low temperature 3D printing process. The scaffold design was obtained using a topology optimization approach to maximize the permeability with constraints on the mechanical properties. This procedure was studied to be suitable for the fabrication of a cage prototype for tibial tuberosity advancement application, which is one of the most recent and promising techniques to treat cruciate ligament rupture in dogs. The microstructural and mechanical properties of the scaffolds manufactured by reacting α/β-tricalcium phosphate with diluted phosphoric acid were then assessed experimentally and the scaffolds strength reliability was determined. The results demonstrate that the low temperature 3D printing process is a reliable option to create synthetic scaffolds with tailored properties, and when coupled with topology optimization design it can be a powerful tool for the fabrication of patient-specific bone implants. (paper)

Combining technologies to create bioactive hybrid scaffolds for bone tissue engineering

NARCIS (Netherlands)

Nandakumar, A.; Barradas, A.M.C.; de Boer, Jan; Moroni, Lorenzo; van Blitterswijk, Clemens; Habibovic, Pamela

2013-01-01

Combining technologies to engineer scaffolds that can offer physical and chemical cues to cells is an attractive approach in tissue engineering and regenerative medicine. In this study, we have fabricated polymer-ceramic hybrid scaffolds for bone regeneration by combining rapid prototyping (RP),

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.

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

Tris[(6S)-6-hy-droxy-4-epi-shikimic acid] monohydrate: an enanti-omerically pure hy-droxy-lated shikimic acid derived from methyl shikimate.

Science.gov (United States)

Griesbeck, Axel G; Miara, Claus; Neudörfl, Jörg-M

2012-11-01

The title compound, 3C(7)H(10)O(6)·H(2)O, is the enanti-omerically pure product of a multi-step synthesis from the enanti-omerically pure natural shikimic acid. The asymmetric unit contains three mol-ecules of the acid and one mol-ecule of water. The cyclo-hexene rings of the acids have half-chair conformations. The carboxyl-ate, the four hydroxide groups and the additional water mol-ecule form a complex three-dimensional hydrogen-bonding network.

A novel nano-hydroxyapatite – PMMA hybrid scaffolds adopted by conjugated thermal induced phase separation (TIPS) and wet-chemical approach: Analysis of its mechanical and biological properties

Energy Technology Data Exchange (ETDEWEB)

Radha, G. [National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy campus, Chennai 600025 (India); Balakumar, S., E-mail: balasuga@yahoo.com [National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy campus, Chennai 600025 (India); Venkatesan, Balaji; Vellaichamy, Elangovan [Department of Biochemistry, University of Madras, Guindy campus, Chennai 600025 (India)

2017-04-01

In this study, we report the preparation of nano-hydroxyapatite (nHAp) incorporated poly(methyl methacrylate) (PMMA) scaffolds by conjugated thermal induced phase separation (TIPS) and wet-chemical approach, which essentially facilitates the enhancement of both mechanical as well as biological properties of the scaffolds. The dissolution of PMMA was accomplished by acetone (Ace scaffold), ethanol-water (E-W scaffold) and isopropanol-water (I-W scaffold) mixtures as solvents. The existence of nHAp in PMMA matrix was investigated systematically. The porosity of ~ 57.89% was achieved from Ace scaffold that was higher degree compared to both I-W and E-W scaffolds. On the other hand, the dense porous architecture of I-W scaffold exhibited superior hardness of ~ 65.6 HR ‘D’ than that of the Ace and E-W scaffolds. All the fabricated samples demonstrated enhanced in vitro bioactivity with respect to increasing immersion period as a result of flower-like in vitro apatite layer formation. The MTT assay was carried out for 1 day and 3 day culture using Saos-2 osteoblast-like cells, which showed better cell proliferation with increasing culture period owing to the interconnected pore architecture of scaffolds and the rational hemocompatibility as per the ASTM standard F756-00. - Highlights: • Conjugated TIPS – wet chemical derived strategy was adopted for PMMA-nHAp composite scaffolds preparation. • TIPS method was carried out by varying solvents such as acetone, isopropanol-water and ethanol-water mixtures. • The impact of solvents on porosity and mechanical properties has been explored. • The existence of nHAp in PMMA has improved in-vitro bioactivity through apatitic-flowers formation. • Hemocompatibility of the scaffolds are in agreement with ASTM standards.

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

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.

Enantiomeric fraction and isomeric composition to assess sources of DDT residues in soils.

Science.gov (United States)

Bosch, Carme; Grimalt, Joan O; Fernández, Pilar

2015-11-01

Chiral pesticides such as o,p'-DDT can undergo enantioselective microbial degradation in soil. Hence, the enantiomeric fraction (EF) of o,p'-DDT was used as an approach to assess potential recent inputs of DDT in the lower part of the Ebro River basin (NE Spain), a region heavily impacted by agricultural and industrial activities, including a dicofol production and a chloro-alkali plants. The EFs of five out of nineteen soils were not different from the racemic value (0.505±0.010), confirming that the Ebro River and some of its tributaries, Segre and Cinca rivers, transported fresh DDT residues despite its ban in Spain during the 90 s. o,p'-DDT/p,p'-DDT ratios in soils suggest that recent use of technical DDT and/or DDT-contaminated dicofol may be responsible for the fresh DDT inputs in the Segre River, while in the Ebro River, they indicate a dominant contribution of technical DDT, likely related to the residues accumulated by the chloro-alkali plant discharges. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery.

Science.gov (United States)

Ceccarelli, Gabriele; Presta, Rossella; Benedetti, Laura; Cusella De Angelis, Maria Gabriella; Lupi, Saturnino Marco; Rodriguez Y Baena, Ruggero

2017-01-01

Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives) or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone). This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery

Directory of Open Access Journals (Sweden)

Gabriele Ceccarelli

2017-01-01

Full Text Available Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA, polylactic acid (PLA, and polycaprolactone. This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.

Visualizing feasible operating ranges within tissue engineering systems using a "windows of operation" approach: a perfusion-scaffold bioreactor case study.

Science.gov (United States)

McCoy, Ryan J; O'Brien, Fergal J

2012-12-01

Tissue engineering approaches to developing functional substitutes are often highly complex, multivariate systems where many aspects of the biomaterials, bio-regulatory factors or cell sources may be controlled in an effort to enhance tissue formation. Furthermore, success is based on multiple performance criteria reflecting both the quantity and quality of the tissue produced. Managing the trade-offs between different performance criteria is a challenge. A "windows of operation" tool that graphically represents feasible operating spaces to achieve user-defined levels of performance has previously been described by researchers in the bio-processing industry. This paper demonstrates the value of "windows of operation" to the tissue engineering field using a perfusion-scaffold bioreactor system as a case study. In our laboratory, perfusion bioreactor systems are utilized in the context of bone tissue engineering to enhance the osteogenic differentiation of cell-seeded scaffolds. A key challenge of such perfusion bioreactor systems is to maximize the induction of osteogenesis but minimize cell detachment from the scaffold. Two key operating variables that influence these performance criteria are the mean scaffold pore size and flow-rate. Using cyclooxygenase-2 and osteopontin gene expression levels as surrogate indicators of osteogenesis, we employed the "windows of operation" methodology to rapidly identify feasible operating ranges for the mean scaffold pore size and flow-rate that achieved user-defined levels of performance for cell detachment and differentiation. Incorporation of such tools into the tissue engineer's armory will hopefully yield a greater understanding of the highly complex systems used and help aid decision making in future translation of products from the bench top to the market place. Copyright © 2012 Wiley Periodicals, Inc.

Fabrication of orderly nanostructured PLGA scaffolds using anodic aluminum oxide templates.

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Wang, Gou-Jen; Lin, Yan-Cheng; Li, Ching-Wen; Hsueh, Cheng-Chih; Hsu, Shan-Hui; Hung, Huey-Shan

2009-08-01

In this research, two simple fabrication methods to fabricate orderly nanostructured PLGA scaffolds using anodic aluminum oxide (AAO) template were conducted. In the vacuum air-extraction approach, the PLGA solution was cast on an AAO template first. The vacuum air-extraction process was then applied to suck the semi-congealed PLGA into the nanopores of the AAO template to form a bamboo sprouts array of PLGA. The surface roughness of the nanostructured scaffolds, ranging from 20 nm to 76 nm, can be controlled by the sucking time of the vacuum air-extraction process. In the replica molding approach, the PLGA solution was cast on the orderly scraggy barrier-layer surface of an AAO membrane to fabricate a PLGA scaffold of concave nanostructure. Cell culture experiments using the bovine endothelial cells (BEC) demonstrated that the nanostructured PLGA membrane can increase the cell growing rate, especially for the bamboo sprouts array scaffolds with smaller surface roughness.

Scaffolding EFL Students' Writing through the Writing Process Approach

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Faraj, Avan Kamal Aziz

2015-01-01

This research reports a study conducted at Koya University/English Language Department, and it aims at presenting the effect of scaffolding on EFL students' writing ability through the writing process. In this study, the students have taken the role of writers, so they need to follow the same steps that writers apply during their writing process.…

Scaffolding Teachers Integrate Social Media Into a Problem‑Based Learning Approach?

DEFF Research Database (Denmark)

Buus, Lillian

2012-01-01

to develop design specifications and/or early prototypes within a few hours of starting work. In order to achieve one of the objectives of my PhD, I aim to further developing and elaborate on this method, which hopefully will lead to a pedagogical design method scaffolding teachers in their learning designs......At Aalborg University (AAU) we are known to work with problem‑based learning (PBL) in a particular way designated “The Aalborg PBL model”. In PBL the focus is on participant control, knowledge sharing, collaboration among participants, which makes it interesting to consider the integration...... to learning design when combining the PBL approach with social media or web 2.0 activities or/and technologies. With regard to the discussions about PBL, three important characteristics of PBL can be extracted; the problem, the work process, and the solution, which can be used to distinguish between various...

Enantiomeric determination of amino compounds with high sensitivity using the chiral reagents (+)- and (-)-1-(9-anthryl)-2-propyl chloroformate.

Science.gov (United States)

Thorsén, G; Engström, A; Josefsson, B

1997-10-31

New chiral precolumn reagents, (+)- and (-)-1-(9-anthryl)-2-propyl chloroformate (APOC), are introduced for the chiral separation of amino acids and small peptides in capillary electrophoresis. Chiral separation of 17 amino acids and four small peptides as their diastereomeric 1-(9-anthryl)-2-propyl carbamate derivatives have been achieved by micellar electrokinetic chromatography. The detection limit for the derivatives is in the femtomole range with UV detection and in the attomole range with laser-induced fluorescence (LIF) detection. LIF detection was used to determine the enantiomeric excess of four APOC-derivatised peptides. The use of the new, anthracene-based reagents in conjunction with argon ion LIF makes enantiomeric determinations at ppm levels feasible. In this paper determinations below promille levels are performed without overloading the separation system.

Acellular organ scaffolds for tumor tissue engineering

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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.

3D Printed Silicone–Hydrogel Scaffold with Enhanced Physicochemical Properties

DEFF Research Database (Denmark)

Mohanty, Soumyaranjan; Alm, Martin; Hemmingsen, Mette

2016-01-01

is currently a huge challenge. The goal of this work was to fabricate a tissue engineering scaffold from clinically approved materials with the capability of delivering biomolecules and direct cell fate. We have used a simple 3D printing approach, that combines polymer casting with supercritical fluid...... technology to produce 3D interpenetrating polymer network (IPN) scaffold of silicone-poly(2-hydroxyethyl methacrylate)-co-poly(ethylene glycol) methyl ether acrylate (pHEMA-co-PEGMEA). The pHEMA-co-PEGMEA IPN materials were employed to support growth of human mesenchymal stem cells (hMSC), resulting in high...... cell viability and metabolic activity over a 3 weeks period. In addition, the IPN scaffolds support 3D tissue formation inside the porous scaffold with well spread cell morphology on the surface of the scaffold. As a proof of concept, sustained doxycycline (DOX) release from pHEMA-co-PEGMEA IPN...

Biomimetic mineral-organic composite scaffolds with controlled internal architecture.

Science.gov (United States)

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.

Treatment of Oral Biofilms by a D-Enantiomeric Peptide.

Science.gov (United States)

Zhang, Tian; Wang, Zhejun; Hancock, Robert E W; de la Fuente-Núñez, César; Haapasalo, Markus

2016-01-01

Almost all dental diseases are caused by biofilms that consist of multispecies communities. DJK-5, which is a short D-enantiomeric, protease-resistant peptide with broad-spectrum anti-biofilm activity, was tested for its effect on oral multispecies biofilms. Peptide DJK-5 at 10 μg/mL effectively prevented the growth of these microbes in culture media in a time-dependent manner. In addition to the prevention of growth, peptide DJK-5 completely killed both Streptococcus mutans and Enterococcus faecalis suspended from biofilms after 30 minutes of incubation in liquid culture media. DJK-5 also led to the effective killing of microbes in plaque biofilm. The proportion of bacterial cells killed by 10 μg/mL of DJK-5 was similar after 1 and 3 days, both exceeding 85%. DJK-5 was able to significantly prevent biofilm formation over 3 days (P = 0.000). After 72 hours of exposure, DJK-5 significantly reduced and almost completely prevented plaque biofilm production by more than 90% of biovolume compared to untreated controls (P = 0.000). The proportion of dead biofilm bacteria at the 10 μg/mL DJK-5 concentration was similar for 1- and 3-day-old biofilms, whereby >86% of the bacteria were killed. DJK-5 was also able to kill >79% and >85% of bacteria, respectively, after one-time and three brief treatments of 3-day-old biofilms. The combination of DJK-5 and chlorhexidine showed the best bacterial killing among all treatments, with ~83% and >88% of bacterial cells killed after 1 and 3 minutes, respectively. No significant difference was found in the percentage of biofilm killing amongst three donor plaque samples after DJK-5 treatment. In particular, DJK-5 showed strong performance in inhibiting biofilm development and eradicating pre-formed oral biofilms compared to L-enantiomeric peptide 1018. DJK-5 was very effective against oral biofilms when used alone or combined with chlorhexidine, and may be a promising agent for use in oral anti-biofilm strategies in the future.

Amino Acid Enantiomeric Ratios in Biogeochemistry: Complications and Opportunities

Science.gov (United States)

McDonald, G. D.; Sun, H. J.; Tsapin, A. I.

2003-12-01

Amino acid enantiomeric ratios have been used for many years as an indicator of the process of racemization, and thus as a method to determine the age of biological samples such as bones, shells, and teeth. Dating biological samples by this method relies on an accurate knowledge of the environmental temperatures the sample has experienced, and the racemization kinetic parameters in the sample matrix. In some environments, where an independent dating method such as radiocarbon is available, the observed amino acid D/L ratios are found to be either higher or lower than those expected due to racemization alone. The observed D/L ratios in these cases can be clues to biogeochemical processes operating in addition to, or in place of, chemical racemization. In Siberian permafrost (Brinton et al. 2002, Astrobiology 2, 77) we have found D/L ratios lower than expected, which we have interpreted as evidence for low-level D-amino acid metabolism and recycling in microorganisms previously thought to be metabolically dormant. In microbially-colonized Antarctic Dry Valley sandstones (McDonald and Sun 2002, Eos Trans. AGU 83, Fall Meet. Suppl., Abstract B11A-0720) we have found D/L ratios higher than can be accounted for by racemization alone, most likely due to the accumulation of D-amino-acid-containing peptidoglycan material from multiple bacterial generations. D/L profiles in polar ices and in ice-covered lakes (Tsapin et al. 2002, Astrobiology 2, 632) can be used to indicate the sources and histories of water or ice samples. Multiple biological and biogeochemical processes may complicate the interpretation of amino acid enantiomeric excesses in both terrestrial and extraterrestrial samples; however, amino acid racemization remains a useful tool in biogeochemistry and astrobiology. With a good knowledge of the environmental history of samples, amino acid D/L profiles can be used as a window into processes such as molecular repair and biomass turnover that are difficult to

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.

MODEL SCAFFOLDING PEMBELAJARAN MENULIS DENGAN PENDEKATAN PROSES BAGI ANAK TUNARUNGU

Directory of Open Access Journals (Sweden)

Yuliyati Endang Purbaningrum Endang Purbaningrum

2016-10-01

Full Text Available The aim for this researach is (1 to describe the needs analysis and challenges and (2 to produce the scaffolding draft model in learning writing using process ap-proach combined with the reflective maternal method (MMR. This research develop-ment applies R2D2 model which emphasizes users’ need based on the context (teacher-student with difable  and developed collaboratively. Based on the needs analysis in the field in the first year, scaffolding draft model was produced using approach elaborated with the reflective maternal method (MMR.

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.

A new approach to fabrication of Cs/BG/CNT nanocomposite scaffold towards bone tissue engineering and evaluation of its properties

Energy Technology Data Exchange (ETDEWEB)

Shokri, S. [Department of Nanotechnology Engineering, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Movahedi, B., E-mail: b.movahedi@ast.ui.ac.ir [Department of Nanotechnology Engineering, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Rafieinia, M. [Biosensor Research Center, Department of Advanced Medical Technology, Isfahan University of Medical Sciences, Isfahan, 64716 (Iran, Islamic Republic of); Salehi, H. [Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, 64716 (Iran, Islamic Republic of)

2015-12-01

Graphical abstract: - Highlights: • Nanocomposite scaffold was produced using a novel technique. • Bioactive glass, carbon nanotube and chitosan were used for fabrication of nanocomposite scaffold. • The compressive strength of the scaffold was near to the cancellous bone. • Biodegradability of the scaffolds in PBS shows the slow destruction. - Abstract: In the present study, bioactive glass (BG), carbon nanotube (CNT), and chitosan (Cs) were used with different ratios for the fabrication of nanocomposite scaffold for bone tissue engineering. BG was synthesized by sol–gel process and CNT was functionalized by immersing in sulfuric acid as well as nitric acid. Nanocomposite scaffold was produced using a novel technique, hot press, and salt leaching process and cross-linked by Hexamethylene diisocyanate (HDI). The optimum porosity of the scaffold with respect to the ratio of salt and precursor was kept around 70%. Mechanical properties of the scaffolds were increased by the addition of CNT and hence, the compressive strength of them with 4 wt% CNT was increased up to 5.95 ± 0.5 MPa. The nanocomposite scaffolds were characterized by FT-IR, SEM, XRD, and electrochemical analysis. Furthermore, scaffolds were immersed in PBS for evaluating the biodegradability, water absorption, and CNT release. The results indicated that water absorption of the scaffolds was increased by adding CNT to the scaffold. The amount of released CNT after 30 days was measured within 6 × 10{sup −4} and 1 × 10{sup −3} mg/ml. Attachment and proliferation of MG63 osteoblast cell line on Cs/BG/CNT scaffolds were investigated by MTT assay indicating no toxicity for this nanocomposite scaffolds. According to the results of the experiments, the nanocomposite scaffold with modified composition (Cs/BG/CNT, 80:20:2 wt%) was the best one in matters of mechanical, chemical, and cellular properties and also the most appropriate for trabecular bone tissue.

Analogical scaffolding: Making meaning in physics through representation and analogy

Science.gov (United States)

Podolefsky, Noah Solomon

This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

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)

Prokaryotic Selectivity, Anti-endotoxic Activity and Protease Stability of Diastereomeric and Enantiomeric Analogs of Human Antimicrobial Peptide LL-37

International Nuclear Information System (INIS)

Nan, Yong Hai; Lee, Bongju; Shin, Song Yub

2012-01-01

LL-37 is the only antimicrobial peptide (AMP) of the human cathelicidin family. In addition to potent antimicrobial activity, LL-37 is known to have the potential to inhibit lipolysaccharide (LPS)-induced endotoxic effects. To provide the stability to proteolytic digestion and increase prokaryotic selectivity and/or anti-endotoxic activity of two Lys/Trp-substituted 19-meric anti-microbial peptides (a4-W1 and a4-W2) designed from IG-19 (residues 13-31 of LL-37), we synthesized the diastereomeric peptides (a4-W1-D and a4-W2-D) with D-amino acid substitution at positions 3, 7, 10, 13 and 17 of a4-W1 and a4-W2, respectively and the enantiomeric peptides (a4-W1-E and a4-W2-E) composed D-amino acids. The diastereomeric peptides exhibited the best prokaryotic selectivity and effective protease stability, but no or less anti-endotoxic activity. In contrast, the enantiomeric peptides had not only prokaryotic selectivity and anti-endotoxic activity but also protease stability. Our results suggest that the hydrophobicity and α-helicity of the peptide is important for anti-endotoxic activity. In particular, the enantiomeric peptides showed potent anti-endotoxic and LPS-neutralizing activities comparable to that of LL-37. Taken together, both a4-W1-E and a4-W2-E holds promise as a template for the development of peptide antibiotics for the treatment of endotoxic shock and sepsis

Prokaryotic Selectivity, Anti-endotoxic Activity and Protease Stability of Diastereomeric and Enantiomeric Analogs of Human Antimicrobial Peptide LL-37

Energy Technology Data Exchange (ETDEWEB)

Nan, Yong Hai; Lee, Bongju; Shin, Song Yub [Chosun Univ., Gwangju (Korea, Republic of)

2012-09-15

LL-37 is the only antimicrobial peptide (AMP) of the human cathelicidin family. In addition to potent antimicrobial activity, LL-37 is known to have the potential to inhibit lipolysaccharide (LPS)-induced endotoxic effects. To provide the stability to proteolytic digestion and increase prokaryotic selectivity and/or anti-endotoxic activity of two Lys/Trp-substituted 19-meric anti-microbial peptides (a4-W1 and a4-W2) designed from IG-19 (residues 13-31 of LL-37), we synthesized the diastereomeric peptides (a4-W1-D and a4-W2-D) with D-amino acid substitution at positions 3, 7, 10, 13 and 17 of a4-W1 and a4-W2, respectively and the enantiomeric peptides (a4-W1-E and a4-W2-E) composed D-amino acids. The diastereomeric peptides exhibited the best prokaryotic selectivity and effective protease stability, but no or less anti-endotoxic activity. In contrast, the enantiomeric peptides had not only prokaryotic selectivity and anti-endotoxic activity but also protease stability. Our results suggest that the hydrophobicity and α-helicity of the peptide is important for anti-endotoxic activity. In particular, the enantiomeric peptides showed potent anti-endotoxic and LPS-neutralizing activities comparable to that of LL-37. Taken together, both a4-W1-E and a4-W2-E holds promise as a template for the development of peptide antibiotics for the treatment of endotoxic shock and sepsis.

3D printed porous ceramic scaffolds for bone tissue engineering: a review.

Science.gov (United States)

Wen, Yu; Xun, Sun; Haoye, Meng; Baichuan, Sun; Peng, Chen; Xuejian, Liu; Kaihong, Zhang; Xuan, Yang; Jiang, Peng; Shibi, Lu

2017-08-22

This study summarizes the recent research status and development of three-dimensional (3D)-printed porous ceramic scaffolds in bone tissue engineering. Recent literature on 3D-printed porous ceramic scaffolds was reviewed. Compared with traditional processing and manufacturing technologies, 3D-printed porous ceramic scaffolds have obvious advantages, such as enhancement of the controllability of the structure or improvement of the production efficiency. More sophisticated scaffolds were fabricated by 3D printing technology. 3D printed bioceramics have broad application prospects in bone tissue engineering. Through understanding the advantages and limitations of different 3D-printing approaches, new classes of bone graft substitutes can be developed.

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

Improved resolution of 3D printed scaffolds by shrinking.

Science.gov (United States)

Chia, Helena N; Wu, Benjamin M

2015-10-01

Three-dimensional printing (3DP) uses inkjet printheads to selectively deposit liquid binder to adjoin powder particles in a layer-by-layer fashion to create a computer-modeled 3D object. Two general approaches for 3DP have been described for biomedical applications (direct and indirect 3DP). The two approaches offer competing advantages, and both are limited by print resolution. This study describes a materials processing strategy to enhance 3DP resolution by controlled shrinking net-shape scaffolds. Briefly, porogen preforms are printed and infused with the desired monomer or polymer solution. After solidification or polymerization, the porogen is leached and the polymer is allowed to shrink by controlled drying. Heat treatment is performed to retain the dimensions against swelling forces. The main objective of this study is to determine the effects of polymer content and post-processing on dimension, microstructure, and thermomechanical properties of the scaffold. For polyethylene glycol diacrylate (PEG-DA), reducing polymer content corresponded with greater shrinkage with maximum shrinkage of ∼80 vol% at 20% vol% PEG-DA. The secondary heat treatment retains the microarchitecture and new dimensions of the scaffolds, even when the heat-treated scaffolds are immersed into water. To demonstrate shrinkage predictability, 3D components with interlocking positive and negative features were printed, processed, and fitted. This material processing strategy provides an alternative method to enhance the resolution of 3D scaffolds, for a wide range of polymers, without optimizing the binder-powder interaction physics to print each material combination. © 2014 Wiley Periodicals, Inc.

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.

Predicting permeability of regular tissue engineering scaffolds: scaling analysis of pore architecture, scaffold length, and fluid flow rate effects.

Science.gov (United States)

Rahbari, A; Montazerian, H; Davoodi, E; Homayoonfar, S

2017-02-01

The main aim of this research is to numerically obtain the permeability coefficient in the cylindrical scaffolds. For this purpose, a mathematical analysis was performed to derive an equation for desired porosity in terms of morphological parameters. Then, the considered cylindrical geometries were modeled and the permeability coefficient was calculated according to the velocity and pressure drop values based on the Darcy's law. In order to validate the accuracy of the present numerical solution, the obtained permeability coefficient was compared with the published experimental data. It was observed that this model can predict permeability with the utmost accuracy. Then, the effect of geometrical parameters including porosity, scaffold pore structure, unit cell size, and length of the scaffolds as well as entrance mass flow rate on the permeability of porous structures was studied. Furthermore, a parametric study with scaling laws analysis of sample length and mass flow rate effects on the permeability showed good fit to the obtained data. It can be concluded that the sensitivity of permeability is more noticeable at higher porosities. The present approach can be used to characterize and optimize the scaffold microstructure due to the necessity of cell growth and transferring considerations.

Characterization of Electrospun Nanofibrous Scaffolds for Nanobiomedical Applications

Science.gov (United States)

Emul, E.; Saglam, S.; Ates, H.; Korkusuz, F.; Saglam, N.

2016-08-01

The electrospinning method is employed in the production of porous fiber scaffolds, and the usage of electrospun scaffolds especially as drug carrier and bone reconstructive material such as implants is promising for future applications in tissue engineering. The number of publications has grown very rapidly in this field through the fabrication of complex scaffolds, novel approaches in nanotechnology, and improvements of imaging methods. Hence, characterization of these materials has also grown significantly important for getting satisfied and accurate results. This advantageous and versatile method is ideal for mimicking bone extracellular matrix, and many biodegradable and biocompatible polymers are preferred in the field of bone reconstruction. In this study, gelatin, gelatin/nanohydroxyapatite (nHAp) and gelatin/PLLA/nHAp scaffolds were fabricated by the electrospinning process. These composite fibers showed clear and continuous morphology according to observation through a scanning electron microscope and their component analyses were also determined by Fourier transform infrared spectrometer analyses. These characterization experiments revealed the great effects of the electrospinning method for biomedical applications and have an especially important role in bone reconstruction and production of implant coating material.

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)

Alveolar bone tissue engineering using composite scaffolds for drug delivery

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Tomonori Matsuno

2010-08-01

Full Text Available For many years, bone graft substitutes have been used to reconstruct bone defects in orthopedic and dental fields. However, synthetic bone substitutes such as hydroxyapatite or β-tricalcium phosphate have no osteoinductive or osteogenic abilities. Bone tissue engineering has also been promoted as an alternative approach to regenerating bone tissue. To succeed in bone tissue engineering, osteoconductive scaffolding biomaterials should provide a suitable environment for osteogenic cells and provide local controlled release of osteogenic growth factors. In addition, the scaffold for the bone graft substitute should biodegrade to replace the newly formed bone. Recent advances in bone tissue engineering have allowed the creation of composite scaffolds with tailored functional properties. This review focuses on composite scaffolds that consist of synthetic ceramics and natural polymers as drug delivery carriers for alveolar bone tissue engineering.

Platelet lysate 3D scaffold supports mesenchymal stem cell chondrogenesis: an improved approach in cartilage tissue engineering.

Science.gov (United States)

Moroz, Andrei; Bittencourt, Renata Aparecida Camargo; Almeida, Renan Padron; Felisbino, Sérgio Luis; Deffune, Elenice

2013-01-01

Articular lesions are still a major challenge in orthopedics because of cartilage's poor healing properties. A major improvement in therapeutics was the development of autologous chondrocytes implantation (ACI), a biotechnology-derived technique that delivers healthy autologous chondrocytes after in vitro expansion. To obtain cartilage-like tissue, 3D scaffolds are essential to maintain chondrocyte differentiated status. Currently, bioactive 3D scaffolds are promising as they can deliver growth factors, cytokines, and hormones to the cells, giving them a boost to attach, proliferate, induce protein synthesis, and differentiate. Using mesenchymal stem cells (MSCs) differentiated into chondrocytes, one can avoid cartilage harvesting. Thus, we investigated the potential use of a platelet-lysate-based 3D bioactive scaffold to support chondrogenic differentiation and maintenance of MSCs. The MSCs from adult rabbit bone marrow (n = 5) were cultivated and characterized using three antibodies by flow cytometry. MSCs (1 × 10(5)) were than encapsulated inside 60 µl of a rabbit platelet-lysate clot scaffold and maintained in Dulbecco's Modified Eagle Medium Nutrient Mixture F-12 supplemented with chondrogenic inductors. After 21 days, the MSCs-seeded scaffolds were processed for histological analysis and stained with toluidine blue. This scaffold was able to maintain round-shaped cells, typical chondrocyte metachromatic extracellular matrix deposition, and isogenous group formation. Cells accumulated inside lacunae and cytoplasm lipid droplets were other observed typical chondrocyte features. In conclusion, the usage of a platelet-lysate bioactive scaffold, associated with a suitable chondrogenic culture medium, supports MSCs chondrogenesis. As such, it offers an alternative tool for cartilage engineering research and ACI.

In Vitro Testing of Scaffolds for Mesenchymal Stem Cell-Based Meniscus Tissue Engineering—Introducing a New Biocompatibility Scoring System

Directory of Open Access Journals (Sweden)

Felix P. Achatz

2016-04-01

Full Text Available A combination of mesenchymal stem cells (MSCs and scaffolds seems to be a promising approach for meniscus repair. To facilitate the search for an appropriate scaffold material a reliable and objective in vitro testing system is essential. This paper introduces a new scoring for this purpose and analyzes a hyaluronic acid (HA gelatin composite scaffold and a polyurethane scaffold in combination with MSCs for tissue engineering of meniscus. The pore quality and interconnectivity of pores of a HA gelatin composite scaffold and a polyurethane scaffold were analyzed by surface photography and Berliner-Blau-BSA-solution vacuum filling. Further the two scaffold materials were vacuum-filled with human MSCs and analyzed by histology and immunohistochemistry after 21 days in chondrogenic media to determine cell distribution and cell survival as well as proteoglycan production, collagen type I and II content. The polyurethane scaffold showed better results than the hyaluronic acid gelatin composite scaffold, with signs of central necrosis in the HA gelatin composite scaffolds. The polyurethane scaffold showed good porosity, excellent pore interconnectivity, good cell distribution and cell survival, as well as an extensive content of proteoglycans and collagen type II. The polyurethane scaffold seems to be a promising biomaterial for a mesenchymal stem cell-based tissue engineering approach for meniscal repair. The new score could be applied as a new standard for in vitro scaffold testing.

Scaffolding in Business English Correspondence Classes at College Level

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Eric Sulindra Widjojokoesoemo

2015-11-01

Full Text Available Language teaching and education have been so long influenced by developmental psychology, namely constructivism. This idea enlightens the world of language teaching. Constructivism has received both praises and critics. Communicative approach followers claim that the principles in constructivism support their thoughts while the followers of a more traditional approach, namely, Grammar Translation Method, claim that the constructivism is just another experiment in language teaching, just like other methods. This article is based on a classroom action research investigation of how scaffolding instruction, the operational ‘terms’ of constructivism, based on its ‘ZPD’ (Zone of Proximal Development, play roles in language teaching, specifically in Business English Writing. The investigation has perceived several important aspects in scaffolding instruction for teaching Business English Correspondence, such as the importance of modeling or giving examples, as well as corrective and immediate feedback, together with positive reinforcement, to improve the learners’ performance. It showed that modeling or giving examples, peer reviewing, together with immediate feedback, brought significant influence on the learners’ perspective, about their learning performance. Keywords: constructivism, Scaffolding, ZPD, Business English Writing

Cardiomyocyte behavior on biodegradable polyurethane/gold nanocomposite scaffolds under electrical stimulation

Energy Technology Data Exchange (ETDEWEB)

Ganji, Yasaman [Faculty of Biomedical Engineering, Amirkabir University of Technology, 424 Hafez Ave, Tehran (Iran, Islamic Republic of); Institute for Materials Science, Dept. Biocompatible Nanomaterials, University of Kiel, Kaiserstr. 2, D-24143 Kiel (Germany); Li, Qian [Institute for Materials Science, Dept. Biocompatible Nanomaterials, University of Kiel, Kaiserstr. 2, D-24143 Kiel (Germany); Quabius, Elgar Susanne [Dept. of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Arnold-Heller-Str. 3, Building 27, D-24105 Kiel (Germany); Institute of Immunology, University of Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel (Germany); Böttner, Martina [Department of Anatomy, University of Kiel, Otto-Hahn-Platz 8, 24118 Kiel (Germany); Selhuber-Unkel, Christine, E-mail: cse@tf.uni-kiel.de [Institute for Materials Science, Dept. Biocompatible Nanomaterials, University of Kiel, Kaiserstr. 2, D-24143 Kiel (Germany); Kasra, Mehran [Faculty of Biomedical Engineering, Amirkabir University of Technology, 424 Hafez Ave, Tehran (Iran, Islamic Republic of)

2016-02-01

Following a myocardial infarction (MI), cardiomyocytes are replaced by scar tissue, which decreases ventricular contractile function. Tissue engineering is a promising approach to regenerate such damaged cardiomyocyte tissue. Engineered cardiac patches can be fabricated by seeding a high density of cardiac cells onto a synthetic or natural porous polymer. In this study, nanocomposite scaffolds made of gold nanotubes/nanowires incorporated into biodegradable castor oil-based polyurethane were employed to make micro-porous scaffolds. H9C2 cardiomyocyte cells were cultured on the scaffolds for one day, and electrical stimulation was applied to improve cell communication and interaction in neighboring pores. Cells on scaffolds were examined by fluorescence microscopy and scanning electron microscopy, revealing that the combination of scaffold design and electrical stimulation significantly increased cell confluency of H9C2 cells on the scaffolds. Furthermore, we showed that the gene expression levels of Nkx2.5, atrial natriuretic peptide (ANF) and natriuretic peptide precursor B (NPPB), which are functional genes of the myocardium, were up-regulated by the incorporation of gold nanotubes/nanowires into the polyurethane scaffolds, in particular after electrical stimulation. - Highlights: • Biodegradable polyurethane/gold nanocomposites for cardiomyocyte adhesion are proposed. • The nanocomposite scaffolds are porous and electrical stimulation enhances cell adhesion. • Expression levels of functional myocardium genes were upregulated after electrical stimulation.

Structural determinants of hydration, mechanics and fluid flow in freeze-dried collagen scaffolds.

Science.gov (United States)

Offeddu, G S; Ashworth, J C; Cameron, R E; Oyen, M L

2016-09-01

Freeze-dried scaffolds provide regeneration templates for a wide range of tissues, due to their flexibility in physical and biological properties. Control of structure is crucial for tuning such properties, and therefore scaffold functionality. However, the common approach of modeling these scaffolds as open-cell foams does not fully account for their structural complexity. Here, the validity of the open-cell model is examined across a range of physical characteristics, rigorously linking morphology to hydration and mechanical properties. Collagen scaffolds with systematic changes in relative density were characterized using Scanning Electron Microscopy, X-ray Micro-Computed Tomography and spherical indentation analyzed in a time-dependent poroelastic framework. Morphologically, all scaffolds were mid-way between the open- and closed-cell models, approaching the closed-cell model as relative density increased. Although pore size remained constant, transport pathway diameter decreased. Larger collagen fractions also produced greater volume swelling on hydration, although the change in pore diameter was constant, and relatively small at ∼6%. Mechanically, the dry and hydrated scaffold moduli varied quadratically with relative density, as expected of open-cell materials. However, the increasing pore wall closure was found to determine the time-dependent nature of the hydrated scaffold response, with a decrease in permeability producing increasingly elastic rather than viscoelastic behavior. These results demonstrate that characterizing the deviation from the open-cell model is vital to gain a full understanding of scaffold biophysical properties, and provide a template for structural studies of other freeze-dried biomaterials. Freeze-dried collagen sponges are three-dimensional microporous scaffolds that have been used for a number of exploratory tissue engineering applications. The characterization of the structure-properties relationships of these scaffolds is

Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

Science.gov (United States)

Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

2015-07-01

The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. © 2014 Wiley Periodicals, Inc.

Antimicrobial 3D Porous Scaffolds Prepared by Additive Manufacturing and Breath Figures.

Science.gov (United States)

Vargas-Alfredo, Nelson; Dorronsoro, Ane; Cortajarena, Aitziber L; Rodríguez-Hernández, Juan

2017-10-25

We describe herein a novel strategy for the fabrication of efficient 3D printed antibacterial scaffolds. For this purpose, both the surface topography as well as the chemical composition of 3D scaffolds fabricated by additive manufacturing were modified. The scaffolds were fabricated by fused deposition modeling (FDM) using high-impact polystyrene (HIPS) filaments. The surface of the objects was then topographically modified providing materials with porous surfaces by means of the Breath Figures approach. The strategy involves the immersion of the scaffold in a polymer solution during a precise period of time. This approach permitted the modification of the pore size varying the immersion time as well as the solution concentration. Moreover, by using polymer blend solutions of polystyrene and polystyrene-b-poly(acrylic acid) (PS 23 -b-PAA 18 ) and a quaternized polystyrene-b-poly(dimethylaminoethyl methacrylate) (PS 42 -b-PDMAEMAQ 17 ), the scaffolds were simultaneously chemically modified. The surfaces were characterized by scanning electron microscopy and infrared spectroscopy. Finally, the biological response toward bacteria was explored. Porous surfaces prepared using quaternized PDMAEMA as well as those prepared using PAA confer antimicrobial activity to the films, i.e., were able to kill on contact Staphylococcus aureus employed as model bacteria.

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.

Continuous cellularization of calcium phosphate hybrid scaffolds induced by plasma polymer activation

Energy Technology Data Exchange (ETDEWEB)

Bergemann, Claudia [University Medical Center Rostock, Cell Biology, Schillingallee 69, D-18057 Rostock (Germany); Cornelsen, Matthias [University of Rostock, Fluid Technology and Microfluidics, Justus-von-Liebig Weg 6, D-18059 Rostock (Germany); Quade, Antje [Leibniz-Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, D-17489 Greifswald (Germany); Laube, Thorsten; Schnabelrauch, Matthias [INNOVENT e.V., Biomaterials Department, Pruessingstrasse 27B, D-07745 Jena (Germany); Rebl, Henrike [University Medical Center Rostock, Cell Biology, Schillingallee 69, D-18057 Rostock (Germany); Weißmann, Volker [Institute for Polymer Technologies (IPT) e.V., Alter Holzhafen 19, D-23966 Wismar (Germany); Seitz, Hermann [University of Rostock, Fluid Technology and Microfluidics, Justus-von-Liebig Weg 6, D-18059 Rostock (Germany); Nebe, Barbara, E-mail: barbara.nebe@med.uni-rostock.de [University Medical Center Rostock, Cell Biology, Schillingallee 69, D-18057 Rostock (Germany)

2016-02-01

The generation of hybrid materials based on β-tricalcium phosphate (TCP) and various biodegradable polymers like poly(L-lactide-co-D,L-lactide) (PLA) represents a common approach to overcoming the disadvantages of pure TCP devices. These disadvantages lie in TCP's mechanical properties, such as brittleness. The positive characteristic of PLA — improvement of compressive strength of calcium phosphate scaffolds – is diametrically opposed to its cell attractiveness. Therefore, the objective of this work was to optimize osteoblast migration and cellularization inside a three-dimensionally (3D) printed, PLA polymer stabilized TCP hybrid scaffold by a plasma polymer process depositing amino groups via allylamine. MG-63 osteoblastic cells inside the 10 mm hybrid scaffold were dynamically cultivated for 14 days in a 3D model system integrated in a perfusion reactor. The whole TCP/PLA hybrid scaffold was continuously colonized due to plasma polymerized allylamine activation inducing the migration potential of osteoblasts. - Highlights: • Mechanical stabilization of β-tricalcium phosphate scaffolds by PLA infiltration • Hybrid scaffolds with higher cell attraction due to plasma polymerized allylamine • 3D perfusion in vitro model for observation of cell migration inside scaffolds • Enhanced cell migration within plasma polymer coated TCP hybrid scaffolds.

Continuous cellularization of calcium phosphate hybrid scaffolds induced by plasma polymer activation

International Nuclear Information System (INIS)

Bergemann, Claudia; Cornelsen, Matthias; Quade, Antje; Laube, Thorsten; Schnabelrauch, Matthias; Rebl, Henrike; Weißmann, Volker; Seitz, Hermann; Nebe, Barbara

2016-01-01

The generation of hybrid materials based on β-tricalcium phosphate (TCP) and various biodegradable polymers like poly(L-lactide-co-D,L-lactide) (PLA) represents a common approach to overcoming the disadvantages of pure TCP devices. These disadvantages lie in TCP's mechanical properties, such as brittleness. The positive characteristic of PLA — improvement of compressive strength of calcium phosphate scaffolds – is diametrically opposed to its cell attractiveness. Therefore, the objective of this work was to optimize osteoblast migration and cellularization inside a three-dimensionally (3D) printed, PLA polymer stabilized TCP hybrid scaffold by a plasma polymer process depositing amino groups via allylamine. MG-63 osteoblastic cells inside the 10 mm hybrid scaffold were dynamically cultivated for 14 days in a 3D model system integrated in a perfusion reactor. The whole TCP/PLA hybrid scaffold was continuously colonized due to plasma polymerized allylamine activation inducing the migration potential of osteoblasts. - Highlights: • Mechanical stabilization of β-tricalcium phosphate scaffolds by PLA infiltration • Hybrid scaffolds with higher cell attraction due to plasma polymerized allylamine • 3D perfusion in vitro model for observation of cell migration inside scaffolds • Enhanced cell migration within plasma polymer coated TCP hybrid scaffolds

Occurrence of organochlorine pesticides (OCPs) and their enantiomeric signatures, and concentrations of polybrominated diphenyl ethers (PBDEs) in the Adelie penguin food web, Antarctica

International Nuclear Information System (INIS)

Corsolini, Simonetta; Covaci, Adrian; Ademollo, Nicoletta; Focardi, Silvano; Schepens, Paul

2006-01-01

Concentrations and enantiomeric signatures of organochlorine pesticides were determined in Antarctic krill, emerald rockcod and Adelie penguin from the Ross Sea, Antarctica. HCB and DDTs were prevalent contaminants in penguin eggs. The highest concentrations of ΣHCHs (1.35 ± 0.72 ng/g) were found in the rockcod muscle, where γ-HCH (1.23 ± 0.67 ng/g) was the principal isomer. The ratio γ-HCH/α-HCH was evaluated. Enantioselective gas chromatography was used for the evaluation of enantiomeric fractions (EFs) for α-HCH and oxychlordane. An increase of 14% in the (+)α-HCH enantiomer was found from krill through penguin, suggesting the enantioselective biotrasformation increased proportionately with trophic level. Polybrominated diphenyl ethers (PBDEs) were measured and their concentrations were 5.6 ± 1.12, 5.81 ± 2.32, 4.57 ± 0.17 and 3.06 ± 3.27 ng/g lipids in krill, rockcod muscle, rockcod homogenate and penguin eggs, respectively. The detection of BDE28, BDE47, BDE99 and BDE100 in Antarctic organisms confirmed their global transport and distribution; the detection of lower brominated congeners suggested a potential long-range transport. - Enantiomeric signature and accumulation of polybrominated diphenyl ethers in the Adelie Penguin food chain are discussed

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

Science.gov (United States)

Chaudhari, Atul A; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R

2016-11-25

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Biomimetic apatite-coated porous PVA scaffolds promote the growth of breast cancer cells

International Nuclear Information System (INIS)

Ye, Mao; Mohanty, Pravansu; Ghosh, Gargi

2014-01-01

Recapitulating the native environment of bone tissue is essential to develop in vitro models of breast cancer bone metastasis. The bone is a composite material consisting of organic matrix and inorganic mineral phase, primarily hydroxyapatite. In this study, we report the mineralization of porous poly vinyl alcohol (PVA) scaffolds upon incubation in modified Hanks' Balanced Salt Solution (HBSS) for 14 days. Scanning electron microscopy, energy dispersive X-ray analysis, and X-ray diffraction analysis revealed that the deposited minerals have composition similar to hydroxyapatite. The study demonstrated that the rate of nucleation and growth of minerals was faster on surfaces of less porous scaffolds. However, upon prolonged incubation, formation of mineral layer was observed on the surface of all the scaffolds. In addition, the study also demonstrated that 3D mineralization only occurred for scaffolds with highly interconnected porous networks. The mineralization of the scaffolds promoted the adsorption of serum proteins and consequently, the adhesion and proliferation of breast cancer cells. - Highlights: • Porous PVA scaffolds fabricated via mechanical agitation followed by freeze-drying. • Mineralization of the scaffold was carried out by utilizing biomimetic approach. • Mineralization resulted in increased protein adsorption on the scaffold. • Increased breast cancer cell growth was observed on mineralized scaffolds

Biomimetic apatite-coated porous PVA scaffolds promote the growth of breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Ye, Mao; Mohanty, Pravansu; Ghosh, Gargi, E-mail: gargi@umich.edu

2014-11-01

Recapitulating the native environment of bone tissue is essential to develop in vitro models of breast cancer bone metastasis. The bone is a composite material consisting of organic matrix and inorganic mineral phase, primarily hydroxyapatite. In this study, we report the mineralization of porous poly vinyl alcohol (PVA) scaffolds upon incubation in modified Hanks' Balanced Salt Solution (HBSS) for 14 days. Scanning electron microscopy, energy dispersive X-ray analysis, and X-ray diffraction analysis revealed that the deposited minerals have composition similar to hydroxyapatite. The study demonstrated that the rate of nucleation and growth of minerals was faster on surfaces of less porous scaffolds. However, upon prolonged incubation, formation of mineral layer was observed on the surface of all the scaffolds. In addition, the study also demonstrated that 3D mineralization only occurred for scaffolds with highly interconnected porous networks. The mineralization of the scaffolds promoted the adsorption of serum proteins and consequently, the adhesion and proliferation of breast cancer cells. - Highlights: • Porous PVA scaffolds fabricated via mechanical agitation followed by freeze-drying. • Mineralization of the scaffold was carried out by utilizing biomimetic approach. • Mineralization resulted in increased protein adsorption on the scaffold. • Increased breast cancer cell growth was observed on mineralized scaffolds.

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

Magnesium interference and different efficiencies of diastereoisomeric cluster formation in phenylalanine enantiomeric discrimination by the kinetic method

Czech Academy of Sciences Publication Activity Database

Ranc, V.; Havlíček, Vladimír; Bednář, P.; Lemr, Karel

2009-01-01

Roč. 280, 1-3 (2009), s. 213-217 ISSN 1387-3806 R&D Projects: GA MŠk LC07017; GA ČR GA203/07/0765 Grant - others:XE(XE) EC: MKTD-CT-2004-014407 Institutional research plan: CEZ:AV0Z50200510 Keywords : enantiomeric dicrimination * kinetic method * mass spectrometry Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.117, year: 2009

In Vivo Evaluation of Biocompatibility and Chondrogenic Potential of a Cell-Free Collagen-Based Scaffold

Directory of Open Access Journals (Sweden)

Giovanna Calabrese

2017-11-01

Full Text Available Injured articular cartilage has a limited innate regenerative capacity, due to the avascular nature and low cellularity of the tissue itself. Although several approaches have been proposed to repair the joint cartilage, none of them has proven to be effective. The absence of suitable therapeutic options has encouraged tissue-engineering approaches combining specific cell types and biomaterials. In the present work, we have evaluated the potential of a cell-free Collagen I-based scaffold to promote the augmentation of cartilage-like phenotype after subcutaneous implantation in the mouse. Forty female mice were grafted subcutaneously with scaffolds, while four additional mice without scaffold were used as negative controls. The effects of scaffold were evaluated at 1, 2, 4, 8, or 16 weeks after implantation. Immunohistochemical analysis shows the expression of typical cartilage markers, including type-II Collagen, Aggrecan, Matrilin-1 and Sox 9. These data are also confirmed by qRT-PCR that further show that both COL2A1 and COL1A1 increase over time, but the first one increases more rapidly, thus suggesting a typical cartilage-like address. Histological analysis shows the presence of some pericellular lacunae, after 8 and 16 weeks. Results suggest that this scaffold (i is biocompatible in vivo, (ii is able to recruit host cells (iii induce chondrogenic differentiation of host cells. Such evidences suggest that this cell-free scaffold is promising and represents a potential approach for cartilage regeneration.

Novel fiber-based pure chitosan scaffold for tendon augmentation: biomechanical and cell biological evaluation.

Science.gov (United States)

Nowotny, J; Aibibu, D; Farack, J; Nimtschke, U; Hild, M; Gelinsky, M; Kasten, P; Cherif, Ch

2016-07-01

One possibility to improve the mechanical properties after tendon ruptures is augmentation with a scaffold. Based on wet spinning technology, chitosan fibres were processed to a novel pure high-grade multifilament yarn with reproducible quality. The fibres were braided to obtain a 3D tendon scaffold. The CS fibres and scaffolds were evaluated biomechanically and compared to human supraspinatus (SSP) tendons. For the cytobiological characterization, in vitro cell culture experiments with human mesenchymal stem cells (hMSC) were performed. Three types of 3D circular braided scaffolds were fabricated. Significantly, higher ultimate stress values were measured for scaffold with larger filament yarn, compared to scaffold with smaller filament yarn. During cultivation over 28 days, the cells showed in dependence of isolation method and/or donor a doubling or tripling of the cell number or even a six-fold increase on the CS scaffold, which was comparable to the control (polystyrene) or in the case of cells obtained from human biceps tendon even higher proliferation rates. After 14 days, the scaffold surface was covered homogeneously with a cell layer. In summary, the present work demonstrates that braided chitosan scaffolds constitute a straightforward approach for designing tendon analogues, maintaining important flexibility in scaffold design and providing favourable mechanical properties of the resulting construct.

Bone tissue engineering with a collagen–hydroxyapatite scaffold and culture expanded bone marrow stromal cells

Science.gov (United States)

Villa, Max M.; Wang, Liping; Huang, Jianping; Rowe, David W.; Wei, Mei

2015-01-01

Osteoprogenitor cells combined with supportive biomaterials represent a promising approach to advance the standard of care for bone grafting procedures. However, this approach faces challenges, including inconsistent bone formation, cell survival in the implant, and appropriate biomaterial degradation. We have developed a collagen–hydroxyapatite (HA) scaffold that supports consistent osteogenesis by donor derived osteoprogenitors, and is more easily degraded than a pure ceramic scaffold. Herein, the material properties are characterized as well as cell attachment, viability, and progenitor distribution in vitro. Furthermore, we examined the biological performance in vivo in a critical-size mouse calvarial defect. To aid in the evaluation of the in-house collagen–HA scaffold, the in vivo performance was compared with a commercial collagen–HA scaffold (Healos®, Depuy). The in-house collagen–HA scaffold supported consistent bone formation by predominantly donor-derived osteoblasts, nearly completely filling a 3.5 mm calvarial defect with bone in all samples (n=5) after 3 weeks of implantation. In terms of bone formation and donor cell retention at 3 weeks postimplantation, no statistical difference was found between the in-house and commercial scaffold following quantitative histomorphometry. The collagen–HA scaffold presented here is an open and well-defined platform that supports robust bone formation and should facilitate the further development of collagen–hydroxyapatite biomaterials for bone tissue engineering. PMID:24909953

Enantioselective degradation and enantiomerization of indoxacarb in soil.

Science.gov (United States)

Sun, Dali; Pang, Junxiao; Qiu, Jing; Li, Li; Liu, Chenglan; Jiao, Bining

2013-11-27

In this study, the enantioselective degradation and enantiomerizaton of indoxacarb were investigated in two soils under nonsterilized and sterilized conditions using a chiral OD-RH column on a reversed-phase HPLC. Under nonsterilized conditions, the degradation of indoxacarb in two soils was enantioselective. In acidic soil, the half-lives of R-(-)- and S-(+)-indoxacarb were 10.43 and 14.00 days, respectively. Acidic soil was preferential to the degradation of R-(-)-indoxacarb. In alkaline soil, the half-lives of R-(-)- and S-(+)-indoxacarb were 12.14 and 4.88 days, respectively. S-(+)-Indoxacarb was preferentially degraded. Under sterilized conditions, approximately 5-10% of the initial concentration degraded after 75 days of incubation in acidic soil, whereas in alkaline soil, approximately half of the initial concentration degraded due to chemical hydrolysis under alkaline conditions. Enantiomerization was also discovered in acidic and alkaline soils. The results showed that mutual transformation existed between two enantiomers and that S-(+)-indoxacarb had a significantly higher inversion rate to R-(-)-indoxacarb than its antipode.

Extracellular matrix scaffolds for cartilage and bone regeneration

NARCIS (Netherlands)

Benders, K.E.M.; van Weeren, P.R.; Badylak, S.F.; Saris, Daniël B.F.; Dhert, W.J.A.; Malda, J.

2013-01-01

Regenerative medicine approaches based on decellularized extracellular matrix (ECM) scaffolds and tissues are rapidly expanding. The rationale for using ECM as a natural biomaterial is the presence of bioactive molecules that drive tissue homeostasis and regeneration. Moreover, appropriately

Bioactive glass-reinforced bioceramic ink writing scaffolds: sintering, microstructure and mechanical behavior.

Science.gov (United States)

Shao, Huifeng; Yang, Xianyan; He, Yong; Fu, Jianzhong; Liu, Limin; Ma, Liang; Zhang, Lei; Yang, Guojing; Gao, Changyou; Gou, Zhongru

2015-09-10

The densification of pore struts in bioceramic scaffolds is important for structure stability and strength reliability. An advantage of ceramic ink writing is the precise control over the microstructure and macroarchitecture. However, the use of organic binder in such ink writing process would heavily affect the densification of ceramic struts and sacrifice the mechanical strength of porous scaffolds after sintering. This study presents a low-melt-point bioactive glass (BG)-assisted sintering strategy to overcome the main limitations of direct ink writing (extrusion-based three-dimensional printing) and to produce high-strength calcium silicate (CSi) bioceramic scaffolds. The 1% BG-added CSi (CSi-BG1) scaffolds with rectangular pore morphology sintered at 1080 °C have a very small BG content, readily induce apatite formation, and show appreciable linear shrinkage (∼21%), which is consistent with the composite scaffolds with less or more BG contents sintered at either the same or a higher temperature. These CSi-BG1 scaffolds also possess a high elastic modulus (∼350 MPa) and appreciable compressive strength (∼48 MPa), and show significant strength enhancement after exposure to simulated body fluid-a performance markedly superior to those of pure CSi scaffolds. Particularly, the honeycomb-pore CSi-BG1 scaffolds show markedly higher compressive strength (∼88 MPa) than the scaffolds with rectangular, parallelogram, and Archimedean chord pore structures. It is suggested that this approach can potentially facilitate the translation of ceramic ink writing and BG-assisted sintering of bioceramic scaffold technologies to the in situ bone repair.

Development and Characterization of Organic Electronic Scaffolds for Bone Tissue Engineering.

Science.gov (United States)

Iandolo, Donata; Ravichandran, Akhilandeshwari; Liu, Xianjie; Wen, Feng; Chan, Jerry K Y; Berggren, Magnus; Teoh, Swee-Hin; Simon, Daniel T

2016-06-01

Bones have been shown to exhibit piezoelectric properties, generating electrical potential upon mechanical deformation and responding to electrical stimulation with the generation of mechanical stress. Thus, the effects of electrical stimulation on bone tissue engineering have been extensively studied. However, in bone regeneration applications, only few studies have focused on the use of electroactive 3D biodegradable scaffolds at the interphase with stem cells. Here a method is described to combine the bone regeneration capabilities of 3D-printed macroporous medical grade polycaprolactone (PCL) scaffolds with the electrical and electrochemical capabilities of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). PCL scaffolds have been highly effective in vivo as bone regeneration grafts, and PEDOT is a leading material in the field of organic bioelectronics, due to its stability, conformability, and biocompatibility. A protocol is reported for scaffolds functionalization with PEDOT, using vapor-phase polymerization, resulting in a conformal conducting layer. Scaffolds' porosity and mechanical stability, important for in vivo bone regeneration applications, are retained. Human fetal mesenchymal stem cells proliferation is assessed on the functionalized scaffolds, showing the cytocompatibility of the polymeric coating. Altogether, these results show the feasibility of the proposed approach to obtain electroactive scaffolds for electrical stimulation of stem cells for regenerative medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro cytocompatibility evaluation of chitosan/graphene oxide 3D scaffold composites designed for bone tissue engineering.

Science.gov (United States)

Dinescu, Sorina; Ionita, Mariana; Pandele, Andreea Madalina; Galateanu, Bianca; Iovu, Horia; Ardelean, Aurel; Costache, Marieta; Hermenean, Anca

2014-01-01

Extensively studied nowadays, graphene oxide (GO) has a benefic effect on cell proliferation and differentiation, thus holding promise for bone tissue engineering (BTE) approaches. The aim of this study was not only to design a chitosan 3D scaffold improved with GO for optimal BTE, but also to analyze its physicochemical properties and to evaluate its cytocompatibility and ability to support cell metabolic activity and proliferation. Overall results show that the addition of GO in the scaffold's composition improved mechanical properties and pore formation and enhanced the bioactivity of the scaffold material for tissue engineering. The new developed CHT/GO 3 wt% scaffold could be a potential candidate for further in vitro and in vivo osteogenesis studies and BTE approaches.

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.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

Directory of Open Access Journals (Sweden)

Atul A. Chaudhari

2016-11-01

Full Text Available Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL, and poly-ethylene-glycol (PEG, etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Characterization of Mechanical Properties of Tissue Scaffolds by Phase Contrast Imaging and Finite Element Modeling.

Science.gov (United States)

Bawolin, Nahshon K; Dolovich, Allan T; Chen, Daniel X B; Zhang, Chris W J

2015-08-01

In tissue engineering, the cell and scaffold approach has shown promise as a treatment to regenerate diseased and/or damaged tissue. In this treatment, an artificial construct (scaffold) is seeded with cells, which organize and proliferate into new tissue. The scaffold itself biodegrades with time, leaving behind only newly formed tissue. The degradation qualities of the scaffold are critical during the treatment period, since the change in the mechanical properties of the scaffold with time can influence cell behavior. To observe in time the scaffold's mechanical properties, a straightforward method is to deform the scaffold and then characterize scaffold deflection accordingly. However, experimentally observing the scaffold deflection is challenging. This paper presents a novel study on characterization of mechanical properties of scaffolds by phase contrast imaging and finite element modeling, which specifically includes scaffold fabrication, scaffold imaging, image analysis, and finite elements (FEs) modeling of the scaffold mechanical properties. The innovation of the work rests on the use of in-line phase contrast X-ray imaging at 20 KeV to characterize tissue scaffold deformation caused by ultrasound radiation forces and the use of the Fourier transform to identify movement. Once deformation has been determined experimentally, it is then compared with the predictions given by the forward solution of a finite element model. A consideration of the number of separate loading conditions necessary to uniquely identify the material properties of transversely isotropic and fully orthotropic scaffolds is also presented, along with the use of an FE as a form of regularization.

Cartilage Tissue Engineering with Silk Fibroin Scaffolds Fabricated by Indirect Additive Manufacturing Technology.

Science.gov (United States)

Chen, Chih-Hao; Liu, Jolene Mei-Jun; Chua, Chee-Kai; Chou, Siaw-Meng; Shyu, Victor Bong-Hang; Chen, Jyh-Ping

2014-03-13

Advanced tissue engineering (TE) technology based on additive manufacturing (AM) can fabricate scaffolds with a three-dimensional (3D) environment suitable for cartilage regeneration. Specifically, AM technology may allow the incorporation of complex architectural features. The present study involves the fabrication of 3D TE scaffolds by an indirect AM approach using silk fibroin (SF). From scanning electron microscopic observations, the presence of micro-pores and interconnected channels within the scaffold could be verified, resulting in a TE scaffold with both micro- and macro-structural features. The intrinsic properties, such as the chemical structure and thermal characteristics of SF, were preserved after the indirect AM manufacturing process. In vitro cell culture within the SF scaffold using porcine articular chondrocytes showed a steady increase in cell numbers up to Day 14. The specific production (per cell basis) of the cartilage-specific extracellular matrix component (collagen Type II) was enhanced with culture time up to 12 weeks, indicating the re-differentiation of chondrocytes within the scaffold. Subcutaneous implantation of the scaffold-chondrocyte constructs in nude mice also confirmed the formation of ectopic cartilage by histological examination and immunostaining.

Finite element study of scaffold architecture design and culture conditions for tissue engineering.

Science.gov (United States)

Olivares, Andy L; Marsal, Elia; Planell, Josep A; Lacroix, Damien

2009-10-01

Tissue engineering scaffolds provide temporary mechanical support for tissue regeneration and transfer global mechanical load to mechanical stimuli to cells through its architecture. In this study the interactions between scaffold pore morphology, mechanical stimuli developed at the cell microscopic level, and culture conditions applied at the macroscopic scale are studied on two regular scaffold structures. Gyroid and hexagonal scaffolds of 55% and 70% porosity were modeled in a finite element analysis and were submitted to an inlet fluid flow or compressive strain. A mechanoregulation theory based on scaffold shear strain and fluid shear stress was applied for determining the influence of each structures on the mechanical stimuli on initial conditions. Results indicate that the distribution of shear stress induced by fluid perfusion is very dependent on pore distribution within the scaffold. Gyroid architectures provide a better accessibility of the fluid than hexagonal structures. Based on the mechanoregulation theory, the differentiation process in these structures was more sensitive to inlet fluid flow than axial strain of the scaffold. This study provides a computational approach to determine the mechanical stimuli at the cellular level when cells are cultured in a bioreactor and to relate mechanical stimuli with cell differentiation.

Cartilage Tissue Engineering with Silk Fibroin Scaffolds Fabricated by Indirect Additive Manufacturing Technology

Directory of Open Access Journals (Sweden)

Chih-Hao Chen

2014-03-01

Full Text Available Advanced tissue engineering (TE technology based on additive manufacturing (AM can fabricate scaffolds with a three-dimensional (3D environment suitable for cartilage regeneration. Specifically, AM technology may allow the incorporation of complex architectural features. The present study involves the fabrication of 3D TE scaffolds by an indirect AM approach using silk fibroin (SF. From scanning electron microscopic observations, the presence of micro-pores and interconnected channels within the scaffold could be verified, resulting in a TE scaffold with both micro- and macro-structural features. The intrinsic properties, such as the chemical structure and thermal characteristics of SF, were preserved after the indirect AM manufacturing process. In vitro cell culture within the SF scaffold using porcine articular chondrocytes showed a steady increase in cell numbers up to Day 14. The specific production (per cell basis of the cartilage-specific extracellular matrix component (collagen Type II was enhanced with culture time up to 12 weeks, indicating the re-differentiation of chondrocytes within the scaffold. Subcutaneous implantation of the scaffold-chondrocyte constructs in nude mice also confirmed the formation of ectopic cartilage by histological examination and immunostaining.

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.

Three-Dimensional Elastomeric Scaffolds Designed with Cardiac-Mimetic Structural and Mechanical Features

Science.gov (United States)

Neal, Rebekah A.; Jean, Aurélie; Park, Hyoungshin; Wu, Patrick B.; Hsiao, James; Engelmayr, George C.; Langer, Robert

2013-01-01

Tissue-engineered constructs, at the interface of material science, biology, engineering, and medicine, have the capacity to improve outcomes for cardiac patients by providing living cells and degradable biomaterials that can regenerate the native myocardium. With an ultimate goal of both delivering cells and providing mechanical support to the healing heart, we designed three-dimensional (3D) elastomeric scaffolds with (1) stiffnesses and anisotropy mimicking explanted myocardial specimens as predicted by finite-element (FE) modeling, (2) systematically varied combinations of rectangular pore pattern, pore aspect ratio, and strut width, and (3) structural features approaching tissue scale. Based on predicted mechanical properties, three scaffold designs were selected from eight candidates for fabrication from poly(glycerol sebacate) by micromolding from silicon wafers. Large 20×20 mm scaffolds with high aspect ratio features (5:1 strut height:strut width) were reproducibly cast, cured, and demolded at a relatively high throughput. Empirically measured mechanical properties demonstrated that scaffolds were cardiac mimetic and validated FE model predictions. Two-layered scaffolds providing fully interconnected pore networks were fabricated by layer-by-layer assembly. C2C12 myoblasts cultured on one-layered scaffolds exhibited specific patterns of cell elongation and interconnectivity that appeared to be guided by the scaffold pore pattern. Neonatal rat heart cells cultured on two-layered scaffolds for 1 week were contractile, both spontaneously and in response to electrical stimulation, and expressed sarcomeric α-actinin, a cardiac biomarker. This work not only demonstrated several scaffold designs that promoted functional assembly of rat heart cells, but also provided the foundation for further computational and empirical investigations of 3D elastomeric scaffolds for cardiac tissue engineering. PMID:23190320

Reducing the concentration to 0.4% enantiomeric excess hyperbaric levobupivacaine (s75: r25) provides unilateral spinal anesthesia. Study with different volumes.

Science.gov (United States)

Imbelloni, Luiz Eduardo; Gouveia, Marildo A; Carneiro, Antonio Fernando; Grigorio, Renata

2012-01-01

Unilateral spinal anesthesia may be obtained with hypobaric or hyperbaric solution. The objective of this study was to compare different doses of enantiomeric excess hyperbaric levobupivacaine to achieve unilateral spinal anesthesia. One hundred and twenty patients were randomized to receive 4 mg, 6 mg or 8 mg of 0.4% enantiomeric excess levobupivacaine. The solutions were administered at the L3-L4, with the patient in a lateral position and kept at this position according to dose administration for 5, 10 or 15 minutes. Sensory block (pinprick) and motor block (scale 0-3) were compared between the operated and contralateral sides. The onset of analgesia was rapid and comparable between groups. Sensory block was significantly higher in the operated than in nonoperated limb at all times of evaluation. Increasing the dose by 1 mL (2mg) corresponded to an increase of two segments in the mode for the operated side. In the operated side, motor block (MB = 3) of patients occurred in 31 (77.5%) with 4 mg, 38 (95%) with 6 mg, and 40 (100%) with 8 mg. There was a positive correlation between increased dose, blockade duration, and hypotension. All patients were satisfied with the technique used. Spinal anesthesia with different volumes of enantiomeric excess hyperbaric bupivacaine (S75: R25) provided a 78% incidence of unilateral spinal block, with the smallest dose used (4 mg) the most efficient. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds

International Nuclear Information System (INIS)

Kuzmenko, Volodymyr; Kalogeropoulos, Theodoros; Thunberg, Johannes; Johannesson, Sara; Hägg, Daniel; Enoksson, Peter; Gatenholm, Paul

2016-01-01

The problem of recovery from neurodegeneration needs new effective solutions. Tissue engineering is viewed as a prospective approach for solving this problem since it can help to develop healthy neural tissue using supportive scaffolds. This study presents effective and sustainable tissue engineering methods for creating biomaterials from cellulose that can be used either as scaffolds for the growth of neural tissue in vitro or as drug screening models. To reach this goal, nanofibrous electrospun cellulose mats were made conductive via two different procedures: carbonization and addition of multi-walled carbon nanotubes. The resulting scaffolds were much more conductive than untreated cellulose material and were used to support growth and differentiation of SH-SY5Y neuroblastoma cells. The cells were evaluated by scanning electron microscopy and confocal microscopy methods over a period of 15 days at different time points. The results showed that the cellulose-derived conductive scaffolds can provide support for good cell attachment, growth and differentiation. The formation of a neural network occurred within 10 days of differentiation, which is a promising length of time for SH-SY5Y neuroblastoma cells. - Highlights: • The conductive scaffolds for neural tissue engineering are derived from cellulose. • The scaffolds are used to support growth and differentiation of SH-SY5Y cells. • Distinctive cell differentiation occurs within 10 days on conductive scaffolds. • Electrical conductivity and nanotopography improve neural network formation.

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.

Mechanical properties and biocompatibility of porous titanium scaffolds for bone tissue engineering.

Science.gov (United States)

Chen, Yunhui; Frith, Jessica Ellen; Dehghan-Manshadi, Ali; Attar, Hooyar; Kent, Damon; Soro, Nicolas Dominique Mathieu; Bermingham, Michael J; Dargusch, Matthew S

2017-11-01

Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human cortical bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 44.2GPa, 24.7GPa and 15.4GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30GPa). The yield strengths for 30% and 40% porosity samples of 221.7MPa and 117MPa are superior to that of human cortical bone (130-180MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficient Computational Design of a Scaffold for Cartilage Cell Regeneration

DEFF Research Database (Denmark)

Tajsoleiman, Tannaz; Jafar Abdekhodaie, Mohammad; Gernaey, Krist V.

2018-01-01

Due to the sensitivity of mammalian cell cultures, understanding the influence of operating conditions during a tissue generation procedure is crucial. In this regard, a detailed study of scaffold based cell culture under a perfusion flow is presented with the aid of mathematical modelling...... and computational fluid dynamics (CFD). With respect to the complexity of the case study, this work focuses solely on the effect of nutrient and metabolite concentrations, and the possible influence of fluid-induced shear stress on a targeted cell (cartilage) culture. The simulation set up gives the possibility...... of predicting the cell culture behavior under various operating conditions and scaffold designs. Thereby, the exploitation of the predictive simulation into a newly developed stochastic routine provides the opportunity of exploring improved scaffold geometry designs. This approach was applied on a common type...

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.

A structural model for the flexural mechanics of nonwoven tissue engineering scaffolds.

Science.gov (United States)

Engelmayr, George C; Sacks, Michael S

2006-08-01

the need for structural approaches in modeling the effects of engineered tissue formation on nonwoven scaffolds, and their potential utility in scaffold design.

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.

Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

Science.gov (United States)

Hlavaty, K A; Gibly, R F; Zhang, X; Rives, C B; Graham, J G; Lowe, W L; Luo, X; Shea, L D

2014-07-01

Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Directing self-assembly of gold nanoparticles in diblock copolymer scaffold

Science.gov (United States)

Li, Qifang; He, Jinbo; Glogowski, Elizabeth; Emrick, Todd; Russell, Thomas

2007-03-01

A versatile hierarchical approach for directing self -assembly of gold nanostructures with size 2-3nm in diblock copolymer scaffolds is found. Diblock copolymer polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) is used to form a regular scaffold of highly anisotropic, stripe-like domains, and controlled differential wetting by dichloromethane and thermal annealing guides gold nanoparticles with half hydrophilic ligand to aggregate selectively along the scaffold, producing highly organized metal nanostructures. In as-cast block-copolymer and gold nanoparticles thin films, micelle structure and gold nanoparticles random distribution on scaffold are typically observed. However, samples annealed in dichloromethane exhibit well-defined short-range ordered nanostructure with gold nanoparticles located at the interface of PS and P2VP nanoscale domain. After annealing at 170 C, the gold nanoparticles at interface migrated into the middle of P2VP phase and exhibited long-range ordered hierarchical structures. Synergistic interactions between the gold nanoparticles and the PS-b-P2VP caused an orientation of the microdomains normal to the film surface.

Design and Fabrication of Biodegradable Porous Chitosan/Gelatin/Tricalcium Phosphate Hybrid Scaffolds for Tissue Engineering

Directory of Open Access Journals (Sweden)

Y. Mohammadi

2007-08-01

Full Text Available In this study, based on a biomimetic approach, novel 3D biodegradable porous hybrid scaffolds consisting of chitosan, gelatin, and tricalcium phosphate were developed for bone and cartilage tissue engineering. Macroporous chitosan/ gelatin/β-TCP scaffolds were prepared through the process of freeze-gelation/solid-liquid phase separation. The results showed that the prepared scaffolds are highly porous, with porosities larger than 80%, and have interconnected pores. Biocompatibility studies were successfully performed by in vitro and in vivo assays. Moreover, the attachment, migration, and proliferation of chondrocytes on these unique temporary scaffolds were examined to determine their potentials in tissue engineering applications.

VEGF-incorporated biomimetic poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering.

Science.gov (United States)

Jabbarzadeh, Ehsan; Deng, Meng; Lv, Qing; Jiang, Tao; Khan, Yusuf M; Nair, Lakshmi S; Laurencin, Cato T

2012-11-01

Regenerative engineering approaches utilizing biomimetic synthetic scaffolds provide alternative strategies to repair and restore damaged bone. The efficacy of the scaffolds for functional bone regeneration critically depends on their ability to induce and support vascular infiltration. In the present study, three-dimensional (3D) biomimetic poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds were developed by sintering together PLAGA microspheres followed by nucleation of minerals in a simulated body fluid. Further, the angiogenic potential of vascular endothelial growth factor (VEGF)-incorporated mineralized PLAGA scaffolds were examined by monitoring the growth and phenotypic expression of endothelial cells on scaffolds. Scanning electron microscopy micrographs confirmed the growth of bone-like mineral layers on the surface of microspheres. The mineralized PLAGA scaffolds possessed interconnectivity and a compressive modulus of 402 ± 61 MPa and compressive strength of 14.6 ± 2.9 MPa. Mineralized scaffolds supported the attachment and growth and normal phenotypic expression of endothelial cells. Further, precipitation of apatite layer on PLAGA scaffolds resulted in an enhanced VEGF adsorption and prolonged release compared to nonmineralized PLAGA and, thus, a significant increase in endothelial cell proliferation. Together, these results demonstrated the potential of VEGF-incorporated biomimetic PLAGA sintered microsphere scaffolds for bone tissue engineering as they possess the combined effects of osteointegrativity and angiogenesis. Copyright © 2012 Wiley Periodicals, Inc.

Design and fabrication of porous biodegradable scaffolds: a strategy for tissue engineering.

Science.gov (United States)

Raeisdasteh Hokmabad, Vahideh; Davaran, Soodabeh; Ramazani, Ali; Salehi, Roya

2017-11-01

Current strategies of tissue engineering are focused on the reconstruction and regeneration of damaged or deformed tissues by grafting of cells with scaffolds and biomolecules. Recently, much interest is given to scaffolds which are based on mimic the extracellular matrix that have induced the formation of new tissues. To return functionality of the organ, the presence of a scaffold is essential as a matrix for cell colonization, migration, growth, differentiation and extracellular matrix deposition, until the tissues are totally restored or regenerated. A wide variety of approaches has been developed either in scaffold materials and production procedures or cell sources and cultivation techniques to regenerate the tissues/organs in tissue engineering applications. This study has been conducted to present an overview of the different scaffold fabrication techniques such as solvent casting and particulate leaching, electrospinning, emulsion freeze-drying, thermally induced phase separation, melt molding and rapid prototyping with their properties, limitations, theoretical principles and their prospective in tailoring appropriate micro-nanostructures for tissue regeneration applications. This review also includes discussion on recent works done in the field of tissue engineering.

Isolation of Notoamide S and Enantiomeric 6-epi-Stephacidin A from the Fungus Aspergillus amoenus: Biogenetic Implications

DEFF Research Database (Denmark)

Kato, Hikaru; Nakahara, Takashi; Sugimoto, Kayo

2015-01-01

Notoamide S has been hypothesized to be a key biosynthetic intermediate for characteristic metabolites stephacidin A, notoamide B, and versicolamide B in Aspergillus sp. but has not yet been isolated. The isolation of notoamide S and an enantiomeric mixture of 6-epi-stephacidin A enriched with th...

Wet-Lay Process - A Novel Approach to Scalable Fabrication of Tissue Scaffolds and Reinforcement Membranes

Science.gov (United States)

Wood, Andrew

Fibrous materials received a great deal of interest in the fields of tissue engineering and regenerative medicine due to the beneficial cell-interactions and tunable properties for various biomedical applications. These materials are highly advantageous as they provide a large surface area for cellular attachment, proliferation, high porosity values for cellular in-growth, and the ability to modify the membrane to achieve desired responses to both mechanical loading as well as environmental stimuli. A prominent method currently used to fabricate such membranes is electrospinning which uses electrostatic forces to produce fibers on the range of nanometers giving them high morphological saliency to the native extra cellular matrix (ECM). These fibers are also advantageous mechanically with strength and flexibility due to their larger aspect ratio when compared to larger diameter micro/macro fibers. While this spinning technique has many advantages and has seen the most quantity of research in recent years, it does have its own set of drawbacks. Among them is the use cytotoxic solvents during processing which must be fully removed before implantation. In addition, since the fiber produced have smaller diameters, the resulting average pore-size of the scaffold is decreased which in turn hinders cellular penetration into the bulk scaffold. In this work, we have proposed and characterized a novel method called wet-lay process for the rapid fabrication of fibrous membranes for tissue scaffolds. Wet-laying is a method common to textiles and paper industry but unexplored for tissue scaffolds. Short fibers are first suspended in an aqueous bath and homogeneously dispersed using shear force. After draining away the aqueous solution, a nonwoven fibro-porous membrane is deposited onto the draining screen. The implementation of wet-laid membranes into weak hydrogel matrices has shown a reinforcement effect for the composite. Further analyses were carried out to determine the

HIV p24 as scaffold for presenting conformational HIV Env antigens.

Directory of Open Access Journals (Sweden)

Maria Tagliamonte

Full Text Available Heterologous protein scaffolds engrafted with structurally defined HIV Env epitopes recognized by broadly neutralizing monoclonal antibodies (MAbs represent a promising strategy to elicit broad neutralizing antibodies. In such regards, a protein scaffold based on the HIV p24 CA protein is a highly attractive approach, providing also Gag epitopes for eliciting HIV non-neutralizing protective antibodies and specific CD4(+ and CD8(+ T cell responses. In the present study, computational techniques were employed to verify the presence of acceptor sites for conformational HIV Env epitopes and, as proof of concept, the analysis of HIV p24 CA-based scaffolds using a complete V3 loop in a MAb-bound conformation is presented. The V3-p24 epitope-scaffold proteins show the formation of capsomers made of hexamers similarly to the p24 wild type protein. Moreover, the conformational V3 loop presented on p24 scaffold is recognized by a panel of anti-V3 MAbs. The results suggest that HIV p24 CA protein has suitable acceptor sites for engrafting foreign epitopes, without disrupting the formation of capsomer hexamer structures, and that the V3 epitope does retain its antibody-bound conformation. This strongly support the feasibility of developing a scaffolding strategy based on p24 CA proteins displaying conformational minimal structural, antigenic HIV Env epitopes.

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography.

Science.gov (United States)

Lin, Kuo-Shyan; Ding, Yu-Shin; Kim, Sung-Won; Kil, Kun-Eek

2005-05-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[alpha-(2-(2-[(18)F]fluoroethoxy)phenoxy)benzyl]morpholine ([(18)F]FRB) and its tetradeuterated form [(18)F]FRB-D(4), analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [(18)F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [(18)F]FRB and [(18)F]FRB-D(4) via the following three-step procedure: (1) formation of 1-bromo-2-[(18)F]fluoroethane ([(18)F]BFE or [(18)F]BFE-D(4)) by nucleophilic displacement of 2-bromoethyl triflate (or D(4) analog) with no-carrier added [(18)F]F(-) in THF; (2) reaction of [(18)F]BFE (or [(18)F]BFE-D(4)) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [(18)F]FRB and [(18)F]FRB-D(4) were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/micromol (EOB). The results of the whole-body biodistribution studies with (S,S)-[(18)F]FRB-D(4) were similar to those with (S,S)-[(18)F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[(18)F]FRB-D(4) may be a potentially useful ligand for imaging NET with PET.

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography

International Nuclear Information System (INIS)

Lin, K.-S.; Ding, Y.-S.; Kim, Sung-Won; Kil, Kun-Eek

2005-01-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[α-(2-(2-[ 18 F]fluoroethoxy)phenoxy)benzyl]morpholine ([ 18 F]FRB) and its tetradeuterated form [ 18 F]FRB-D 4 , analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[α-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [ 18 F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[α-(2-hydroxyphenoxy)benzyl] morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[α-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [ 18 F]FRB and [ 18 F]FRB-D 4 via the following three-step procedure: (1) formation of 1-bromo-2-[ 18 F]fluoroethane ([ 18 F]BFE or [ 18 F]BFE-D 4 ) by nucleophilic displacement of 2-bromoethyl triflate (or D 4 analog) with no-carrier added [ 18 F]F - in THF; (2) reaction of [ 18 F]BFE (or [ 18 F]BFE-D 4 ) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [ 18 F]FRB and [ 18 F]FRB-D 4 were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/μmol (EOB). The results of the whole-body biodistribution studies with (S,S)-[ 18 F]FRB-D 4 were similar to those with (S,S)-[ 18 F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[ 18 F]FRB-D 4 may be a potentially useful ligand for imaging NET with PET

In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering.

Science.gov (United States)

Jiang, Tao; Abdel-Fattah, Wafa I; Laurencin, Cato T

2006-10-01

A three-dimensional (3-D) scaffold is one of the major components in many tissue engineering approaches. We developed novel 3-D chitosan/poly(lactic acid-glycolic acid) (PLAGA) composite porous scaffolds by sintering together composite chitosan/PLAGA microspheres for bone tissue engineering applications. Pore sizes, pore volume, and mechanical properties of the scaffolds can be manipulated by controlling fabrication parameters, including sintering temperature and sintering time. The sintered microsphere scaffolds had a total pore volume between 28% and 37% with median pore size in the range 170-200microm. The compressive modulus and compressive strength of the scaffolds are in the range of trabecular bone making them suitable as scaffolds for load-bearing bone tissue engineering. In addition, MC3T3-E1 osteoblast-like cells proliferated well on the composite scaffolds as compared to PLAGA scaffolds. It was also shown that the presence of chitosan on microsphere surfaces increased the alkaline phosphatase activity of the cells cultured on the composite scaffolds and up-regulated gene expression of alkaline phosphatase, osteopontin, and bone sialoprotein.

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...

Micro-CT based finite element models for elastic properties of glass-ceramic scaffolds.

Science.gov (United States)

Tagliabue, Stefano; Rossi, Erica; Baino, Francesco; Vitale-Brovarone, Chiara; Gastaldi, Dario; Vena, Pasquale

2017-01-01

In this study, the mechanical properties of porous glass-ceramic scaffolds are investigated by means of three-dimensional finite element models based on micro-computed tomography (micro-CT) scan data. In particular, the quantitative relationship between the morpho-architectural features of the obtained scaffolds, such as macroscopic porosity and strut thickness, and elastic properties, is sought. The macroscopic elastic properties of the scaffolds have been obtained through numerical homogenization approaches using the mechanical characteristics of the solid walls of the scaffolds (assessed through nanoindentation) as input parameters for the numerical simulations. Anisotropic mechanical properties of the produced scaffolds have also been investigated by defining a suitable anisotropy index. A comparison with morphological data obtained through the micro-CT scans is also presented. The proposed study shows that the produced glass-ceramic scaffolds exhibited a macroscopic porosity ranging between 29% and 97% which corresponds to an average stiffness ranging between 42.4GPa and 36MPa. A quantitative estimation of the isotropy of the macroscopic elastic properties has been performed showing that the samples with higher solid fractions were those closest to an isotropic material. Copyright © 2016 Elsevier Ltd. All rights reserved.

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;.

Living bacterial sacrificial porogens to engineer decellularized porous scaffolds.

Directory of Open Access Journals (Sweden)

Feng Xu

Full Text Available Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types.

Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Jahnavi, S [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Saravanan, U [Department of Civil Engineering, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Arthi, N [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Bhuvaneshwar, G S [Department of Engineering Design, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Kumary, T V [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Rajan, S [Madras Medical Mission, Institute of Cardio-Vascular Diseases, Mogappair, Chennai, Tamil Nadu 600037 (India); Verma, R S, E-mail: vermars@iitm.ac.in [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India)

2017-04-01

Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44{sup +}, αSMA{sup +}, Vimentin{sup +} and CD105{sup −} human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. - Highlights: • We report detailed biological and mechanical investigations of a Bio-Hybrid scaffold. • Optimized polymer thickness yielded desired biological and mechanical properties. • Bio-Hybrid scaffold revealed hVIC proliferation with dense ECM deposition. • Biaxial testing indicated that Bio-Hybrid scaffolds are mechanically stronger than native valves. • Bio-Hybrid scaffold is a promising material for autologous valve tissue engineering.

Enantiomeric profiling of chiral illicit drugs in a pan-European study

DEFF Research Database (Denmark)

Castrignanò, Erika; Yang, Zhugen; Bade, Richard

2018-01-01

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context....... High loads of racemic methamphetamine were detected in Oslo (EF = 0.49 ± 0.02). This is in contrast to other European cities where S-(+)-methamphetamine was the predominant enantiomer. This indicates different methods of methamphetamine synthesis and/or trafficking routes in Oslo, compared...... with the other cities tested. An enrichment of MDMA with the R-(−)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans...

Fabrication of tissue engineering scaffolds through solid-state foaming of immiscible polymer blends

International Nuclear Information System (INIS)

Zhou Changchun; Li Wei; Ma Liang; Yao Donggang

2011-01-01

In scaffold-based tissue engineering, the fabrication process is important for producing suitable microstructures for seeded cells to grow and reformulate. In this paper, we present a new approach to scaffold fabrication by combining the solid-state foaming and the immiscible polymer-blending method. The proposed approach has the advantage of being versatile and able to create a wide range of pore size and porosity. The proposed method is studied with polylactic acid (PLA) and polystyrene (PS) blends. The interconnected porous structure was created by first foaming the PLA/PS blend and then extracting the PS phase. The solid-state foaming experiments were conducted under various conditions to achieve the desired pore sizes. It is shown that the PS phase of the PLA/PS blend can be extracted much faster in the foamed samples and the pore size of the scaffolds can be easily controlled with proper gas foaming parameters. The average pore size achieved in the foaming process ranged from 20 to 70 μm. After PS extraction, both pore size and porosity can be further improved. For example, the pore size and porosity increased from 48 μm and 49% to 59 μm and 67%, respectively, after the PS extraction process. The fabricated porous scaffolds were used to culture human osteoblast cells. Cells grew well and gradually formed a fibrous structure. The combined solid-state foaming and immiscible polymer blending method provides a new technique for fabricating tissue-engineering scaffolds.

Increasing the strength and bioactivity of collagen scaffolds using customizable arrays of 3D-printed polymer fibers.

Science.gov (United States)

Mozdzen, Laura C; Rodgers, Ryan; Banks, Jessica M; Bailey, Ryan C; Harley, Brendan A C

2016-03-01

Tendon is a highly aligned connective tissue which transmits force from muscle to bone. Each year, people in the US sustain more than 32 million tendon injuries. To mitigate poor functional outcomes due to scar formation, current surgical techniques rely heavily on autografts. Biomaterial platforms and tissue engineering methods offer an alternative approach to address these injuries. Scaffolds incorporating aligned structural features can promote expansion of adult tenocytes and mesenchymal stem cells capable of tenogenic differentiation. However, appropriate balance between scaffold bioactivity and mechanical strength of these constructs remains challenging. The high porosity required to facilitate cell infiltration, nutrient and oxygen biotransport within three-dimensional constructs typically results in insufficient biomechanical strength. Here we describe the use of three-dimensional printing techniques to create customizable arrays of acrylonitrile butadiene styrene (ABS) fibers that can be incorporated into a collagen scaffold under development for tendon repair. Notably, mechanical performance of scaffold-fiber composites (elastic modulus, peak stress, strain at peak stress, and toughness) can be selectively manipulated by varying fiber-reinforcement geometry without affecting the native bioactivity of the collagen scaffold. Further, we report an approach to functionalize ABS fibers with activity-inducing growth factors via sequential oxygen plasma and carbodiimide crosslinking treatments. Together, we report an adaptable approach to control both mechanical strength and presence of biomolecular cues in a manner orthogonal to the architecture of the collagen scaffold itself. Tendon injuries account for more than 32 million injuries each year in the US alone. Current techniques use allografts to mitigate poor functional outcomes, but are not ideal platforms to induce functional regeneration following injury. Tissue engineering approaches using biomaterial

Study of Substituted Ester Formation in Red Wine by the Development of a New Method for Quantitative Determination and Enantiomeric Separation of Their Corresponding Acids.

Science.gov (United States)

Lytra, Georgia; Franc, Celine; Cameleyre, Margaux; Barbe, Jean-Christophe

2017-06-21

A new method was developed for quantifying substituted acids including, where applicable, their various unexplored enantiomeric forms. A new step was added to acids' usual quantification methods, consisting of extraction, derivatization to methyl esters, and gas chromatography analysis: preliminary extraction was performed at basic pH to eliminate ethyl esters, thus avoiding their transesterification during derivatization. Quantitation and enantiomeric distribution of some substituted esters and their corresponding acids were established in 31 commercial Bordeaux red wines from 0 to 20 years old. A strong positive correlation was observed between the age of wine and levels of ethyl 2-methylpropanoate, ethyl 3-methylbutanoate, ethyl 2-methylbutanoate, ethyl (3R)-3-hydroxybutanoate, both enantiomeric forms of ethyl 2-hydroxy-3-methylbutanoate, and ethyl (2S)-2-hydroxy-4-methylpentanoate, but not ethyl (3S)-3-hydroxybutanoate. However, the standard deviations of average concentrations for the corresponding substituted acids were so large that only few correlations between concentrations and age were observed. Concentrations of (2S)-2-hydroxy-3-methylbutanoic acid and (2S)-2-hydroxy-4-methylpentanoic acid increased slightly over time, while (2R)-2-hydroxy-4-methylpentanoic acid levels decreased slightly with the age. Variations in the ratio of substituted ethyl esters to their corresponding acids over time detected thanks to these analytical advances suggested that, in general, acids were continuously esterified during aging.

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...

Fish collagen/alginate/chitooligosaccharides integrated scaffold for skin tissue regeneration application.

Science.gov (United States)

Chandika, Pathum; Ko, Seok-Chun; Oh, Gun-Woo; Heo, Seong-Yeong; Nguyen, Van-Tinh; Jeon, You-Jin; Lee, Bonggi; Jang, Chul Ho; Kim, GeunHyung; Park, Won Sun; Chang, Wonseok; Choi, Il-Whan; Jung, Won-Kyo

2015-11-01

An emerging paradigm in wound healing techniques is that a tissue-engineered skin substitute offers an alternative approach to create functional skin tissue. Here we developed a fish collagen/alginate (FCA) sponge scaffold that was functionalized by different molecular weights of chitooligosaccharides (COSs) with the use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a cross-linking agent. The effects of cross-linking were analyzed by Fourier transform infrared spectroscopy. The results indicate that the homogeneous materials blending and cross-linking intensity were dependent on the molecular weights of COSs. The highly interconnected porous architecture with 160-260μm pore size and over 90% porosity and COS's MW driven swelling and retention capacity, tensile property and in vitro biodegradation behavior guaranteed the FCA/COS scaffolds for skin tissue engineering application. Further improvement of these properties enhanced the cytocompatibility of all the scaffolds, especially the scaffolds containing COSs with MW in the range of 1-3kDa (FCA/COS1) showed the best cytocompatibility. These physicochemical, mechanical, and biological properties suggest that the FCA/COS1 scaffold is a superior candidate that can be used for skin tissue regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

Fabrication and characterization of novel nano-biocomposite scaffold of chitosan–gelatin–alginate–hydroxyapatite for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Sharma, Chhavi, E-mail: chhavisharma19@gmail.com [Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee (India); Dinda, Amit Kumar, E-mail: amit_dinda@yahoo.com [Department of Molecular Medicine and Biology, Jaslok Hospital and Research Centre, Mumbai 400 026 (India); Potdar, Pravin D., E-mail: ppotdar@jaslokhospital.net [Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029 (India); Chou, Chia-Fu, E-mail: cfchou@phys.sinica.edu.tw [Institute of Physics, Academia Sinica, Taipei 11529, Taiwan (China); Mishra, Narayan Chandra, E-mail: mishrawise@gmail.com [Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee (India)

2016-07-01

A novel nano-biocomposite scaffold was fabricated in bead form by applying simple foaming method, using a combination of natural polymers–chitosan, gelatin, alginate and a bioceramic–nano-hydroxyapatite (nHAp). This approach of combining nHAp with natural polymers to fabricate the composite scaffold, can provide good mechanical strength and biological property mimicking natural bone. Environmental scanning electron microscopy (ESEM) images of the nano-biocomposite scaffold revealed the presence of interconnected pores, mostly spread over the whole surface of the scaffold. The nHAp particulates have covered the surface of the composite matrix and made the surface of the scaffold rougher. The scaffold has a porosity of 82% with a mean pore size of 112 ± 19.0 μm. Swelling and degradation studies of the scaffold showed that the scaffold possesses excellent properties of hydrophilicity and biodegradability. Short term mechanical testing of the scaffold does not reveal any rupturing after agitation under physiological conditions, which is an indicative of good mechanical stability of the scaffold. In vitro cell culture studies by seeding osteoblast cells over the composite scaffold showed good cell viability, proliferation rate, adhesion and maintenance of osteoblastic phenotype as indicated by MTT assay, ESEM of cell–scaffold construct, histological staining and gene expression studies, respectively. Thus, it could be stated that the nano-biocomposite scaffold of chitosan–gelatin–alginate–nHAp has the paramount importance for applications in bone tissue-engineering in future regenerative therapies. - Highlights: • nHAp–chitosan–gelatin–alginate composite scaffold was successfully fabricated. • Foaming method, without surfactant, was applied successfully for fabricating the scaffold. • nHAp provided mechanical stability and nanotopographic features to scaffold matrix. • This scaffold shows good biocompatibility and proliferation with

Determination of the Absolute Enantiomeric Excess of the Carbon Nanotube Ensemble by Symmetry Breaking Using the Optical Titration Method.

Science.gov (United States)

Sim, Jinsook; Kim, Somin; Jang, Myungsu; Park, Minsuk; Oh, Hyunkyu; Ju, Sang-Yong

2017-10-17

Symmetry breaking of single-walled carbon nanotubes (SWNTs) has profound effects on their optoelectronic properties that are essential for fundamental study and applications. Here, we show that isomeric SWNTs that exhibit identical photoluminescence (PL) undergo symmetry breaking by flavin mononucleotide (FMN) and exhibit dual PLs and different binding affinities (K a ). Increasing the FMN concentration leads to systematic PL shifts of SWNTs according to structural modality and handedness due to symmetry breaking. Density gradient ultracentrifugation using a FMN-SWNT dispersion displays PL shifts and different densities according to SWNT handedness. Using the optical titration method to determine the PL-based K a of SWNTs against an achiral surfactant as a titrant, left- and right-handed SWNTs display two-step PL inflection corresponding to respective K a values with FMN, which leads to the determination of the enantiomeric excess (ee) of the SWNT ensemble that was confirmed by circular dichroism measurement. Decreasing the FMN concentration for the SWNT dispersion leads to enantiomeric selection of SWNTs. The titration-based ee determination of the widely used sodium cholate-based SWNT dispersion was also demonstrated by using FMN as a cosurfactant.

BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

Science.gov (United States)

Gao, Mingyong; Lu, Paul; Lynam, Dan; Bednark, Bridget; Campana, W. Marie; Sakamoto, Jeff; Tuszynski, Mark

2016-12-01

Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.

Hydrogel-laden paper scaffold system for origami-based tissue engineering.

Science.gov (United States)

Kim, Su-Hwan; Lee, Hak Rae; Yu, Seung Jung; Han, Min-Eui; Lee, Doh Young; Kim, Soo Yeon; Ahn, Hee-Jin; Han, Mi-Jung; Lee, Tae-Ik; Kim, Taek-Soo; Kwon, Seong Keun; Im, Sung Gap; Hwang, Nathaniel S

2015-12-15

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering.

Science.gov (United States)

Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S

2017-04-01

Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44 + , αSMA + , Vimentin + and CD105 - human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Effects of Faded Scaffolding in Computer-Based Instruction on Learners' Performance, Cognitive Load, and Test Anxiety

Science.gov (United States)

Hao, Shuang

2016-01-01

Scaffolding is a type of instructional support that helps students to complete a learning task that exceeds their current ability. Scaffolding plays an important role in augmenting other instructional approaches, such as problem-based learning, and facilitates gradual shifts of responsibility from the more advanced others to the learner (Belland,…

Disrupting the Scaffold to Improve Focal Adhesion Kinase–Targeted Cancer Therapeutics

Science.gov (United States)

Cance, William G.; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

2013-01-01

Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer. PMID:23532331

Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.

Science.gov (United States)

Cance, William G; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

2013-03-26

Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer.

Impact of scaffold micro and macro architecture on Schwann cell proliferation under dynamic conditions in a rotating wall vessel bioreactor

International Nuclear Information System (INIS)

Valmikinathan, Chandra M.; Hoffman, John; Yu, Xiaojun

2011-01-01

Over the last decade tissue engineering has emerged as a powerful alternative to regenerate lost tissues owing to trauma or tumor. Evidence shows that Schwann cell containing scaffolds have improved performance in vivo as compared to scaffolds that depend on cellularization post implantation. However, owing to limited supply of cells from the patients themselves, several approaches have been taken to enhance cell proliferation rates to produce complete and uniform cellularization of scaffolds. The most common approach is the application of a bioreactor to enhance cell proliferation rate and therefore reduce the time needed to obtain sufficiently significant number of glial cells, prior to implantation. In this study, we show the application of a rotating wall bioreactor system for studying Schwann cell proliferation on nanofibrous spiral shaped scaffolds, prepared by solvent casting and salt leaching techniques. The scaffolds were fabricated from polycaprolactone (PCL), which has ideal mechanical properties and upon degradation does not produce acidic byproducts. The spiral scaffolds were coated with aligned or random nanofibers, produced by electrospinning, to provide a substrate that mimics the native extracellular matrix and the essential contact guidance cues. At the 4 day time point, an enhanced rate of cell proliferation was observed on the open structured nanofibrous spiral scaffolds in a rotating wall bioreactor, as compared to static culture conditions. However, the cell proliferation rate on the other contemporary scaffolds architectures such as the tubular and cylindrical scaffolds show reduced cell proliferation in the bioreactor as compared to static conditions, at the same time point. Moreover, the rotating wall bioreactor does not alter the orientation or the phenotype of the Schwann cells on the aligned nanofiber containing scaffolds, wherein, the cells remain aligned along the length of the scaffolds. Therefore, these open structured spiral

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.

Design and characterization of microcapsules-integrated collagen matrixes as multifunctional three-dimensional scaffolds for soft tissue engineering.

Science.gov (United States)

Del Mercato, Loretta L; Passione, Laura Gioia; Izzo, Daniela; Rinaldi, Rosaria; Sannino, Alessandro; Gervaso, Francesca

2016-09-01

Three-dimensional (3D) porous scaffolds based on collagen are promising candidates for soft tissue engineering applications. The addition of stimuli-responsive carriers (nano- and microparticles) in the current approaches to tissue reconstruction and repair brings about novel challenges in the design and conception of carrier-integrated polymer scaffolds. In this study, a facile method was developed to functionalize 3D collagen porous scaffolds with biodegradable multilayer microcapsules. The effects of the capsule charge as well as the influence of the functionalization methods on the binding efficiency to the scaffolds were studied. It was found that the binding of cationic microcapsules was higher than that of anionic ones, and application of vacuum during scaffolds functionalization significantly hindered the attachment of the microcapsules to the collagen matrix. The physical properties of microcapsules-integrated scaffolds were compared to pristine scaffolds. The modified scaffolds showed swelling ratios, weight losses and mechanical properties similar to those of unmodified scaffolds. Finally, in vitro diffusional tests proved that the collagen scaffolds could stably retain the microcapsules over long incubation time in Tris-HCl buffer at 37°C without undergoing morphological changes, thus confirming their suitability for tissue engineering applications. The obtained results indicate that by tuning the charge of the microcapsules and by varying the fabrication conditions, collagen scaffolds patterned with high or low number of microcapsules can be obtained, and that the microcapsules-integrated scaffolds fully retain their original physical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

3D printing for the design and fabrication of polymer-based gradient scaffolds.

Science.gov (United States)

Bracaglia, Laura G; Smith, Brandon T; Watson, Emma; Arumugasaamy, Navein; Mikos, Antonios G; Fisher, John P

2017-07-01

To accurately mimic the native tissue environment, tissue engineered scaffolds often need to have a highly controlled and varied display of three-dimensional (3D) architecture and geometrical cues. Additive manufacturing in tissue engineering has made possible the development of complex scaffolds that mimic the native tissue architectures. As such, architectural details that were previously unattainable or irreproducible can now be incorporated in an ordered and organized approach, further advancing the structural and chemical cues delivered to cells interacting with the scaffold. This control over the environment has given engineers the ability to unlock cellular machinery that is highly dependent upon the intricate heterogeneous environment of native tissue. Recent research into the incorporation of physical and chemical gradients within scaffolds indicates that integrating these features improves the function of a tissue engineered construct. This review covers recent advances on techniques to incorporate gradients into polymer scaffolds through additive manufacturing and evaluate the success of these techniques. As covered here, to best replicate different tissue types, one must be cognizant of the vastly different types of manufacturing techniques available to create these gradient scaffolds. We review the various types of additive manufacturing techniques that can be leveraged to fabricate scaffolds with heterogeneous properties and discuss methods to successfully characterize them. Additive manufacturing techniques have given tissue engineers the ability to precisely recapitulate the native architecture present within tissue. In addition, these techniques can be leveraged to create scaffolds with both physical and chemical gradients. This work offers insight into several techniques that can be used to generate graded scaffolds, depending on the desired gradient. Furthermore, it outlines methods to determine if the designed gradient was achieved. This review

Engineering bone grafts with enhanced bone marrow and native scaffolds.

Science.gov (United States)

Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

2013-01-01

The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds. © 2013 S. Karger AG, Basel

Mechanical behaviour of a fibrous scaffold for ligament tissue engineering: finite elements analysis vs. X-ray tomography imaging.

Science.gov (United States)

Laurent, Cédric P; Latil, Pierre; Durville, Damien; Rahouadj, Rachid; Geindreau, Christian; Orgéas, Laurent; Ganghoffer, Jean-François

2014-12-01

The use of biodegradable scaffolds seeded with cells in order to regenerate functional tissue-engineered substitutes offers interesting alternative to common medical approaches for ligament repair. Particularly, finite element (FE) method enables the ability to predict and optimise both the macroscopic behaviour of these scaffolds and the local mechanic signals that control the cell activity. In this study, we investigate the ability of a dedicated FE code to predict the geometrical evolution of a new braided and biodegradable polymer scaffold for ligament tissue engineering by comparing scaffold geometries issued from FE simulations and from X-ray tomographic imaging during a tensile test. Moreover, we compare two types of FE simulations the initial geometries of which are issued either from X-ray imaging or from a computed idealised configuration. We report that the dedicated FE simulations from an idealised reference configuration can be reasonably used in the future to predict the global and local mechanical behaviour of the braided scaffold. A valuable and original dialog between the fields of experimental and numerical characterisation of such fibrous media is thus achieved. In the future, this approach should enable to improve accurate characterisation of local and global behaviour of tissue-engineering scaffolds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

DEFF Research Database (Denmark)

Leurs, Ulrike; Clausen, Rasmus P; Kristensen, Jesper L

2012-01-01

The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat...... cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel...... therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation....

Limitations in determining enantiomeric excess of alcohols by 31 P-NMR of the phosphonate derivatives

International Nuclear Information System (INIS)

Laverde Junior, Antonio; Conceicao, Jelson J.A. da; Pilli, Ronaldo A.; Marsaioli, Anita J.; Miranda, Domingos S. de; Schirmer, Heiko; Meijere, Armin de

1999-01-01

The use of diastereomeric alcohol dialkyl-phosphonate derivatives to determine the enantiomeric excesses via 31 P-NMR signal ratios of anisochronous meso and threo isomers was successfully applied to secondary alcohols (Feringa's method). Expansion of the methodology to primary alcohols processing the hydroxyl groups tethered to the stereogenic centers by two or more methylene groups proved the method to be inefficient. The comparison between the coupled and decoupled spectra is important in order to identify the signals corresponding to the dialkyl-phosphonates. Nevertheless the methodology should be applied whenever the amount of the alcohol and its structure are not the limiting factors. (author)

Biocomposite scaffolds based on electrospun poly(3-hydroxybutyrate) nanofibers and electrosprayed hydroxyapatite nanoparticles for bone tissue engineering applications

International Nuclear Information System (INIS)

Ramier, Julien; Bouderlique, Thibault; Stoilova, Olya; Manolova, Nevena; Rashkov, Iliya; Langlois, Valérie; Renard, Estelle; Albanese, Patricia; Grande, Daniel

2014-01-01

The electrospinning technique combined with the electrospraying process provides a straightforward and versatile approach for the fabrication of novel nanofibrous biocomposite scaffolds with structural, mechanical, and biological properties potentially suitable for bone tissue regeneration. In this comparative investigation, three types of poly(3-hydroxybutyrate) (PHB)-based scaffolds were engineered: (i) PHB mats by electrospinning of a PHB solution, (ii) mats of PHB/hydroxyapatite nanoparticle (nHA) blends by electrospinning of a mixed solution containing PHB and nHAs, and (iii) mats constituted of PHB nanofibers and nHAs by simultaneous electrospinning of a PHB solution and electrospraying of a nHA dispersion. Scaffolds based on PHB/nHA blends displayed improved mechanical properties compared to those of neat PHB mats, due to the incorporation of nHAs within the fibers. The electrospinning/electrospraying approach afforded biocomposite scaffolds with lower mechanical properties, due to their higher porosity, but they displayed slightly better biological properties. In the latter case, the bioceramic, i.e. nHAs, largely covered the fiber surface, thus allowing for a direct exposure to cells. The 21 day-monitoring through the use of MTS assays and SEM analyses demonstrated that human mesenchymal stromal cells (hMSCs) remained viable on PHB/nHA biocomposite scaffolds and proliferated continuously until reaching confluence. - Highlights: • Three different types of PHB-based scaffolds are engineered and thoroughly investigated. • The combination of electrospinning and electrospraying affords original nanofibrous biocomposite scaffolds. • PHB-based scaffolds show a strong capability of supporting viable cell development for 21 days

Biocomposite scaffolds based on electrospun poly(3-hydroxybutyrate) nanofibers and electrosprayed hydroxyapatite nanoparticles for bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Ramier, Julien [Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS, Université Paris-Est Créteil, 2, rue Henri Dunant, 94320 Thiais (France); Bouderlique, Thibault [Laboratoire “Croissance, Réparation et Régénération Tissulaires”, EAC 7149 CNRS, Université Paris-Est Créteil, 61, avenue du Général de Gaulle, 94010 Créteil (France); Stoilova, Olya; Manolova, Nevena; Rashkov, Iliya [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St., bl. 103A, BG-1113 Sofia (Bulgaria); Langlois, Valérie; Renard, Estelle [Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS, Université Paris-Est Créteil, 2, rue Henri Dunant, 94320 Thiais (France); Albanese, Patricia [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St., bl. 103A, BG-1113 Sofia (Bulgaria); Grande, Daniel, E-mail: grande@icmpe.cnrs.fr [Institut de Chimie et des Matériaux Paris-Est, UMR 7182 CNRS, Université Paris-Est Créteil, 2, rue Henri Dunant, 94320 Thiais (France)

2014-05-01

The electrospinning technique combined with the electrospraying process provides a straightforward and versatile approach for the fabrication of novel nanofibrous biocomposite scaffolds with structural, mechanical, and biological properties potentially suitable for bone tissue regeneration. In this comparative investigation, three types of poly(3-hydroxybutyrate) (PHB)-based scaffolds were engineered: (i) PHB mats by electrospinning of a PHB solution, (ii) mats of PHB/hydroxyapatite nanoparticle (nHA) blends by electrospinning of a mixed solution containing PHB and nHAs, and (iii) mats constituted of PHB nanofibers and nHAs by simultaneous electrospinning of a PHB solution and electrospraying of a nHA dispersion. Scaffolds based on PHB/nHA blends displayed improved mechanical properties compared to those of neat PHB mats, due to the incorporation of nHAs within the fibers. The electrospinning/electrospraying approach afforded biocomposite scaffolds with lower mechanical properties, due to their higher porosity, but they displayed slightly better biological properties. In the latter case, the bioceramic, i.e. nHAs, largely covered the fiber surface, thus allowing for a direct exposure to cells. The 21 day-monitoring through the use of MTS assays and SEM analyses demonstrated that human mesenchymal stromal cells (hMSCs) remained viable on PHB/nHA biocomposite scaffolds and proliferated continuously until reaching confluence. - Highlights: • Three different types of PHB-based scaffolds are engineered and thoroughly investigated. • The combination of electrospinning and electrospraying affords original nanofibrous biocomposite scaffolds. • PHB-based scaffolds show a strong capability of supporting viable cell development for 21 days.

MacroEvoLution: A New Method for the Rapid Generation of Novel Scaffold-Diverse Macrocyclic Libraries.

Science.gov (United States)

Saupe, Jörn; Kunz, Oliver; Haustedt, Lars Ole; Jakupovic, Sven; Mang, Christian

2017-09-04

Macrocycles are a structural class bearing great promise for future challenges in medicinal chemistry. Nevertheless, there are few flexible approaches for the rapid generation of structurally diverse macrocyclic compound collections. Here, an efficient method for the generation of novel macrocyclic peptide-based scaffolds is reported. The process, named here as "MacroEvoLution", is based on a cyclization screening approach that gives reliable access to novel macrocyclic architectures. Classification of building blocks into specific pools ensures that scaffolds with orthogonally addressable functionalities are generated, which can easily be used for the generation of structurally diverse compound libraries. The method grants rapid access to novel scaffolds with scalable synthesis (multi gram scale) and the introduction of further diversity at a late stage. Despite being developed for peptidic systems, the approach can easily be extended for the synthesis of systems with a decreased peptidic character. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Site-Directed Immobilization of BMP-2: Two Approaches for the Production of Innovative Osteoinductive Scaffolds.

Science.gov (United States)

Tabisz, Barbara; Schmitz, Werner; Schmitz, Michael; Luehmann, Tessa; Heusler, Eva; Rybak, Jens-Christoph; Meinel, Lorenz; Fiebig, Juliane E; Mueller, Thomas D; Nickel, Joachim

2017-03-13

The regenerative potential of bone is strongly impaired in pathological conditions, such as nonunion fractures. To support bone regeneration various scaffolds have been developed in the past, which have been functionalized with osteogenic growth factors such as bone morphogenetic proteins (BMPs). However, most of them required supra-physiological levels of these proteins leading to burst releases, thereby causing severe side effects. Site-specific, covalent coupling of BMP2 to implant materials might be an optimal strategy in order to overcome these problems. Therefore, we created a BMP-2 variant (BMP2-K3Plk) containing a noncanonical amino acid (propargyl-l-lysine) substitution introduced by genetic code expansion that allows for site-specific and covalent immobilization onto polymeric scaffold materials. To directly compare different coupling strategies, we also produced a BMP2 variant containing an additional cysteine residue (BMP2-A2C) allowing covalent coupling by thioether formation. The BMP2-K3Plk mutant was coupled to functionalized beads by a copper-catalyzed azide-alkyne cycloaddition (CuAAC) either directly or via a short biotin-PEG linker both with high specificity. After exposing the BMP-coated beads to C2C12 cells, ALP expression appeared locally restricted in close proximity to these beads, showing that both coupled BMP2 variants trigger cell differentiation. The advantage of our approach over non-site-directed immobilization techniques is the ability to produce fully defined osteogenic surfaces, allowing for lower BMP2 loads and concomitant higher bioactivities, for example, due to controlled orientation toward BMP2 receptors. Such products might provide superior bone healing capabilities with potential safety advantages as of homogeneous product outcome.

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Lin, K.-S. [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Ding, Y.-S. [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States)]. E-mail: ding@bnl.gov; Kim, Sung-Won [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Kil, Kun-Eek [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States)

2005-05-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[{alpha}-(2-(2-[{sup 18}F]fluoroethoxy)phenoxy)benzyl]morpholine ([{sup 18}F]FRB) and its tetradeuterated form [{sup 18}F]FRB-D{sub 4}, analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[{alpha}-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [{sup 18}F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[{alpha}-(2-hydroxyphenoxy)benzyl] morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[{alpha}-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [{sup 18}F]FRB and [{sup 18}F]FRB-D{sub 4} via the following three-step procedure: (1) formation of 1-bromo-2-[{sup 18}F]fluoroethane ([{sup 18}F]BFE or [{sup 18}F]BFE-D{sub 4}) by nucleophilic displacement of 2-bromoethyl triflate (or D{sub 4} analog) with no-carrier added [{sup 18}F]F{sup -} in THF; (2) reaction of [{sup 18}F]BFE (or [{sup 18}F]BFE-D{sub 4}) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [{sup 18}F]FRB and [{sup 18}F]FRB-D{sub 4} were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/{mu}mol (EOB). The results of the whole-body biodistribution studies with (S,S)-[{sup 18}F]FRB-D{sub 4} were similar to those with (S,S)-[{sup 18}F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also

Manufacturing of calcium phosphate scaffolds by pseudomorphic transformation of gypsum

Energy Technology Data Exchange (ETDEWEB)

Araujo Batista, H. de.; Batista Cardoso, M.; Sales Vasconcelos, A.; Vinicius Lia Fook, M.; Rodriguez Barbero, M. A.; Garcia Carrodeguas, R.

2016-08-01

Carbonated hydroxyapatite (CHAp) and β-tricalcium phosphate (β-TCP) have been employed for decades as constituents of scaffolds for bone regeneration because they chemically resemble bone mineral. In this study, the feasibility to manufacture CHAp/β-TCP scaffolds by pseudomorphic transformation of casted blocks of gypsum was investigated. The transformation was carried out by immersing the precursor gypsum block in 1 M (NH{sub 4}){sub 2}HPO{sub 4}/1.33 M NH{sub 4}OH solution with liquid/solid ratio of 10 mL/g and autoclaving at 120 degree centigrade and 203 kPa (2 atm) for 3 h at least. Neither shape nor dimensions significantly changed during transformation. The composition of scaffolds treated for 3 h was 70 wt.% CHAp and 30 wt.% β-TCP, and their compressive and diametral compressive strengths were 6.5 ± 0.7 and 5.3 ±0.7 MPa, respectively. By increasing the time of treatment to 6 h, the composition of the scaffold enriched in β-TCP (60 wt.% CHAp and 40 wt.% β-TCP) but its compressive and diametral compressive strengths were not significantly affected (6.7 ± 0.9 and 5.4 ± 0.6 MPa, respectively). On the basis of the results obtained, it was concluded that this route is a good approach to the manufacturing of biphasic (CHAp/β-TCP) scaffolds from previously shaped pieces of gypsum. (Author)

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.

Factorial Study of Compressive Mechanical Properties and Primary In Vitro Osteoblast Response of PHBV/PLLA Scaffolds

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Naznin Sultana

2012-01-01

Full Text Available For bone tissue regeneration, composite scaffolds containing biodegradable polymers and nanosized osteoconductive bioceramics have been regarded as promising biomimetic systems. Polymer blends of poly(hydroxybutyrate-co-hydroxyvalerate (PHBV and poly(L-lactic acid (PLLA can be used as the polymer matrix to control the degradation rate. In order to render the scaffolds osteoconductive, nano-sized hydroxyapatite (nHA particles can be incorporated into the polymer matrix. In the first part of this study, a factorial design approach to investigate the influence of materials on the initial compressive mechanical properties of the scaffolds was studied. In the second part, the protein adsorption behavior and the attachment and morphology of osteoblast-like cells (Saos-2 of the scaffolds in vitro were also studied. It was observed that nHA incorporated PHBV/PLLA composite scaffolds adsorbed more bovine serum albumin (BSA protein than PHBV or PHBV/PLLA scaffolds. In vitro studies also revealed that the attachment of human osteoblastic cells (SaOS-2 was significantly higher in nHA incorporated PHBV/PLLA composite scaffolds. From the SEM micrographs of nHA incorporated PHBV/PLLA composite scaffolds seeded with SaOS-2 cells after a 7-day cell culture period, it was observed that the cells were well expanded and spread in all directions on the scaffolds.

Students' Perceptions of a Scaffolded Approach to Learning Financial Planning: An Empirical Study

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Cull, Michelle; Davis, Glenda

2013-01-01

In the aftermath of the global financial crisis (GFC), one understandable area of scrutiny and pressure for reform is the educational background and professionalism of personal financial advisers. This Australian study reports on a three-year investigation into students' perceptions of "scaffolded" instruction in financial planning. The…

A study on improving mechanical properties of porous HA tissue engineering scaffolds by hot isostatic pressing

International Nuclear Information System (INIS)

Zhao Jing; Xiao Suguang; Lu Xiong; Wang Jianxin; Weng Jie

2006-01-01

Various interconnected porous hydroxyapatite (HA) ceramic scaffolds are universally used to induct the tissue growth for bone repair and replacement, and serve to support the adhesion, transfer, proliferation and differentiation of cells. Impregnation of polyurethane sponges with a ceramic slurry is adopted to produce highly porous HA ceramic scaffolds with a 3D interconnected structure. However, high porosity always accompanies a decrease in the strength of the HA ceramic scaffolds. Therefore, it is significant to improve the strength of the HA ceramic scaffolds with highly interconnected porosity so that they are more suitable in clinical applications. In this work, highly porous HA ceramic scaffolds are first produced by the polymer impregnation approach, and subsequently further sintered by hot isostatic pressing (HIP). The phase composition, macro- and micro-porous structure, sintering and mechanical properties of the porous HA scaffolds are investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM), nanoindentation analysis and compressive test. The experimental results show that the nanohardness and compressive strength of HIP-sintered porous HA ceramics are higher than those of commonly sintered HA scaffolds. The HIP technique can effectively improve the sintering property and densification of porous HA ceramic scaffolds, so inducing an increase in the compression strength

Scaffolding for Second Language Writers: Producing an Academic Essay.

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Cotterall, Sara; Cohen, Robin

2003-01-01

Describes how a group of intermediate learners of English were guided through the process of producing their first academic essays in English. The approach applied the concept of scaffolding to the academic writing process by proving flexible support for the learners throughout the writing of their essays. (Author/VWL)

Chiral Analysis of Pesticides and Drugs of Environmental Concern: Biodegradation and Enantiomeric Fraction

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Alexandra S. Maia

2017-09-01

Full Text Available The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF. The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.

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.

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

Development of nanocellulose scaffolds with tunable structures to support 3D cell culture.

Science.gov (United States)

Liu, Jun; Cheng, Fang; Grénman, Henrik; Spoljaric, Steven; Seppälä, Jukka; E Eriksson, John; Willför, Stefan; Xu, Chunlin

2016-09-05

Swollen three-dimensional nanocellulose films and their resultant aerogels were prepared as scaffolds towards tissue engineering application. The nanocellulose hydrogels with various swelling degree (up to 500 times) and the resultant aerogels with desired porosity (porosity up to 99.7% and specific surface area up to 308m(2)/g) were prepared by tuning the nanocellulose charge density, the swelling media conditions, and the material processing approach. Representative cell-based assays were applied to assess the material biocompatibility and efficacy of the human extracellular matrix (ECM)-mimicking nanocellulose scaffolds. The effects of charge density and porosity of the scaffolds on the biological tests were investigated for the first time. The results reveal that the nanocellulose scaffolds could promote the survival and proliferation of tumor cells, and enhance the transfection of exogenous DNA into the cells. These results suggest the usefulness of the nanocellulose-based matrices in supporting crucial cellular processes during cell growth and proliferation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Single molecule sequencing-guided scaffolding and correction of draft assemblies.

Science.gov (United States)

Zhu, Shenglong; Chen, Danny Z; Emrich, Scott J

2017-12-06

Although single molecule sequencing is still improving, the lengths of the generated sequences are inevitably an advantage in genome assembly. Prior work that utilizes long reads to conduct genome assembly has mostly focused on correcting sequencing errors and improving contiguity of de novo assemblies. We propose a disassembling-reassembling approach for both correcting structural errors in the draft assembly and scaffolding a target assembly based on error-corrected single molecule sequences. To achieve this goal, we formulate a maximum alternating path cover problem. We prove that this problem is NP-hard, and solve it by a 2-approximation algorithm. Our experimental results show that our approach can improve the structural correctness of target assemblies in the cost of some contiguity, even with smaller amounts of long reads. In addition, our reassembling process can also serve as a competitive scaffolder relative to well-established assembly benchmarks.

Highly porous scaffolds of PEDOT:PSS for bone tissue engineering.

Science.gov (United States)

Guex, Anne Géraldine; Puetzer, Jennifer L; Armgarth, Astrid; Littmann, Elena; Stavrinidou, Eleni; Giannelis, Emmanuel P; Malliaras, George G; Stevens, Molly M

2017-10-15

Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6±5.9µm and a total pore surface area of 7.72±1.7m 2 ·g -1 . The electrical conductivity, based on I-V curves, was measured to be 140µS·cm -1 with a reduced, but stable conductivity of 6.1µS·cm -1 after 28days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold

Microporous polymeric 3D scaffolds templated by the layer-by-layer self-assembly.

Science.gov (United States)

Paulraj, Thomas; Feoktistova, Natalia; Velk, Natalia; Uhlig, Katja; Duschl, Claus; Volodkin, Dmitry

2014-08-01

Polymeric scaffolds serve as valuable supports for biological cells since they offer essential features for guiding cellular organization and tissue development. The main challenges for scaffold fabrication are i) to tune an internal structure and ii) to load bio-molecules such as growth factors and control their local concentration and distribution. Here, a new approach for the design of hollow polymeric scaffolds using porous CaCO3 particles (cores) as templates is presented. The cores packed into a microfluidic channel are coated with polymers employing the layer-by-layer (LbL) technique. Subsequent core elimination at mild conditions results in formation of the scaffold composed of interconnected hollow polymer microspheres. The size of the cores determines the feature dimensions and, as a consequence, governs cellular adhesion: for 3T3 fibroblasts an optimal microsphere size is 12 μm. By making use of the carrier properties of the porous CaCO3 cores, the microspheres are loaded with BSA as a model protein. The scaffolds developed here may also be well suited for the localized release of bio-molecules using external triggers such as IR-light. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Reversed-Phase UHPLC Enantiomeric Separation of Rasagiline Salts Using a Chiralpak® AGP Column

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Nagarajan Balaji

2017-07-01

Full Text Available We report the first rapid ultra-high performance liquid chromatographic (UHPLC enantiomeric reversed-phase separation of rasagiline mesylate and its tartrate salts using a Chiralpak® AGP column (50 mm × 2.1 mm, 5 μm as a stationary phase. This method was developed as an alternative to the usage of previously reported normal-phase chiral LC columns for isomer separation. Our method is based on an isocratic approach using a mixture of ammonium acetate and isopropyl alcohol (90:10, v/v as the mobile phase (0.6 mL/min flow rate. The detection limit (at a detection wavelength of 210 nm and quantification limit for the rasagiline enantiomers were 0.06 and 0.2 μg/mL, respectively. This method is compatible with the UHPLC-MS technique. The successful separation of rasagiline and its enantiomer was confirmed by determining the corresponding specific optical rotation values. Our method will be applicable for detecting rasagiline enantiomers during the control of manufacturing processes, and for use in rapid analysis for quality control in pharmaceutical industry to obtain optically pure pharmaceutical substances. This method was validated in terms of its precision, limit of detection, limit of quantification, linearity, accuracy, robustness, ruggedness, specificity, forced degradation, and solution stability, according to International Council on Harmonization Validation Guidelines Q2 (R1.

Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions.

Science.gov (United States)

Mitra, Tapas; Sailakshmi, G; Gnanamani, A; Mandal, A B

2012-05-01

The present study emphasizes the influence of non-covalent interactions on the mechanical and thermal properties of the scaffolds of chitosan/collagen origin. Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross-linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v) and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile strength, stiffness, Young's modulus, etc.) assessment demonstrated the existence of non-covalent interaction between MA and chitosan/collagen, which offered flexibility and high strength to the scaffolds suitable for tissue engineering research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility nature of the scaffolds. Docking simulation study further supports the intermolecular hydrogen bonding interactions between MA and chitosan/collagen.

Design and characterization of a biodegradable composite scaffold for ligament tissue engineering.

Science.gov (United States)

Hayami, James W S; Surrao, Denver C; Waldman, Stephen D; Amsden, Brian G

2010-03-15

Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the ligament. The composite scaffold was constructed from cell-adherent, base-etched, electrospun poly(epsilon-caprolactone-co-D,L-lactide) (PCLDLLA) fibers embedded in a noncell-adherent photocrosslinked N-methacrylated glycol chitosan (MGC) hydrogel seeded with primary ligament fibroblasts. Base etching improved cellular adhesion to the PCLDLLA material. Cells within the MGC hydrogel remained viable (72 +/- 4%) during the 4-week culture period. Immunohistochemistry staining revealed ligament ECM markers collagen type I, collagen type III, and decorin organizing and accumulating along the PCLDLLA fibers within the composite scaffolds. On the basis of these results, it was determined that the composite scaffold design was a viable alternative to the current approaches used for ligament tissue engineering and merits further study. (c) 2009 Wiley Periodicals, Inc.

Optimal elastomeric scaffold leaflet shape for pulmonary heart valve leaflet replacement.

Science.gov (United States)

Fan, Rong; Bayoumi, Ahmed S; Chen, Peter; Hobson, Christopher M; Wagner, William R; Mayer, John E; Sacks, Michael S

2013-02-22

Surgical replacement of the pulmonary valve (PV) is a common treatment option for congenital pulmonary valve defects. Engineered tissue approaches to develop novel PV replacements are intrinsically complex, and will require methodical approaches for their development. Single leaflet replacement utilizing an ovine model is an attractive approach in that candidate materials can be evaluated under valve level stresses in blood contact without the confounding effects of a particular valve design. In the present study an approach for optimal leaflet shape design based on finite element (FE) simulation of a mechanically anisotropic, elastomeric scaffold for PV replacement is presented. The scaffold was modeled as an orthotropic hyperelastic material using a generalized Fung-type constitutive model. The optimal shape of the fully loaded PV replacement leaflet was systematically determined by minimizing the difference between the deformed shape obtained from FE simulation and an ex-vivo microCT scan of a native ovine PV leaflet. Effects of material anisotropy, dimensional changes of PV root, and fiber orientation on the resulting leaflet deformation were investigated. In-situ validation demonstrated that the approach could guide the design of the leaflet shape for PV replacement surgery. Copyright © 2012 Elsevier Ltd. All rights reserved.

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)

In vitro characterization of 3D printed scaffolds aimed at bone tissue regeneration.

Science.gov (United States)

Boga, João C; Miguel, Sónia P; de Melo-Diogo, Duarte; Mendonça, António G; Louro, Ricardo O; Correia, Ilídio J

2018-05-01

The incidence of fractures and bone-related diseases like osteoporosis has been increasing due to aging of the world's population. Up to now, grafts and titanium implants have been the principal therapeutic approaches used for bone repair/regeneration. However, these types of treatment have several shortcomings, like limited availability, risk of donor-to-recipient infection and tissue morbidity. To overcome these handicaps, new 3D templates, capable of replicating the features of the native tissue, are currently being developed by researchers from the area of tissue engineering. These 3D constructs are able to provide a temporary matrix on which host cells can adhere, proliferate and differentiate. Herein, 3D cylindrical scaffolds were designed to mimic the natural architecture of hollow bones, and to allow nutrient exchange and bone neovascularization. 3D scaffolds were produced with tricalcium phosphate (TCP)/alginic acid (AA) using a Fab@home 3D printer. Furthermore, graphene oxide (GO) was incorporated into the structure of some scaffolds to further enhance their mechanical properties. The results revealed that the scaffolds incorporating GO displayed greater porosity, without impairing their mechanical properties. These scaffolds also presented a controlled swelling profile, enhanced biomineralization capacity and were able to increase the Alkaline Phosphatase (ALP) activity. Such characteristics make TCP/AA scaffolds functionalized with GO promising 3D constructs for bone tissue engineering applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Composite microsphere-functionalized scaffold for the controlled release of small molecules in tissue engineering

Directory of Open Access Journals (Sweden)

Laura Pandolfi

2016-01-01

Full Text Available Current tissue engineering strategies focus on restoring damaged tissue architectures using biologically active scaffolds. The ideal scaffold would mimic the extracellular matrix of any tissue of interest, promoting cell proliferation and de novo extracellular matrix deposition. A plethora of techniques have been evaluated to engineer scaffolds for the controlled and targeted release of bioactive molecules to provide a functional structure for tissue growth and remodeling, as well as enhance recruitment and proliferation of autologous cells within the implant. Recently, novel approaches using small molecules, instead of growth factors, have been exploited to regulate tissue regeneration. The use of small synthetic molecules could be very advantageous because of their stability, tunability, and low cost. Herein, we propose a chitosan–gelatin scaffold functionalized with composite microspheres consisting of mesoporous silicon microparticles and poly(dl-lactic-co-glycolic acid for the controlled release of sphingosine-1-phospate, a small molecule of interest. We characterized the platform with scanning electron microscopy, Fourier transform infrared spectroscopy, and confocal microscopy. Finally, the biocompatibility of this multiscale system was analyzed by culturing human mesenchymal stem cells onto the scaffold. The presented strategy establishes the basis of a versatile scaffold for the controlled release of small molecules and for culturing mesenchymal stem cells for regenerative medicine applications.

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.

Effect of pore architecture and stacking direction on mechanical properties of solid freeform fabrication-based scaffold for bone tissue engineering.

Science.gov (United States)

Lee, Jung-Seob; Cha, Hwang Do; Shim, Jin-Hyung; Jung, Jin Woo; Kim, Jong Young; Cho, Dong-Woo

2012-07-01

Fabrication of a three-dimensional (3D) scaffold with increased mechanical strength may be an essential requirement for more advanced bone tissue engineering scaffolds. Various material- and chemical-based approaches have been explored to enhance the mechanical properties of engineered bone tissue scaffolds. In this study, the effects of pore architecture and stacking direction on the mechanical and cell proliferation properties of a scaffold were investigated. The 3D scaffold was prepared using solid freeform fabrication technology with a multihead deposition system. Various types of scaffolds with different pore architectures (lattice, stagger, and triangle types) and stacking directions (horizontal and vertical directions) were fabricated with a blend of polycaprolactone and poly lactic-co-glycolic acid. In compression tests, the triangle-type scaffold was the strongest among the experimental groups. Stacking direction affected the mechanical properties of scaffolds. An in vitro cell counting kit-8 assay showed no significant differences in optical density depending on the different pore architectures and stacking directions. In conclusion, mechanical properties of scaffolds can be enhanced by controlling pore architecture and stacking direction. Copyright © 2012 Wiley Periodicals, Inc.

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.

Development of Chiral LC-MS Methods for small Molecules and Their Applications in the Analysis of Enantiomeric Composition and Pharmacokinetic Studies

Energy Technology Data Exchange (ETDEWEB)

Desai, Meera Jay [Iowa State Univ., Ames, IA (United States)

2004-01-01

The purpose of this research was to develop sensitive LC-MS methods for enantiomeric separation and detection, and then apply these methods for determination of enantiomeric composition and for the study of pharmacokinetic and pharmacodynamic properties of a chiral nutraceutical. Our first study, evaluated the use of reverse phase and polar organic mode for chiral LC-API/MS method development. Reverse phase methods containing high water were found to decrease ionization efficiency in electrospray, while polar organic methods offered good compatibility and low limits of detection with ESI. The use of lower flow rates dramatically increased the sensitivity by an order of magnitude. Additionally, for rapid chiral screening, the coupled Chirobiotic column afforded great applicability for LC-MS method development. Our second study, continued with chiral LC-MS method development in this case for the normal phase mode. Ethoxynonafluorobutane, a fluorocarbon with low flammability and no flashpoint, was used as a substitute solvent for hexane/heptane mobile phases for LC-APCI/MS. Comparable chromatographic resolutions and selectivities were found using ENFB substituted mobile phase systems, although, peak efficiencies were significantly diminished. Limits of detection were either comparable or better for ENFB-MS over heptane-PDA detection. The miscibility of ENFB with a variety of commonly used organic modifiers provided for flexibility in method development. For APCI, lower flow rates did not increase sensitivity as significantly as was previously found for ESI-MS detection. The chiral analysis of native amino acids was evaluated using both APCI and ESI sources. For free amino acids and small peptides, APCI was found to have better sensitivities over ESI at high flow rates. For larger peptides, however, sensitivity was greatly improved with the use of electrospray. Additionally, sensitivity was enhanced with the use of non-volatile additives, This optimized method was then

Evaluation of early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffold. An experimental study in Wistar rats.

LENUS (Irish Health Repository)

Alhag, Mohamed

2011-03-01

Tissue engineering using cell-seeded biodegradable scaffolds offers a new bone regenerative approach that might circumvent many of the limitations of current therapeutic modalities. The aim of this experiment was to study the early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffolds.

Mimicked cartilage scaffolds of silk fibroin/hyaluronic acid with stem cells for osteoarthritis surgery: Morphological, mechanical, and physical clues

International Nuclear Information System (INIS)

Jaipaew, Jirayut; Wangkulangkul, Piyanun; Meesane, Jirut; Raungrut, Pritsana; Puttawibul, Puttisak

2016-01-01

Osteoarthritis is a critical disease that comes from degeneration of cartilage tissue. In severe cases surgery is generally required. Tissue engineering using scaffolds with stem cell transplantation is an attractive approach and a challenge for orthopedic surgery. For sample preparation, silk fibroin (SF)/hyaluronic acid (HA) scaffolds in different ratios of SF/HA (w/w) (i.e., 100:0, 90:10, 80:20, and 70:30) were formed by freeze-drying. The morphological, mechanical, and physical clues were considered in this research. The morphological structure of the scaffolds was observed by scanning electron microscope. The mechanical and physical properties of the scaffolds were analyzed by compressive and swelling ratio testing, respectively. For the cell experiments, scaffolds were seeded and cultured with human umbilical cord-derived mesenchymal stem cells (HUMSCs). The cultured scaffolds were tested for cell viability, histochemistry, immunohistochemistry, and gene expression. The SF with HA scaffolds showed regular porous structures. Those scaffolds had a soft and elastic characteristic with a high swelling ratio and water uptake. The SF/HA scaffolds showed a spheroid structure of the cells in the porous structure particularly in the SF80 and SF70 scaffolds. Cells could express Col2a, Agg, and Sox9 which are markers for chondrogenesis. It could be deduced that SF/HA scaffolds showed significant clues for suitability in cartilage tissue engineering and in surgery for osteoarthritis. - Highlights: • Silk fibroin/Hyaluronic acid was fabricated into mimicked scaffolds. • Mimicked scaffolds were incorporated with stem cells for chondrogenesis. • Mimicked scaffolds showed the clues for chondrogenic regulation. • Mimicked scaffolds had suitable performance for cartilage tissue engineering • Mimicked scaffolds showed promise for osteoarthritis surgery.

Mimicked cartilage scaffolds of silk fibroin/hyaluronic acid with stem cells for osteoarthritis surgery: Morphological, mechanical, and physical clues

Energy Technology Data Exchange (ETDEWEB)

Jaipaew, Jirayut [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Wangkulangkul, Piyanun [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Department of Surgery, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Meesane, Jirut, E-mail: jirutmeesane999@yahoo.co.uk [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Raungrut, Pritsana [Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Puttawibul, Puttisak [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Department of Surgery, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand)

2016-07-01

Osteoarthritis is a critical disease that comes from degeneration of cartilage tissue. In severe cases surgery is generally required. Tissue engineering using scaffolds with stem cell transplantation is an attractive approach and a challenge for orthopedic surgery. For sample preparation, silk fibroin (SF)/hyaluronic acid (HA) scaffolds in different ratios of SF/HA (w/w) (i.e., 100:0, 90:10, 80:20, and 70:30) were formed by freeze-drying. The morphological, mechanical, and physical clues were considered in this research. The morphological structure of the scaffolds was observed by scanning electron microscope. The mechanical and physical properties of the scaffolds were analyzed by compressive and swelling ratio testing, respectively. For the cell experiments, scaffolds were seeded and cultured with human umbilical cord-derived mesenchymal stem cells (HUMSCs). The cultured scaffolds were tested for cell viability, histochemistry, immunohistochemistry, and gene expression. The SF with HA scaffolds showed regular porous structures. Those scaffolds had a soft and elastic characteristic with a high swelling ratio and water uptake. The SF/HA scaffolds showed a spheroid structure of the cells in the porous structure particularly in the SF80 and SF70 scaffolds. Cells could express Col2a, Agg, and Sox9 which are markers for chondrogenesis. It could be deduced that SF/HA scaffolds showed significant clues for suitability in cartilage tissue engineering and in surgery for osteoarthritis. - Highlights: • Silk fibroin/Hyaluronic acid was fabricated into mimicked scaffolds. • Mimicked scaffolds were incorporated with stem cells for chondrogenesis. • Mimicked scaffolds showed the clues for chondrogenic regulation. • Mimicked scaffolds had suitable performance for cartilage tissue engineering • Mimicked scaffolds showed promise for osteoarthritis surgery.

Mag-seeding of rat bone marrow stromal cells into porous hydroxyapatite scaffolds for bone tissue engineering.

Science.gov (United States)

Shimizu, Kazunori; Ito, Akira; Honda, Hiroyuki

2007-09-01

Bone tissue engineering has been investigated as an alternative strategy for autograft transplantation. In the process of tissue engineering, cell seeding into three-dimensional (3-D) scaffolds is the first step for constructing 3-D tissues. We have proposed a methodology of cell seeding into 3-D porous scaffolds using magnetic force and magnetite nanoparticles, which we term Mag-seeding. In this study, we applied this Mag-seeding technique to bone tissue engineering using bone marrow stromal cells (BMSCs) and 3-D hydroxyapatite (HA) scaffolds. BMSCs were magnetically labeled with our original magnetite cationic liposomes (MCLs) having a positive surface charge to improve adsorption to cell surface. Magnetically labeled BMSCs were seeded onto a scaffold, and a 1-T magnet was placed under the scaffold. By using Mag-seeding, the cells were successfully seeded into the internal space of scaffolds with a high cell density. The cell seeding efficiency into HA scaffolds by Mag-seeding was approximately threefold larger than that by static-seeding (conventional method, without a magnet). After a 14-d cultivation period using the osteogenic induction medium by Mag-seeding, the level of two representative osteogenic markers (alkaline phosphatase and osteocalcin) were significantly higher than those by static-seeding. These results indicated that Mag-seeding of BMSCs into HA scaffolds is an effective approach to bone tissue engineering.

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.

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity.

Science.gov (United States)

Entekhabi, Elahe; Haghbin Nazarpak, Masoumeh; Moztarzadeh, Fathollah; Sadeghi, Ali

2016-12-01

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell-scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro study on the degradation of lithium-doped hydroxyapatite for bone tissue engineering scaffold

Energy Technology Data Exchange (ETDEWEB)

Wang, Yaping; Yang, Xu; Gu, Zhipeng; Qin, Huanhuan [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Li, Li [Department of Oncology, The 452 Hospital of Chinese PLA, Chengdu, Sichuan Province 610021 (China); Liu, Jingwang [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China); Yu, Xixun, E-mail: yuxixun@163.com [College of Polymer Science and Engineering, Sichuan University, Chengdu 610065 (China)

2016-09-01

Li-doped hydroxyapatite (LiHA) which is prepared through introducing low dose of Li into hydroxyapatite (HA) has been increasingly studied as a bone tissue-engineered scaffold. The degradation properties play a crucial role in the success of long-term implantation of a bone tissue-engineered construct. Herein, the in vitro degradation behaviors of LiHA scaffolds via two approaches were investigated in this study: solution-mediated degradation and osteoblast-mediated degradation. In solution-mediated degradation, after being immersed in simulated body fluid (SBF) for some time, some characteristics of these scaffolds (such as release of ionized lithium and phosphate, pH change, mechanical properties, cytocompatibility and SEM surface characterization) were systematically tested. A similar procedure was also employed to research the degradation behaviors of LiHA scaffolds in osteoblast-mediated degradation. The results suggested that the degradation in SBF and degradation in culture medium with cell existed distinguishing mechanisms. LiHA scaffolds were degraded via a hydrolytic mechanism when they were soaked in SBF. Upon degradation, an apatite precipitation (layer) was formed on the surfaces of scaffolds. While a biological mechanism was presented for the degradation of scaffolds in cell-mediated degradation. Compared with pure HA, LiHA scaffolds had a better effect on the growth of osteoblast cells, meanwhile, the release amount of PO{sub 4}{sup 3−} in a degradation medium indicated that osteoblasts could accelerate the degradation of LiHA due to the more physiological activities of osteoblast. According to the results from compressive strength test, doping Li into HA could enhance the strength of HA. Moreover, the results from MTT assay and SEM observation showed that the degradation products of LiHA scaffolds were beneficial to the proliferation of osteoblasts. The results of this research can provide the theoretical basis for the clinical application of Li

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

Science.gov (United States)

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

High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening.

Science.gov (United States)

Shcherbakova, Elena G; Brega, Valentina; Lynch, Vincent M; James, Tony D; Anzenbacher, Pavel

2017-07-26

A simple and efficient method for determination of the yield, enantiomeric/diasteriomeric excess (ee/de), and absolute configuration of crude chiral diols without the need of work-up and product isolation in a high throughput setting is described. This approach utilizes a self-assembled iminoboronate ester formed as a product by dynamic covalent self-assembly of a chiral diol with an enantiopure fluorescent amine such as tryptophan methyl ester or tryptophanol and 2-formylphenylboronic acid. The resulting diastereomeric boronates display different photophysical properties and allow for fluorescence-based ee determination of molecules containing a 1,2- or 1,3-diol moiety. This method has been utilized for the screening of ee in a number of chiral diols including atorvastatin, a statin used for the treatment of hypercholesterolemia. Noyori asymmetric hydrogenation of benzil was performed in a highly parallel fashion with errors products from the parallel asymmetric synthesis in real time and in a high-throughput screening (HTS) fashion. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

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

Energy Technology Data Exchange (ETDEWEB)

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

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.

In vivo guided vascular regeneration with a non-porous elastin-like polypeptide hydrogel tubular scaffold.

Science.gov (United States)

Mahara, Atsushi; Kiick, Kristi L; Yamaoka, Tetsuji

2017-06-01

Herein, we demonstrate a new approach for small-caliber vascular reconstruction using a non-porous elastin-like polypeptide hydrogel tubular scaffold, based on the concept of guided vascular regeneration (GVR). The scaffolds are composed of elastin-like polypeptide, (Val-Pro-Gly-Ile-Gly) n , for compliance matching and antithrombogenicity and an Arg-Gly-Asp (RGD) motif for connective tissue regeneration. When the polypeptide was mixed with an aqueous solution of β-[Tris(hydroxymethyl)phosphino]propionic acid at 37°C, the polypeptide hydrogel was rapidly formed. The elastic modulus of the hydrogel was 4.4 kPa. The hydrogel tubular scaffold was formed in a mold and reinforced with poly(lactic acid) nanofibers. When tubular scaffolds with an inner diameter of 1 mm and length of 5 mm were implanted into rat abdominal aortae, connective tissue grew along the scaffold luminal surface from the flanking native tissues, resulting in new blood vessel tissue with a thickness of 200 μm in 1 month. In contrast, rats implanted with control scaffolds without the RGD motif died. These results indicate that the non-porous hydrogel tubular scaffold containing the RGD motif effectively induced rapid tissue regeneration and that GVR is a promising strategy for the regeneration of small-diameter blood vessels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1746-1755, 2017. © 2017 Wiley Periodicals, Inc.

[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.

Fabrication and characterization of hydrothermal cross-linked chitosan porous scaffolds for cartilage tissue engineering applications.

Science.gov (United States)

Shamekhi, Mohammad Amin; Rabiee, Ahmad; Mirzadeh, Hamid; Mahdavi, Hamid; Mohebbi-Kalhori, Davod; Baghaban Eslaminejad, Mohamadreza

2017-11-01

The use of various chemical cross-linking agents for the improvement of scaffolds physical and mechanical properties is a common practical method, which is limited by cytotoxicity effects. Due to exerting contract type forces, chondrocytes are known to implement shrinkage on the tissue engineered constructs, which can be avoided by the scaffold cross-linking. In the this research, chitosan scaffolds are cross-linked with hydrothermal treatment with autoclave sterilization time of 0, 10, 20 and 30min, to avoid the application of the traditional chemical toxic materials. The optimization studies with gel content and crosslink density measurements indicate that for 20min sterilization time, the gel content approaches to ~80%. The scaffolds are fully characterized by the conventional techniques such as SEM, porosity and permeability, XRD, compression, thermal analysis and dynamic mechanical thermal analysis (DMTA). FT-IR studies shows that autoclave inter-chain cross-linking reduces the amine group absorption at 1560cm -1 and increase the absorption of N-acetylated groups at 1629cm -1 . It is anticipated, that this observation evidenced by chitosan scaffold browning upon autoclave cross-linking is an indication of the familiar maillard reaction between amine moieties and carbonyl groups. The biodegradation rate analysis shows that chitosan scaffolds with lower concentrations, possess suitable degradation rate for cartilage tissue engineering applications. In addition, cytotoxicity analysis shows that fabricated scaffolds are biocompatible. The human articular chondrocytes seeding into 3D cross-linked scaffolds shows a higher viability and proliferation in comparison with the uncross-linked samples and 2D controls. Investigation of cell morphology on the scaffolds by SEM, shows a more spherical morphology of chondrocytes on the cross-linked scaffolds for 21days of in vitro culture. Copyright © 2017. Published by Elsevier B.V.

Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

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Song, Min Jae; Dean, David; Knothe Tate, Melissa L

2013-07-01

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inverse Opal Scaffolds and Their Biomedical Applications.

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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.

Use of Clotted Human Plasma and Aprotinin in Skin Tissue Engineering: A Novel Approach to Engineering Composite Skin on a Porous Scaffold.

Science.gov (United States)

Paul, Michelle; Kaur, Pritinder; Herson, Marisa; Cheshire, Perdita; Cleland, Heather; Akbarzadeh, Shiva

2015-10-01

Tissue-engineered composite skin is a promising therapy for the treatment of chronic and acute wounds, including burns. Providing the wound bed with a dermal scaffold populated by autologous dermal and epidermal cellular components can further entice host cell infiltration and vascularization to achieve permanent wound closure in a single stage. However, the high porosity and the lack of a supportive basement membrane in most commercially available dermal scaffolds hinders organized keratinocyte proliferation and stratification in vitro and may delay re-epithelization in vivo. The objective of this study was to develop a method to enable the in vitro production of a human skin equivalent (HSE) that included a porous scaffold and dermal and epidermal cells expanded ex vivo, with the potential to be used for definitive treatment of skin defects in a single procedure. A collagen-glycosaminoglycan dermal scaffold (Integra(®)) was populated with adult fibroblasts. A near-normal skin architecture was achieved by the addition of coagulated human plasma to the fibroblast-populated scaffold before seeding cultured keratinocytes. This resulted in reducing scaffold pore size and improving contact surfaces. Skin architecture and basement membrane formation was further improved by the addition of aprotinin (a serine protease inhibitor) to the culture media to inhibit premature clot digestion. Histological assessment of the novel HSE revealed expression of keratin 14 and keratin 10 similar to native skin, with a multilayered neoepidermis morphologically comparable to human skin. Furthermore, deposition of collagen IV and laminin-511 were detected by immunofluorescence, indicating the formation of a continuous basement membrane at the dermal-epidermal junction. The proposed method was efficient in producing an in vitro near native HSE using the chosen off-the-shelf porous scaffold (Integra). The same principles and promising outcomes should be applicable to other biodegradable

In vivo bioluminescence imaging of cell differentiation in biomaterials: a platform for scaffold development.

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Bagó, Juli R; Aguilar, Elisabeth; Alieva, Maria; Soler-Botija, Carolina; Vila, Olaia F; Claros, Silvia; Andrades, José A; Becerra, José; Rubio, Nuria; Blanco, Jerónimo

2013-03-01

In vivo testing is a mandatory last step in scaffold development. Agile longitudinal noninvasive real-time monitoring of stem cell behavior in biomaterials implanted in live animals should facilitate the development of scaffolds for tissue engineering. We report on a noninvasive bioluminescence imaging (BLI) procedure for simultaneous monitoring of changes in the expression of multiple genes to evaluate scaffold performance in vivo. Adipose tissue-derived stromal mensenchymal cells were dually labeled with Renilla red fluorescent protein and firefly green fluorescent protein chimeric reporters regulated by cytomegalovirus and tissue-specific promoters, respectively. Labeled cells were induced to differentiate in vitro and in vivo, by seeding in demineralized bone matrices (DBMs) and monitored by BLI. Imaging results were validated by RT-polymerase chain reaction and histological procedures. The proposed approach improves molecular imaging and measurement of changes in gene expression of cells implanted in live animals. This procedure, applicable to the simultaneous analysis of multiple genes from cells seeded in DBMs, should facilitate engineering of scaffolds for tissue repair.

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.

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

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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.

Image-based quantification of fiber alignment within electrospun tissue engineering scaffolds is related to mechanical anisotropy.

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Fee, Timothy; Downs, Crawford; Eberhardt, Alan; Zhou, Yong; Berry, Joel

2016-07-01

It is well documented that electrospun tissue engineering scaffolds can be fabricated with variable degrees of fiber alignment to produce scaffolds with anisotropic mechanical properties. Several attempts have been made to quantify the degree of fiber alignment within an electrospun scaffold using image-based methods. However, these methods are limited by the inability to produce a quantitative measure of alignment that can be used to make comparisons across publications. Therefore, we have developed a new approach to quantifying the alignment present within a scaffold from scanning electron microscopic (SEM) images. The alignment is determined by using the Sobel approximation of the image gradient to determine the distribution of gradient angles with an image. This data was fit to a Von Mises distribution to find the dispersion parameter κ, which was used as a quantitative measure of fiber alignment. We fabricated four groups of electrospun polycaprolactone (PCL) + Gelatin scaffolds with alignments ranging from κ = 1.9 (aligned) to κ = 0.25 (random) and tested our alignment quantification method on these scaffolds. It was found that our alignment quantification method could distinguish between scaffolds of different alignments more accurately than two other published methods. Additionally, the alignment parameter κ was found to be a good predictor the mechanical anisotropy of our electrospun scaffolds. The ability to quantify fiber alignment within and make direct comparisons of scaffold fiber alignment across publications can reduce ambiguity between published results where cells are cultured on "highly aligned" fibrous scaffolds. This could have important implications for characterizing mechanics and cellular behavior on aligned tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1680-1686, 2016. © 2016 Wiley Periodicals, Inc.

Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus.

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Benjamin Mielich-Süss

2017-11-01

Full Text Available Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM, a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen.

Preparation of bioactive porous HA/PCL composite scaffolds

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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

Exploring the role of conceptual scaffolding in solving synthesis problems

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Lin Ding1,*

2011-10-01

Full Text Available It is well documented that when solving problems experts first search for underlying concepts while students tend to look for equations and previously worked examples. The overwhelming majority of end-of-chapter (EOC problems in most introductory physics textbooks contain only material and examples discussed in a single chapter, rarely requiring a solver to conduct a general search for underlying concepts. Hypothesizing that complete reliance on EOC problems trains students to rely on a nonexpert approach, we designed and implemented “synthesis” problems, each combining two major concepts that are broadly separated in the teaching timeline. To provide students with guided conceptual scaffolding, we encapsulated each synthesis problem into a sequence with two preceding conceptually based multiple-choice questions. Each question contained one of the major concepts covered in the subsequent synthesis problem. Results from a small-scale interview study and two large-scale written tests showed that the scaffolding encouraged students to search for and apply appropriate fundamental principles in solving synthesis problems, and that repeated training using scaffolded synthesis problems also helped students to make cross-topic transfers.

Laminin-Coated Poly(Methyl Methacrylate) (PMMA) Nanofiber Scaffold Facilitates the Enrichment of Skeletal Muscle Myoblast Population.

Science.gov (United States)

Zahari, Nor Kamalia; Idrus, Ruszymah Binti Haji; Chowdhury, Shiplu Roy

2017-10-30

Myoblasts, the contractile cells of skeletal muscle, have been invaluable for fundamental studies of muscle development and clinical applications for muscle loss. A major limitation to the myoblast-based therapeutic approach is contamination with non-contractile fibroblasts, which overgrow during cell expansion. To overcome these limitations, this study was carried out to establish a 3D culture environment using nanofiber scaffolds to enrich the myoblast population during construct formation. Poly(methyl methacrylate) (PMMA) nanofiber (PM) scaffolds were fabricated using electrospinning techniques and coated with extracellular matrix (ECM) proteins, such as collagen or laminin, in the presence or absence of genipin. A mixed population of myoblasts and fibroblasts was isolated from human skeletal muscle tissues and cultured on plain surfaces, as well as coated and non-coated PM scaffolds. PMMA can produce smooth fibers with an average diameter of 360 ± 50 nm. Adsorption of collagen and laminin on PM scaffolds is significantly enhanced in the presence of genipin, which introduces roughness to the nanofiber surface without affecting fiber diameter and mechanical properties. It was also demonstrated that laminin-coated PM scaffolds significantly enhance myoblast proliferation (0.0081 ± 0.0007 h -1 ) and migration (0.26 ± 0.04 μm/min), while collagen-coated PM scaffolds favors fibroblasts proliferation (0.0097 ± 0.0009 h -1 ) and migration (0.23 ± 0.03 μm/min). Consequently, the myoblast population was enriched on laminin-coated PM scaffolds throughout the culture process. Therefore, laminin coating of nanofiber scaffolds could be a potential scaffold for the development of a tissue-engineered muscle substitute.

Regeneration of musculoskeletal injuries using mesenchymal stem cells loaded scaffolds: review article

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Maryam Ataie

2017-07-01

Full Text Available An increase in the average age of the population and physical activities where the musculoskeletal system is involved as well as large number of people suffering from skeletal injuries which impose high costs on the society. Bone grafting is currently a standard clinical approach to treat or replace lost tissues. Autografts are the most common grafts, but they can lead to complications such as pain, infection, scarring and donor site morbidity. The alternative is allografts, but they also carry the risk of carrying infectious agents or immune rejection. Therefore, surgeons and researchers are looking for new therapeutic methods to improve bone tissue repair. The field of tissue engineering and the use of stem cells as an ideal cell source have emerged as a promising approach in recent years. Three main components in the field of tissue engineering include proper scaffolds, cells and growth factors that their combination leads to formation of tissue-engineered constructs, resulting in tissue repair and regeneration. The use of scaffolds with suitable properties could effectively improve the tissue function or even regenerate the damaged tissue. The main idea of tissue engineering is to design and fabricate an appropriate scaffold which can support cell attachment, proliferation, migration and differentiation to relevant tissue. Scaffold gives the tissue its structural and mechanical properties, for instance flexibility and stiffness that is related with the tissue functions. Biomaterials used to fabricate scaffolds can be categorized into natural or synthetic biodegradable or non-biodegradable materials. Polymers are the most widely used materials in tissue engineering. Growth factors are a group of proteins that cause cell proliferation and differentiation. Two main cell sources are specialized cells of desired tissue and stem cells. However, according to the low proliferation and limited accessibility to the cells of desired tissue, stem cells

Super-paramagnetic responsive silk fibroin/chitosan/magnetite scaffolds with tunable pore structures for bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Aliramaji, Shamsa; Zamanian, Ali, E-mail: a-zamanian@merc.ac.ir; Mozafari, Masoud

2017-01-01

Tissue engineering is a promising approach in repairing damaged tissues. During the last few years, magnetic nanoparticles have been of great interest in this field of study due to their controlled responsive characteristics in specific external magnetic fields. In this study, after synthesizing iron oxide (magnetite) nanoparticles through a reverse coprecipitation method, silk fibroin/chitosan-based magnetic scaffolds were prepared using different amounts of magnetite nanoparticles (0, 0.5, 1 and 2%) by freeze-casting method. The physicochemical activity of the scaffolds was monitored in phosphate-buffered saline (PBS) solution to determine the biodegradation and swelling behaviors. The stability of the magnetite nanoparticles in the fabricated scaffolds was determined by atomic absorption spectroscopy (AAS). Moreover, the cellular activity of the magnetic scaffolds was examined under a static magnetic field. The results showed that the lamellar structured scaffolds having MNPs in the walls could not affect the final structure and deteriorate the biological characteristics of the scaffolds, while the ability of magnetic responsivity was added to the scaffolds. This study warrants further pre-clinical and clinical evaluations. - Highlights: • Based on TEM micrograph and Rietveld refinement the particle size of MNPs was approximately 12 nm. • The water absorption of silk scaffolds increases by the addition of chitosan content. • Addition of 0.5 wt% MNPs led to decrease in scaffolds degradation and number of living cells. • By increasing the MNPs from 0.5 to 1 and 2, the degradation rate and living cells increased. • In scaffolds with 2 wt% MNPs cell attachment is slightly better than those of 0.5 wt%.

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity

International Nuclear Information System (INIS)

Entekhabi, Elahe; Haghbin Nazarpak, Masoumeh; Moztarzadeh, Fathollah; Sadeghi, Ali

2016-01-01

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell–scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. - Highlights: • This paper focuses on design a high porous nanofibrous scaffold. • Hyaluronic acid and polycaprolactone were used as materials to provide ideal conditions for nerve regeneration. • Proper physicochemical and mechanical signals applied for improving cell attachment

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity

Energy Technology Data Exchange (ETDEWEB)

Entekhabi, Elahe [Department of Biomedical Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 159163/4311 (Iran, Islamic Republic of); Haghbin Nazarpak, Masoumeh, E-mail: mhaghbinn@gmail.com [New Technologies Research Center (NTRC), Amirkabir University of Technology, Tehran 15875-4413 (Iran, Islamic Republic of); Moztarzadeh, Fathollah; Sadeghi, Ali [Department of Biomedical Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 159163/4311 (Iran, Islamic Republic of)

2016-12-01

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell–scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. - Highlights: • This paper focuses on design a high porous nanofibrous scaffold. • Hyaluronic acid and polycaprolactone were used as materials to provide ideal conditions for nerve regeneration. • Proper physicochemical and mechanical signals applied for improving cell attachment.

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

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.

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

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Stefan Bräse

2012-08-01

Full Text Available After prosperous domino reactions towards benzopyrans, the products were used as the starting material in Lewis acid catalyzed and organocatalytic Diels–Alder reactions to build up a tricyclic system. Herein, an asymmetric induction up to 96% enantiomeric excess was obtained by the use of imidazolidinone catalysts. This approach can be utilized to construct the tricyclic system in numerous natural products, in particular the scaffold of tetrahydrocannabinol (THC being the most representative one. Compared with other published methods, condensation with a preexisting cyclohexane moiety in the precursor is needed to gain the heterogenic tricycle systems, whereas we present a novel strategy towards cannabinoid derivatives based on a flexible modular synthesis.

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.

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.

Human amniotic epithelial cells combined with silk fibroin scaffold in the repair of spinal cord injury

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Ting-gang Wang

2016-01-01

Full Text Available Treatment and functional reconstruction after central nervous system injury is a major medical and social challenge. An increasing number of researchers are attempting to use neural stem cells combined with artificial scaffold materials, such as fibroin, for nerve repair. However, such approaches are challenged by ethical and practical issues. Amniotic tissue, a clinical waste product, is abundant, and amniotic epithelial cells are pluripotent, have low immunogenicity, and are not the subject of ethical debate. We hypothesized that amniotic epithelial cells combined with silk fibroin scaffolds would be conducive to the repair of spinal cord injury. To test this, we isolated and cultured amniotic epithelial cells, and constructed complexes of these cells and silk fibroin scaffolds. Implantation of the cell-scaffold complex into a rat model of spinal cord injury resulted in a smaller glial scar in the damaged cord tissue than in model rats that received a blank scaffold, or amniotic epithelial cells alone. In addition to a milder local immunological reaction, the rats showed less inflammatory cell infiltration at the transplant site, milder host-versus-graft reaction, and a marked improvement in motor function. These findings confirm that the transplantation of amniotic epithelial cells combined with silk fibroin scaffold can promote the repair of spinal cord injury. Silk fibroin scaffold can provide a good nerve regeneration microenvironment for amniotic epithelial cells.

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

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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.

Advanced computer-aided design for bone tissue-engineering scaffolds.

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Ramin, E; Harris, R A

2009-04-01

The design of scaffolds with an intricate and controlled internal structure represents a challenge for tissue engineering. Several scaffold-manufacturing techniques allow the creation of complex architectures but with little or no control over the main features of the channel network such as the size, shape, and interconnectivity of each individual channel, resulting in intricate but random structures. The combined use of computer-aided design (CAD) systems and layer-manufacturing techniques allows a high degree of control over these parameters with few limitations in terms of achievable complexity. However, the design of complex and intricate networks of channels required in CAD is extremely time-consuming since manually modelling hundreds of different geometrical elements, all with different parameters, may require several days to design individual scaffold structures. An automated design methodology is proposed by this research to overcome these limitations. This approach involves the investigation of novel software algorithms, which are able to interact with a conventional CAD program and permit the automated design of several geometrical elements, each with a different size and shape. In this work, the variability of the parameters required to define each geometry has been set as random, but any other distribution could have been adopted. This methodology has been used to design five cubic scaffolds with interconnected pore channels that range from 200 to 800 microm in diameter, each with an increased complexity of the internal geometrical arrangement. A clinical case study, consisting of an integration of one of these geometries with a craniofacial implant, is then presented.

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)

Molecular recognition and self-assembly special feature: A general protocol for creating high-throughput screening assays for reaction yield and enantiomeric excess applied to hydrobenzoin.

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Shabbir, Shagufta H; Regan, Clinton J; Anslyn, Eric V

2009-06-30

A general approach to high-throughput screening of enantiomeric excess (ee) and concentration was developed by using indicator displacement assays (IDAs), and the protocol was then applied to the vicinal diol hydrobenzoin. The method involves the sequential utilization of what we define herein as screening, training, and analysis plates. Several enantioselective boronic acid-based receptors were screened by using 96-well plates, both for their ability to discriminate the enantiomers of hydrobenzoin and to find their optimal pairing with indicators resulting in the largest optical responses. The best receptor/indicator combination was then used to train an artificial neural network to determine concentration and ee. To prove the practicality of the developed protocol, analysis plates were created containing true unknown samples of hydrobenzoin generated by established Sharpless asymmetric dihydroxylation reactions, and the best ligand was correctly identified.

Mesoporous Bioactive Glass Functionalized 3D Ti-6Al-4V Scaffolds with Improved Surface Bioactivity.

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Ye, Xiaotong; Leeflang, Sander; Wu, Chengtie; Chang, Jiang; Zhou, Jie; Huan, Zhiguang

2017-10-27

Porous Ti-6Al-4V scaffolds fabricated by means of selective laser melting (SLM), having controllable geometrical features and preferable mechanical properties, have been developed as a class of biomaterials that hold promising potential for bone repair. However, the inherent bio-inertness of the Ti-6Al-4V alloy as the matrix of the scaffolds results in a lack in the ability to stimulate bone ingrowth and regeneration. The aim of the present study was to develop a bioactive coating on the struts of SLM Ti-6Al-4V scaffolds in order to add the desired surface osteogenesis ability. Mesoporous bioactive glasses (MBGs) coating was applied on the strut surfaces of the SLM Ti-6Al-4V scaffolds through spin coating, followed by a heat treatment. It was found that the coating could maintain the characteristic mesoporous structure and chemical composition of MBG, and establish good interfacial adhesion to the Ti-6Al-4V substrate. The compressive strength and pore interconnectivity of the scaffolds were not affected by the coating. Moreover, the results obtained from in vitro cell culture experiments demonstrated that the attachment, proliferation, and differentiation of human bone marrow stromal cells (hBMSCs) on the MBG-coated Ti-6Al-4V scaffolds were improved as compared with those on the conventional bioactive glass (BG)-coated Ti-6Al-4V scaffolds and bare-metal Ti-6Al-4V scaffolds. Our results demonstrated that the MBG coating by using the spinning coating method could be an effective approach to achieving enhanced surface biofunctionalization for SLM Ti-6Al-4V scaffolds.

Laminin-Coated Poly(Methyl Methacrylate (PMMA Nanofiber Scaffold Facilitates the Enrichment of Skeletal Muscle Myoblast Population

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Nor Kamalia Zahari

2017-10-01

Full Text Available Myoblasts, the contractile cells of skeletal muscle, have been invaluable for fundamental studies of muscle development and clinical applications for muscle loss. A major limitation to the myoblast-based therapeutic approach is contamination with non-contractile fibroblasts, which overgrow during cell expansion. To overcome these limitations, this study was carried out to establish a 3D culture environment using nanofiber scaffolds to enrich the myoblast population during construct formation. Poly(methyl methacrylate (PMMA nanofiber (PM scaffolds were fabricated using electrospinning techniques and coated with extracellular matrix (ECM proteins, such as collagen or laminin, in the presence or absence of genipin. A mixed population of myoblasts and fibroblasts was isolated from human skeletal muscle tissues and cultured on plain surfaces, as well as coated and non-coated PM scaffolds. PMMA can produce smooth fibers with an average diameter of 360 ± 50 nm. Adsorption of collagen and laminin on PM scaffolds is significantly enhanced in the presence of genipin, which introduces roughness to the nanofiber surface without affecting fiber diameter and mechanical properties. It was also demonstrated that laminin-coated PM scaffolds significantly enhance myoblast proliferation (0.0081 ± 0.0007 h−1 and migration (0.26 ± 0.04 μm/min, while collagen-coated PM scaffolds favors fibroblasts proliferation (0.0097 ± 0.0009 h−1 and migration (0.23 ± 0.03 μm/min. Consequently, the myoblast population was enriched on laminin-coated PM scaffolds throughout the culture process. Therefore, laminin coating of nanofiber scaffolds could be a potential scaffold for the development of a tissue-engineered muscle substitute.

Mesoporous Bioactive Glass Functionalized 3D Ti-6Al-4V Scaffolds with Improved Surface Bioactivity

Directory of Open Access Journals (Sweden)

Xiaotong Ye

2017-10-01

Full Text Available Porous Ti-6Al-4V scaffolds fabricated by means of selective laser melting (SLM, having controllable geometrical features and preferable mechanical properties, have been developed as a class of biomaterials that hold promising potential for bone repair. However, the inherent bio-inertness of the Ti-6Al-4V alloy as the matrix of the scaffolds results in a lack in the ability to stimulate bone ingrowth and regeneration. The aim of the present study was to develop a bioactive coating on the struts of SLM Ti-6Al-4V scaffolds in order to add the desired surface osteogenesis ability. Mesoporous bioactive glasses (MBGs coating was applied on the strut surfaces of the SLM Ti-6Al-4V scaffolds through spin coating, followed by a heat treatment. It was found that the coating could maintain the characteristic mesoporous structure and chemical composition of MBG, and establish good interfacial adhesion to the Ti-6Al-4V substrate. The compressive strength and pore interconnectivity of the scaffolds were not affected by the coating. Moreover, the results obtained from in vitro cell culture experiments demonstrated that the attachment, proliferation, and differentiation of human bone marrow stromal cells (hBMSCs on the MBG-coated Ti-6Al-4V scaffolds were improved as compared with those on the conventional bioactive glass (BG-coated Ti-6Al-4V scaffolds and bare-metal Ti-6Al-4V scaffolds. Our results demonstrated that the MBG coating by using the spinning coating method could be an effective approach to achieving enhanced surface biofunctionalization for SLM Ti-6Al-4V scaffolds.

Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

Science.gov (United States)

Goh, Saik-Kia; Bertera, Suzanne; Olsen, Phillip; Candiello, Joe; Halfter, Willi; Uechi, Guy; Balasubramani, Manimalha; Johnson, Scott; Sicari, Brian; Kollar, Elizabeth; Badylak, Stephen F.; Banerjee, Ipsita

2013-01-01

Approximately 285 million people worldwide suffer from diabetes, with insulin supplementation as the most common treatment measure. Regenerative medicine approaches such as a bioengineered pancreas has been proposed as potential therapeutic alternatives. A bioengineered pancreas will benefit from the development of a bioscaffold that supports and enhances cellular function and tissue development. Perfusion-decellularized organs are a likely candidate for use in such scaffolds since they mimic compositional, architectural and biomechanical nature of a native organ. In this study, we investigate perfusion-decellularization of whole pancreas and the feasibility to recellularize the whole pancreas scaffold with pancreatic cell types. Our result demonstrates that perfusion-decellularization of whole pancreas effectively removes cellular and nuclear material while retaining intricate three-dimensional microarchitecture with perfusable vasculature and ductal network and crucial extracellular matrix (ECM) components. To mimic pancreatic cell composition, we recellularized the whole pancreas scaffold with acinar and beta cell lines and cultured up to 5 days. Our result shows successful cellular engraftment within the decellularized pancreas, and the resulting graft gave rise to strong up-regulation of insulin gene expression. These findings support biological utility of whole pancreas ECM as a biomaterials scaffold for supporting and enhancing pancreatic cell functionality and represent a step toward bioengineered pancreas using regenerative medicine approaches. PMID:23787110

[Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

Science.gov (United States)

Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

2016-03-01

To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

Fabrication of a reticular poly(lactide-co-glycolide) cylindrical scaffold for the in vitro development of microvascular networks

Science.gov (United States)

Tung, Yen-Ting; Chang, Cheng-Chung; Ju, Jyh-Cherng; Wang, Gou-Jen

2017-12-01

The microvascular network is a simple but critical system that is responsible for a range of important biological mechanisms in the bodies of all animals. The ability to generate a functional microvessel not only makes it possible to engineer vital tissue of considerable size but also serves as a platform for biomedical studies. However, most of the current methods for generating microvessel networks in vitro use rectangular channels which cannot represent real vessels in vivo and have dead zones at their corners, hence hindering the circulation of culture medium. We propose a scaffold-wrapping method which enables fabrication of a customized microvascular network in vitro in a more biomimetic way. By integrating microelectromechanical techniques with thermal reflow, we designed and fabricated a microscale hemi-cylindrical photoresist template. A replica mold of polydimethylsiloxane, produced by casting, was then used to generate cylindrical scaffolds with biodegradable poly(lactide-co-glycolide) (PLGA). Human umbilical vein endothelial cells were seeded on both sides of the PLGA scaffold and cultured using a traditional approach. The expression of endothelial cell marker CD31 and intercellular junction vascular endothelial cadherin on the cultured cell demonstrated the potential of generating a microvascular network with a degradable cylindrical scaffold. Our method allows cells to be cultured on a scaffold using a conventional culture approach and monitors cell conditions continuously. We hope our cell-covered scaffold can serve as a framework for building large tissues or can be used as the core of a vascular chip for in vitro circulation studies.

Ball with hair: modular functionalization of highly stable G-quadruplex DNA nano-scaffolds through N2-guanine modification.

Science.gov (United States)

Lech, Christopher Jacques; Phan, Anh Tuân

2017-06-20

Functionalized nanoparticles have seen valuable applications, particularly in the delivery of therapeutic and diagnostic agents in biological systems. However, the manufacturing of such nano-scale systems with the consistency required for biological application can be challenging, as variation in size and shape have large influences in nanoparticle behavior in vivo. We report on the development of a versatile nano-scaffold based on the modular functionalization of a DNA G-quadruplex. DNA sequences are functionalized in a modular fashion using well-established phosphoramidite chemical synthesis with nucleotides containing modification of the amino (N2) position of the guanine base. In physiological conditions, these sequences fold into well-defined G-quadruplex structures. The resulting DNA nano-scaffolds are thermally stable, consistent in size, and functionalized in a manner that allows for control over the density and relative orientation of functional chemistries on the nano-scaffold surface. Various chemistries including small modifications (N2-methyl-guanine), bulky aromatic modifications (N2-benzyl-guanine), and long chain-like modifications (N2-6-amino-hexyl-guanine) are tested and are found to be generally compatible with G-quadruplex formation. Furthermore, these modifications stabilize the G-quadruplex scaffold by 2.0-13.3 °C per modification in the melting temperature, with concurrent modifications producing extremely stable nano-scaffolds. We demonstrate the potential of this approach by functionalizing nano-scaffolds for use within the biotin-avidin conjugation approach. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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…

Development of a novel collagen-GAG nanofibrous scaffold via electrospinning

Energy Technology Data Exchange (ETDEWEB)

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

A review: fabrication of porous polyurethane scaffolds.

Science.gov (United States)

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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

Improved Syntheses and Expanded Analyses of the Enantiomerically Enriched Chiral Cobalt Complexes Co(en)[subscript 3]I[subscript 3] and Co(diNOsar)Br[subscript 3

Science.gov (United States)

McClellan, Michael J.; Cass, Marion E.

2015-01-01

This communication is a collection of additions and modifications to two previously published classic inorganic synthesis laboratory experiments. The experimental protocol for the synthesis and isolation of enantiomerically enriched ?- (or ?-)Co(en)[subscript 3]I[subscript 3] has been modified to increase reproducibility, yield, and enantiomeric…

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

Science.gov (United States)

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.

Examinations of a new long-term degradable electrospun polycaprolactone scaffold in three rat abdominal wall models

DEFF Research Database (Denmark)

Jangö, Hanna; Gräs, Søren; Christensen, Lise

2017-01-01

Alternative approaches to reinforce native tissue in reconstructive surgery for pelvic organ prolapse are warranted. Tissue engineering combines the use of a scaffold with the regenerative potential of stem cells and is a promising new concept in urogynecology. Our objective was to evaluate whether....... Properties of the new neo-tissue construct must be evaluated at the time of full degradation of the scaffold before its possible clinical value in pelvic organ prolapse surgery can be evaluated....... together, the long-term degradable polycaprolactone scaffold provided biomechanical reinforcement by inducing a marked foreign-body response and attracting numerous inflammatory cells to form a strong neo-tissue construct. However, cells from the muscle fiber fragments did not survive in this milieu...

A PEGylated platelet free plasma hydrogel based composite scaffold enables stable vascularization and targeted cell delivery for volumetric muscle loss.

Science.gov (United States)

Aurora, Amit; Wrice, Nicole; Walters, Thomas J; Christy, Robert J; Natesan, Shanmugasundaram

2018-01-01

Extracellular matrix (ECM) scaffolds are being used for the clinical repair of soft tissue injuries. Although improved functional outcomes have been reported, ECM scaffolds show limited tissue specific remodeling response with concomitant deposition of fibrotic tissue. One plausible explanation is the regression of blood vessels which may be limiting the diffusion of oxygen and nutrients across the scaffold. Herein we develop a composite scaffold as a vasculo-inductive platform by integrating PEGylated platelet free plasma (PFP) hydrogel with a muscle derived ECM scaffold (m-ECM). In vitro, adipose derived stem cells (ASCs) seeded onto the composite scaffold differentiated into two distinct morphologies, a tubular network in the hydrogel, and elongated structures along the m-ECM scaffold. The composite scaffold showed a high expression of ITGA5, ITGB1, and FN and a synergistic up-regulation of ang1 and tie-2 transcripts. The in vitro ability of the composite scaffold to provide extracellular milieu for cell adhesion and molecular cues to support vessel formation was investigated in a rodent volumetric muscle loss (VML) model. The composite scaffold delivered with ASCs supported robust and stable vascularization. Additionally, the composite scaffold supported increased localization of ASCs in the defect demonstrating its ability for localized cell delivery. Interestingly, ASCs were observed homing in the injured muscle and around the perivascular space possibly to stabilize the host vasculature. In conclusion, the composite scaffold delivered with ASCs presents a promising approach for scaffold vascularization. The versatile nature of the composite scaffold also makes it easily adaptable for the repair of soft tissue injuries. Decellularized extracellular matrix (ECM) scaffolds when used for soft tissue repair is often accompanied by deposition of fibrotic tissue possibly due to limited scaffold vascularization, which limits the diffusion of oxygen and nutrients

Towards 4D Printed Scaffolds for Tissue Engineering : Exploiting 3D Shape Memory Polymers to Deliver Time-Controlled Stimulus on Cultured Cells

NARCIS (Netherlands)

Hendrikson, Wilhelmus J.; Rouwkema, Jeroen; Clementi, Federico; van Blitterswijk, Clemens; Farè, Silvia; Moroni, Lorenzo

2017-01-01

Tissue engineering needs innovative solutions to better fit the requirements of a minimally invasive approach, providing at the same time instructive cues to cells. The use of shape memory polyurethane has been investigated by producing 4D scaffolds via additive manufacturing technology. Scaffolds

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

Energy Technology Data Exchange (ETDEWEB)

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.

Structure and conformational dynamics of scaffolded DNA origami nanoparticles

Science.gov (United States)

2017-05-08

vertices of the tetrahedron, and an unconstrained 4-arm vertex region corresponding to the vertices of the octahe- dron (Figure 2B and C). Both the 3...all-atommodels of the tetrahe- dron , octahedron, unconstrained 3- and 4-arm vertices, and the unconstrained duplex bulge represent equilibrium val...structural analysis of 4-arm vertices within a self-assembled octahe- dron imaged using cryo-EM (87). This prediction suggests an enantiomeric preference

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

Science.gov (United States)

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.

Science.gov (United States)

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

Science.gov (United States)

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.

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

Learning spaces as representational scaffolds for learning conceptual knowledge of system behaviour

NARCIS (Netherlands)

Bredeweg, B.; Liem, J.; Beek, W.; Salles, P.; Linnebank, F.; Wolpers, M.; Kirschner, P.A.; Scheffel, M.; Lindstaedt, S.; Dimitrova, V.

2010-01-01

Scaffolding is a well-known approach to bridge the gap between novice and expert capabilities in a discovery-oriented learning environment. This paper discusses a set of knowledge representations referred to as Learning Spaces (LSs) that can be used to support learners in acquiring conceptual

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

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.

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

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

Science.gov (United States)

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.

Development of a one-step approach for the reconstruction of full thickness skin defects using minced split thickness skin grafts and biodegradable synthetic scaffolds as a dermal substitute.

Science.gov (United States)

Sharma, Kavita; Bullock, Anthony; Ralston, David; MacNeil, Sheila

2014-08-01

Tissue engineering has progressed in delivering laboratory-expanded keratinocytes to the clinic; however the production of a suitable alternative to a skin graft, containing both epidermis and dermis still remains a challenge. To develop a one-step approach to wound reconstruction using finely minced split thickness skin and a biodegradable synthetic dermal substitute. This was explored in vitro using scalpel diced pieces of split thickness human skin combined with synthetic electrospun polylactide (PLA) scaffolds. To aid the spreading of tissue, 1% methylcellulose was used and platelet releasate was examined for its effect on cellular outgrowth from tissue explants. The outcome parameters included the metabolic activity of the migrating cells and their ability to produce collagen. Cell presence and migration on the scaffolds were assessed using fluorescence microscopy and SEM. Cells were identified as keratinocytes by immunostaining for pan-cytokeratin. Collagen deposition was quantified by using Sirius red. Skin cells migrated along the fibers of the scaffold and formed new collagen. 1% methylcellulose improved the tissue handling properties of the minced skin. Platelet releasate did not stimulate the migration of skin cells along scaffold fibers. Immunohistochemistry and SEM confirmed the presence of both epithelial and stromal cells in the new tissue. We describe the first key steps in the production of a skin substitute to be assembled in theatre eliminating the need for cell culture. Whilst further experiments are needed to develop this technique it can be a useful addition to armamentarium of the reconstructive surgeon. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

An anisotropically and heterogeneously aligned patterned electrospun scaffold with tailored mechanical property and improved bioactivity for vascular tissue engineering.

Science.gov (United States)

Xu, He; Li, Haiyan; Ke, Qinfei; Chang, Jiang

2015-04-29

The development of vascular scaffolds with controlled mechanical properties and stimulatory effects on biological activities of endothelial cells still remains a significant challenge to vascular tissue engineering. In this work, we reported an innovative approach to prepare a new type of vascular scaffolds with anisotropically and heterogeneously aligned patterns using electrospinning technique with unique wire spring templates, and further investigated the structural effects of the patterned electrospun scaffolds on mechanical properties and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs). Results showed that anisotropically aligned patterned nanofibrous structure was obtained by depositing nanofibers on template in a structurally different manner, one part of nanofibers densely deposited on the embossments of wire spring and formed cylindrical-like structures in the transverse direction, while others loosely suspended and aligned along the longitudinal direction, forming a three-dimensional porous microstructure. We further found that such structures could efficiently control the mechanical properties of electrospun vascular scaffolds in both longitudinal and transverse directions by altering the interval distances between the embossments of patterned scaffolds. When HUVECs were cultured on scaffolds with different microstructures, the patterned scaffolds distinctively promoted adhesion of HUVECs at early stage and proliferation during the culture period. Most importantly, cells experienced a large shape change associated with cell cytoskeleton and nuclei remodeling, leading to a stimulatory effect on angiogenesis differentiation of HUVECs by the patterned microstructures of electrospun scaffolds, and the scaffolds with larger distances of intervals showed a higher stimulatory effect. These results suggest that electrospun scaffolds with the anisotropically and heterogeneously aligned patterns, which could efficiently control the

Optimization of Polymer-ECM Composite Scaffolds for Tissue Engineering: Effect of Cells and Culture Conditions on Polymeric Nanofiber Mats

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Ritu Goyal

2017-01-01

Full Text Available The design of composite tissue scaffolds containing an extracellular matrix (ECM and synthetic polymer fibers is a new approach to create bioactive scaffolds that can enhance cell function. Currently, studies investigating the effects of ECM-deposition and decellularization on polymer degradation are still lacking, as are data on optimizing the stability of the ECM-containing composite scaffolds during prolonged cell culture. In this study, we develop fibrous scaffolds using three polymer compositions, representing slow (E0000, medium (E0500, and fast (E1000 degrading materials, to investigate the stability, degradation, and mechanics of the scaffolds during ECM deposition and decellularization, and during the complete cellularization-decell-recell cycle. We report data on percent molecular weight (% Mw retention of polymeric fiber mats, changes in scaffold stiffness, ECM deposition, and the presence of fibronectin after decellularization. We concluded that the fast degrading E1000 (Mw retention ≤ 50% after 28 days was not sufficiently stable to allow scaffold handling after 28 days in culture, while the slow degradation of E0000 (Mw retention ≥ 80% in 28 days did not allow deposited ECM to replace the polymer support. The scaffolds made from medium degrading E0500 (Mw retention about 60% at 28 days allowed the gradual replacement of the polymer network with cell-derived ECM while maintaining the polymer network support. Thus, polymers with an intermediate rate of degradation, maintaining good scaffold handling properties after 28 days in culture, seem best suited for creating ECM-polymer composite scaffolds.

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.

[Experimental study of tissue engineered cartilage construction using oriented scaffold combined with bone marrow mesenchymal stem cells in vivo].

Science.gov (United States)

Duan, Wei; Da, Hu; Wang, Wentao; Lü, Shangjun; Xiong, Zhuo; Liu, Jian

2013-05-01

matrix-derived scaffold can enhance the biomechanical property of tissue engineered cartilage and thus it represents a promising approach to cartilage tissue engineering.

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.

A new bi-layered scaffold for osteochondral tissue regeneration: In vitro and in vivo preclinical investigations

Energy Technology Data Exchange (ETDEWEB)

Sartori, M. [Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopedic Institute, Bologna (Italy); Pagani, S., E-mail: stefania.pagani@ior.it [Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna (Italy); Ferrari, A. [Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna (Italy); Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna (Italy); Costa, V.; Carina, V. [Innovative Technology Platform for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo (Italy); Figallo, E. [Fin-Ceramica Faenza SpA, Faenza, Ravenna (Italy); Maltarello, M.C. [Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna (Italy); Martini, L.; Fini, M. [Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna (Italy); Giavaresi, G. [Innovative Technology Platform for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo (Italy)

2017-01-01

Current treatments for acute or degenerative chondral and osteochondral lesions are in need of improvement, as these types of injuries lead to disability and worsen the quality of life in a high percentage of patients. The aim of this study was to develop a new bi-layered scaffold for osteochondral tissue regeneration through a “biomimetic” and “bioinspired” approach. For chondral regeneration, the scaffold was realized with an organic compound (type I collagen), while for the regeneration of the subchondral layer, bioactive magnesium-doped hydroxyapatite (Mg/HA) crystals were co-precipitated with the organic component of the scaffold. The entire scaffold structure was stabilized with a cross-linking agent, highly reactive bis-epoxyde (1,4-butanediol diglycidyl ether – BDDGE 1 wt%). The developed scaffold was then characterized for its physico-chemical characteristics. Its structure and adhesion strength between the integrated layers were investigated. At the same time, in vitro cell culture studies were carried out to examine the ability of chondral and bone scaffold layers to separately support adhesion, proliferation and differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes and osteoblasts, respectively. Moreover, an in vivo study with nude mice, transplanted with osteochondral scaffolds plain or engineered with undifferentiated hMSCs, was also set up with 4 and 8-week time points. The results showed that chondral and bone scaffold layers represented biocompatible scaffolds able to sustain hMSCs attachment and proliferation. Moreover, the association of scaffold stimuli and differentiation medium, induced hMSCs chondrogenic and osteogenic differentiation and deposition of extracellular matrix (ECM). The ectopic implantation of the engineered osteochondral scaffolds indicated that hMSCs were able to colonize the osteochondral scaffold in depth. The scaffold appeared permissive to tissue growth and penetration, ensuring the diffusion

Apatite nano-crystalline surface modification of poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering: implications for protein adsorption.

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Jabbarzadeh, Ehsan; Nair, Lakshmi S; Khan, Yusuf M; Deng, Meng; Laurencin, Cato T

2007-01-01

A number of bone tissue engineering approaches are aimed at (i) increasing the osteconductivity and osteoinductivity of matrices, and (ii) incorporating bioactive molecules within the scaffolds. In this study we examined the growth of a nano-crystalline mineral layer on poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for tissue engineering. In addition, the influence of the mineral precipitate layer on protein adsorption on the scaffolds was studied. Scaffolds were mineralized by incubation in simulated body fluid (SBF). Scanning electron microscopy (SEM) analysis revealed that mineralized scaffolds possess a rough surface with a plate-like nanostructure covering the surface of microspheres. The results of protein adsorption and release studies showed that while the protein release pattern was similar for PLAGA and mineralized PLAGA scaffolds, precipitation of the mineral layer on PLAGA led to enhanced protein adsorption and slower protein release. Mineralization of tissue-engineered surfaces provides a method for both imparting bioactivity and controlling levels of protein adsorption and release.

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...

Composition and Enantiomeric Analysis of the Essential Oil of the Fruits and the Leaves of Pistacia vera from Greece

OpenAIRE

Anastasia Tsokou; Katerina Georgopoulou; Eleni Melliou; Prokopios Magiatis; Eugenia Tsitsa

2007-01-01

The essential oils of the fruits and the leaves of pistachio (Pistacia vera L.) were analyzed by GC and GC/MS. Fresh unripe pistachio fruits were richer in essential oil (0.5 %, w/w) than the leaves (0.1 %, w/w). Twenty one compounds were identified in the essential oil of the fruits and the major components were (+)-α-pinene (54.6 %) and terpinolene (31.2 %). The enantiomeric ratio of the major constituents of the essential oil of the fruits was determined using chiral GC/MS and it was fo...

Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

Science.gov (United States)

Temple, Joshua P; Hutton, Daphne L; Hung, Ben P; Huri, Pinar Yilgor; Cook, Colin A; Kondragunta, Renu; Jia, Xiaofeng; Grayson, Warren L

2014-12-01

The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts. © 2014 Wiley Periodicals, Inc.

Morphology and characterization of 3D micro-porous structured chitosan scaffolds for tissue engineering.

Science.gov (United States)

Hsieh, Wen-Chuan; Chang, Chih-Pong; Lin, Shang-Ming

2007-06-15

This research studies the morphology and characterization of three-dimensional (3D) micro-porous structures produced from biodegradable chitosan for use as scaffolds for cells culture. The chitosan 3D micro-porous structures were produced by a simple liquid hardening method, which includes the processes of foaming by mechanical stirring without any chemical foaming agent added, and hardening by NaOH cross linking. The pore size and porosity were controlled with mechanical stirring strength. This study includes the morphology of chitosan scaffolds, the characterization of mechanical properties, water absorption properties and in vitro enzymatic degradation of the 3D micro-porous structures. The results show that chitosan 3D micro-porous structures were successfully produced. Better formation samples were obtained when chitosan concentration is at 1-3%, and concentration of NaOH is at 5%. Faster stirring rate would produce samples of smaller pore diameter, but when rotation speed reaches 4000 rpm and higher the changes in pore size is minimal. Water absorption would reduce along with the decrease of chitosan scaffolds' pore diameter. From stress-strain analysis, chitosan scaffolds' mechanical properties are improved when it has smaller pore diameter. From in vitro enzymatic degradation results, it shows that the disintegration rate of chitosan scaffolds would increase along with the processing time increase, but approaching equilibrium when the disintegration rate reaches about 20%.

Human Adipose-Derived Stem Cells on Rapid Prototyped Three-Dimensional Hydroxyapatite/Beta-Tricalcium Phosphate Scaffold.

Science.gov (United States)

Canciani, Elena; Dellavia, Claudia; Ferreira, Lorena Maria; Giannasi, Chiara; Carmagnola, Daniela; Carrassi, Antonio; Brini, Anna Teresa

2016-05-01

In the study, we assess a rapid prototyped scaffold composed of 30/70 hydroxyapatite (HA) and beta-tricalcium-phosphate (β-TCP) loaded with human adipose-derived stem cells (hASCs) to determine cell proliferation, differentiation toward osteogenic lineage, adhesion and penetration on/into the scaffold.In this in vitro study, hASCs isolated from fat tissue discarded after plastic surgery were expanded, characterized, and then loaded onto the scaffold. Cells were tested for: viability assay (Alamar Blue at days 3, 7 and Live/Dead at day 32), differentiation index (alkaline phosphatase activity at day 14), scaffold adhesion (standard error of the mean analysis at days 5 and 18), and penetration (ground sections at day 32).All the hASC populations displayed stemness markers and the ability to differentiate toward adipogenic and osteogenic lineages.Cellular vitality increased between 3 and 7 days, and no inhibitory effect by HA/β-TCP was observed. Under osteogenic stimuli, scaffold increased alkaline phosphatase activity of +243% compared with undifferentiated samples. Human adipose-derived stem cells adhered on HA/β-TCP surface through citoplasmatic extensions that occupied the macropores and built networks among them. Human adipose derived stem cells were observed in the core of HA/β-TCP. The current combination of hASCs and HA/β-TCP scaffold provided encouraging results. If authors' data will be confirmed in preclinical models, the present engineering approach could represent an interesting tool in treating large bone defects.

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

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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.

Iterative feedback bio-printing-derived cell-laden hydrogel scaffolds with optimal geometrical fidelity and cellular controllability.

Science.gov (United States)

Wang, Ling; Xu, Ming-En; Luo, Li; Zhou, Yongyong; Si, Peijian

2018-02-12

For three-dimensional bio-printed cell-laden hydrogel tissue constructs, the well-designed internal porous geometry is tailored to obtain the desired structural and cellular properties. However, significant differences often exist between the designed and as-printed scaffolds because of the inherent characteristics of hydrogels and cells. In this study, an iterative feedback bio-printing (IFBP) approach based on optical coherence tomography (OCT) for the fabrication of cell-laden hydrogel scaffolds with optimal geometrical fidelity and cellular controllability was proposed. A custom-made swept-source OCT (SS-OCT) system was applied to characterize the printed scaffolds quantitatively. Based on the obtained empirical linear formula from the first experimental feedback loop, we defined the most appropriate design constraints and optimized the printing process to improve the geometrical fidelity. The effectiveness of IFBP was verified from the second run using gelatin/alginate hydrogel scaffolds laden with C3A cells. The mismatch of the morphological parameters greatly decreased from 40% to within 7%, which significantly optimized the cell viability, proliferation, and morphology, as well as the representative expression of hepatocyte markers, including CYP3A4 and albumin, of the printed cell-laden hydrogel scaffolds. The demonstrated protocol paves the way for the mass fabrication of cell-laden hydrogel scaffolds, engineered tissues, and scaled-up applications of the 3D bio-printing technique.

Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects.

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Markus D Schofer

Full Text Available Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM.The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2 into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1 left unfilled, or treated with (2 bovine spongiosa, (3 PLLA scaffolds alone or (4 PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5.PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups.Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone

Improving PEEK bioactivity for craniofacial reconstruction using a 3D printed scaffold embedded with mesenchymal stem cells.

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Roskies, Michael; Jordan, Jack O; Fang, Dongdong; Abdallah, Mohamed-Nur; Hier, Michael P; Mlynarek, Alex; Tamimi, Faleh; Tran, Simon D

2016-07-01

Polyetheretherketone (PEEK) is a bioinert thermoplastic that has been investigated for its potential use in craniofacial reconstruction; however, its use in clinical practice is limited by a poor integration with adjacent bone upon implantation. To improve the bone-implant interface, two strategies have been employed: to modify its surface or to impregnate PEEK with bioactive materials. This study attempts to combine and improve upon the two approaches by modifying the internal structure into a trabecular network and to impregnate PEEK with mesenchymal stem cells. Furthermore, we compare the newly designed PEEK scaffolds' interactions with both bone-derived (BMSC) and adipose (ADSC) stem cells. Customized PEEK scaffolds were designed to incorporate a trabecular microstructure using a computer-aided design program and then printed via selective laser sintering (SLS), a 3D-printing process with exceptional accuracy. The scaffold structure was evaluated using microCT. Scanning electron microscopy (SEM) was used to evaluate scaffold morphology with and without mesenchymal stem cells (MSCs). Adipose and bone marrow mesenchymal cells were isolated from rats and cultured on scaffolds. Cell proliferation and differentiation were assessed using alamarBlue and alkaline phosphatase assays, respectively. Cell morphology after one week of co-culturing cells with PEEK scaffolds was evaluated using SEM. SLS 3D printing fabricated scaffolds with a porosity of 36.38% ± 6.66 and density of 1.309 g/cm(2). Cell morphology resembled viable fibroblasts attaching to the surface and micropores of the scaffold. PEEK scaffolds maintained the viability of both ADSCs and BMSCs; however, ADSCs demonstrated higher osteodifferentiation than BMSCs (p PEEK scaffolds that maintain the viability of adipose and bone marrow-derived MSCs and induce the osteodifferentiation of the adipose-derived MSCs. The combination of 3D printed PEEK scaffolds with MSCs could overcome some of the limitations

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

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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.

Alendronate-Eluting Biphasic Calcium Phosphate (BCP Scaffolds Stimulate Osteogenic Differentiation

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Sung Eun Kim

2015-01-01

Full Text Available Biphasic calcium phosphate (BCP scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN- eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM, energy-dispersive X-ray spectroscopy (EDS, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR. An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation.

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.

In vitro and in vivo evaluation of chitosan–gelatin scaffolds for cartilage tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Whu, Shu Wen [Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Hung, Kun-Che; Hsieh, Kuo-Huang [Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan (China); Chen, Chih-Hwa [Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Tsai, Ching-Lin, E-mail: tsaicl@ntuh.gov.tw [Department of Orthopaedics, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Shan-hui, E-mail: shhsu@ntu.edu.tw [Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan (China)

2013-07-01

Chitosan–gelatin polyelectrolyte complexes were fabricated and evaluated as tissue engineering scaffolds for cartilage regeneration in vitro and in vivo. The crosslinker for the gelatin component was selected among glutaraldehyde, bisepoxy, and a water-soluble carbodiimide (WSC) based upon the proliferation of chondrocytes on the crosslinked gelatin. WSC was found to be the most suitable crosslinker. Complex scaffolds made from chitosan and gelatin with a component ratio equal to one possessed the proper degradation rate and mechanical stability in vitro. Chondrocytes were able to proliferate well and secrete abundant extracellular matrix in the chitosan–gelatin (1:1) complex scaffolds crosslinked by WSC (C1G1{sub WSC}) compared to the non-crosslinked scaffolds. Implantation of chondrocytes-seeded scaffolds in the defects of rabbit articular cartilage confirmed that C1G1{sub WSC} promoted the cartilage regeneration. The neotissue formed the histological feature of tide line and lacunae in 6.5 months. The amount of glycosaminoglycans in C1G1{sub WSC} constructs (0.187 ± 0.095 μg/mg tissue) harvested from the animals after 6.5 months was 14 wt.% of that in normal cartilage (1.329 ± 0.660 μg/mg tissue). The average compressive modulus of regenerated tissue at 6.5 months was about 0.539 MPa, which approached to that of normal cartilage (0.735 MPa), while that in the blank control (3.881 MPa) was much higher and typical for fibrous tissue. Type II collagen expression in C1G1{sub WSC} constructs was similarly intense as that in the normal hyaline cartilage. According to the above results, the use of C1G1{sub WSC} scaffolds may enhance the cartilage regeneration in vitro and in vivo. - Highlights: • We developed a chitosan–gelatin scaffold crosslinked with carbodiimide. • Neocartilage formation was more evident in crosslinked vs. non-crosslinked scaffolds. • Histological features of tide line and lacunae were observed in vivo at 6.5 months. • Compressive

Production of new 3D scaffolds for bone tissue regeneration by rapid prototyping.

Science.gov (United States)

Fradique, R; Correia, T R; Miguel, S P; de Sá, K D; Figueira, D R; Mendonça, A G; Correia, I J

2016-04-01

The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration.

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.

Optimization strategies on the structural modeling of gelatin/chitosan scaffolds to mimic human meniscus tissue

International Nuclear Information System (INIS)

Sarem, Melika; Moztarzadeh, Fathollah; Mozafari, Masoud; Shastri, V. Prasad

2013-01-01

Meniscus lesions are frequently occurring injuries with poor ability to heal. Typical treatment procedure includes removal of damaged regions, which can lead to sub-optimal knee biomechanics and early onset of osteoarthritis. Some of the drawbacks of current treatment approach present an opportunity for a tissue engineering solution. In this study, gelatin (G)/chitosan (Cs) scaffolds were synthesized via gel casting method and cross-linked with naturally derived cross-linker, genipin, through scaffold cross-linking method. Based on the characteristics of native meniscus tissue microstructure and function, three different layers were chosen to design the macroporous multilayered scaffolds. The multi-layered scaffolds were investigated for their ability to support human-derived meniscus cells by evaluating their morphology and proliferation using MTT assay at various time points. Based on structural, mechanical and cell compatibility considerations, laminated scaffolds composed of G60/Cs40, G80/Cs20 and G40/Cs60 samples, for the first, second and third layers, respectively, could be an appropriate combination for meniscus tissue engineering applications. - Graphical abstract: The wedge shaped multilayer/multiporous G/Cs meniscus scaffolds were mimicked by MR images of anatomical knee meniscus. The layers were chosen as G60/Cs40, G80/Cs20 and G40/Cs60, according to their characteristics similar to meniscus natural tissue, as the first, second and third layers, respectively. - Highlights: • Different gelatin/chitosan systems were chosen to engineer a multilayered scaffold. • The compressive modulus increased gradually by increasing the gelatin concentration. • Further addition of gelatin showed a meaningful decrease in the water uptake degree. • The layers supported cell growth and mimicked the meniscus fibrocartilage structure

Optimization strategies on the structural modeling of gelatin/chitosan scaffolds to mimic human meniscus tissue

Energy Technology Data Exchange (ETDEWEB)

Sarem, Melika [Sports Engineering Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Institute for Macromolecular Chemistry, University of Freiburg, Hermann Staudinger Haus, Freiburg D-79104 (Germany); Helmholtz Virtual Institute: Multifunctional Biomaterials for Medicine, Freiburg (Germany); Moztarzadeh, Fathollah [Sports Engineering Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Mozafari, Masoud, E-mail: mozafari.masoud@gmail.com [Sports Engineering Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Helmerich Advanced Technology Research Center, School of Material Science and Engineering, Oklahoma State University, OK 74106 (United States); Shastri, V. Prasad [Institute for Macromolecular Chemistry, University of Freiburg, Hermann Staudinger Haus, Freiburg D-79104 (Germany); Helmholtz Virtual Institute: Multifunctional Biomaterials for Medicine, Freiburg (Germany)

2013-12-01

Meniscus lesions are frequently occurring injuries with poor ability to heal. Typical treatment procedure includes removal of damaged regions, which can lead to sub-optimal knee biomechanics and early onset of osteoarthritis. Some of the drawbacks of current treatment approach present an opportunity for a tissue engineering solution. In this study, gelatin (G)/chitosan (Cs) scaffolds were synthesized via gel casting method and cross-linked with naturally derived cross-linker, genipin, through scaffold cross-linking method. Based on the characteristics of native meniscus tissue microstructure and function, three different layers were chosen to design the macroporous multilayered scaffolds. The multi-layered scaffolds were investigated for their ability to support human-derived meniscus cells by evaluating their morphology and proliferation using MTT assay at various time points. Based on structural, mechanical and cell compatibility considerations, laminated scaffolds composed of G60/Cs40, G80/Cs20 and G40/Cs60 samples, for the first, second and third layers, respectively, could be an appropriate combination for meniscus tissue engineering applications. - Graphical abstract: The wedge shaped multilayer/multiporous G/Cs meniscus scaffolds were mimicked by MR images of anatomical knee meniscus. The layers were chosen as G60/Cs40, G80/Cs20 and G40/Cs60, according to their characteristics similar to meniscus natural tissue, as the first, second and third layers, respectively. - Highlights: • Different gelatin/chitosan systems were chosen to engineer a multilayered scaffold. • The compressive modulus increased gradually by increasing the gelatin concentration. • Further addition of gelatin showed a meaningful decrease in the water uptake degree. • The layers supported cell growth and mimicked the meniscus fibrocartilage structure.

Helix-helix inversion of an optically-inactive π-conjugated foldamer triggered by concentration changes of a single enantiomeric guest leading to a change in the helical stability.

Science.gov (United States)

Liu, Lijia; Ousaka, Naoki; Horie, Miki; Mamiya, Fumihiko; Yashima, Eiji

2016-09-27

A preferred-handed helicity induced in an optically-inactive poly(phenyleneethynylene)-based foldamer bearing carboxylic acid pendants upon complexation with a single enantiomeric diamine was subsequently inverted into the opposite helix upon further addition of the diamine, accompanied by a remarkable change in the stability of the helices.

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.

Rapid Prototyping Amphiphilic Polymer/Hydroxyapatite Composite Scaffolds with Hydration-Induced Self-Fixation Behavior

Science.gov (United States)

Kutikov, Artem B.; Gurijala, Anvesh

2015-01-01

the low-fouling 3D PELA inhibited the attachment of NIH3T3 fibroblasts or bone marrow stromal cells while the HA-PELA readily supported cellular attachment and osteogenic differentiation. Finally, we demonstrated the feasibility of rapid prototyping biphasic PELA/HA-PELA scaffolds for potential guided bone regeneration where an osteoconductive scaffold interior encouraging osteointegration and a nonadhesive surface discouraging fibrous tissue encapsulation is desired. This work demonstrated that by combining facile and readily translatable rapid prototyping approaches with unique biomaterial designs, biodegradable composite scaffolds with well-controlled macroporosities, spatially defined biological microenvironment, and useful handling characteristics can be developed. PMID:25025950

Electrospun silk fibroin scaffolds coated with reduced graphene promote neurite outgrowth of PC-12 cells under electrical stimulation.

Science.gov (United States)

Aznar-Cervantes, Salvador; Pagán, Ana; Martínez, Jose G; Bernabeu-Esclapez, Antonia; Otero, Toribio F; Meseguer-Olmo, Luis; Paredes, Juan I; Cenis, Jose L

2017-10-01

Novel approaches to neural research require biocompatible materials capable to act as electrode structures or scaffolds for tissue engineering in order to stimulate or restore the functionality of damaged tissues. This work offers promising results that indicate the potential use of electrospun silk fibroin (SF) scaffolds coated with reduced graphene oxide (rGO) in this sense. The coated material becomes conductor and electroactive. A complete characterisation of SF/rGO scaffolds is provided in terms of electrochemistry, mechanical behaviour and chemical conformation of fibroin. The excellent biocompatibility of this novel material is proved with cultures of PC-12 cells. The coating with rGO improved the adhesion of cells in comparison with cells growing onto the surface of pure SF scaffolds. Also, the use of SF/rGO scaffolds combined with electrical stimulation promoted the differentiation into neural phenotypes reaching comparable or even superior levels to those obtained by means of the traditional treatment with neural growth factor (NGF). Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Facile fabrication of poly(L-lactic acid) microsphere-incorporated calcium alginate/hydroxyapatite porous scaffolds based on Pickering emulsion templates.

Science.gov (United States)

Hu, Yang; Ma, Shanshan; Yang, Zhuohong; Zhou, Wuyi; Du, Zhengshan; Huang, Jian; Yi, Huan; Wang, Chaoyang

2016-04-01

In this study, we develop a facile one-pot approach to the fabrication of poly(L-lactic acid) (PLLA) microsphere-incorporated calcium alginate (ALG-Ca)/hydroxyapatite (HAp) porous scaffolds based on HAp nanoparticle-stabilized oil-in-water Pickering emulsion templates, which contain alginate in the aqueous phase and PLLA in the oil phase. The emulsion aqueous phase is solidified by in situ gelation of alginate with Ca(2+) released from HAp by decreasing pH with slow hydrolysis of D-gluconic acid δ-lactone (GDL) to produce emulsion droplet-incorporated gels, followed by freeze-drying to form porous scaffolds containing microspheres. The pore structure of porous scaffolds can be adjusted by varying the HAp or GDL concentration. The compressive tests show that the increase of HAp or GDL concentration is beneficial to improve the compressive property of porous scaffolds, while the excessive HAp can lead to the decrease in compressive property. Moreover, the swelling behavior studies display that the swelling ratios of porous scaffolds reduce with increasing HAp or GDL concentration. Furthermore, hydrophobic drug ibuprofen (IBU) and hydrophilic drug bovine serum albumin (BSA) are loaded into the microspheres and scaffold matrix, respectively. In vitro drug release results indicate that BSA has a rapid release while IBU has a sustained release in the dual drug-loaded scaffolds. In vitro cell culture experiments verify that mouse bone mesenchymal stem cells can proliferate on the porous scaffolds well, indicating the good biocompatibility of porous scaffolds. All these results demonstrate that the PLLA microsphere-incorporated ALG-Ca/HAp porous scaffolds have a promising potential for tissue engineering and drug delivery applications. Copyright © 2016 Elsevier B.V. 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.

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.

Hybrid chitosan-ß-glycerol phosphate-gelatin nano-/micro fibrous scaffolds with suitable mechanical and biological properties for tissue engineering.

Science.gov (United States)

Lotfi, Marzieh; Bagherzadeh, Roohollah; Naderi-Meshkin, Hojjat; Mahdipour, Elahe; Mafinezhad, Asghar; Sadeghnia, Hamid Reza; Esmaily, Habibollah; Maleki, Masoud; Hasssanzadeh, Halimeh; Ghayaour-Mobarhan, Majid; Bidkhori, Hamid Reza; Bahrami, Ahmad Reza

2016-03-01

Scaffold-based tissue engineering is considered as a promising approach in the regenerative medicine. Graft instability of collagen, by causing poor mechanical properties and rapid degradation, and their hard handling remains major challenges to be addressed. In this research, a composite structured nano-/microfibrous scaffold, made from a mixture of chitosan-ß-glycerol phosphate-gelatin (chitosan-GP-gelatin) using a standard electrospinning set-up was developed. Gelatin-acid acetic and chitosan ß-glycerol phosphate-HCL solutions were prepared at ratios of 30/70, 50/50, 70/30 (w/w) and their mechanical and biological properties were engineered. Furthermore, the pore structure of the fabricated nanofibrous scaffolds was investigated and predicted using a theoretical model. Higher gelatin concentrations in the polymer blend resulted in significant increase in mean pore size and its distribution. Interaction between the scaffold and the contained cells was also monitored and compared in the test and control groups. Scaffolds with higher chitosan concentrations showed higher rate of cell attachment with better proliferation property, compared with gelatin-only scaffolds. The fabricated scaffolds, unlike many other natural polymers, also exhibit non-toxic and biodegradable properties in the grafted tissues. In conclusion, the data clearly showed that the fabricated biomaterial is a biologically compatible scaffold with potential to serve as a proper platform for retaining the cultured cells for further application in cell-based tissue engineering, especially in wound healing practices. These results suggested the potential of using mesoporous composite chitosan-GP-gelatin fibrous scaffolds for engineering three-dimensional tissues with different inherent cell characteristics. © 2015 Wiley Periodicals, Inc.

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.

Enhanced osteogenic activity of poly(ester urea) scaffolds using facile post-3D printing peptide functionalization strategies.

Science.gov (United States)

Li, Shan; Xu, Yanyi; Yu, Jiayi; Becker, Matthew L

2017-10-01

Additive manufacturing has the potential to revolutionize regenerative medicine, but the harsh thermal or photochemical conditions during the 3D printing process limit the inclusion of drugs, growth factors and other biologics within the resulting scaffolds. Functionalization strategies that enable specific placement of bioactive species on the surface of 3D printed structures following the printing process afford a promising approach to sidestep the harsh conditions and incorporate these valuable bioactive molecules with precise control over concentration. Herein, resorbable polymer scaffolds were prepared from propargyl functionalized L-phenylalanine-based poly(ester urea)s (PEUs). Osteogenic growth peptide (OGP) or bone morphogenic protein-2 (BMP-2) peptides were immobilized on PEU scaffolds through surface available propargyl groups via copper-catalyzed azide alkyne cycloaddition (CuAAC) post 3D printing. The presence of either OGP or BMP-2 significantly enhanced hMSCs osteogenic differentiation compared to unfunctionalized scaffolds. Copyright © 2017 Elsevier Ltd. All rights reserved.

PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering.

Science.gov (United States)

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.

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.

A strategy for the diversity-oriented synthesis of macrocyclic scaffolds using multidimensional coupling

DEFF Research Database (Denmark)

Beckmann, Henning S G; Nie, Feilin; Hagerman, Caroline E

2013-01-01

the coupling reaction. We applied this step-efficient approach in a DOS of a library that consisted of 73 macrocyclic compounds based around 59 discrete scaffolds. The macrocycles prepared cover a broad range of different molecular shapes, as illustrated by principal moment-of-inertia analysis...

Scaffold diversification enhances effectiveness of a superlibrary of hyperthermophilic proteins.

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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.

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.

Biomimetic Materials and Fabrication Approaches for Bone Tissue Engineering.

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Kim, Hwan D; Amirthalingam, Sivashanmugam; Kim, Seunghyun L; Lee, Seunghun S; Rangasamy, Jayakumar; Hwang, Nathaniel S

2017-12-01

Various strategies have been explored to overcome critically sized bone defects via bone tissue engineering approaches that incorporate biomimetic scaffolds. Biomimetic scaffolds may provide a novel platform for phenotypically stable tissue formation and stem cell differentiation. In recent years, osteoinductive and inorganic biomimetic scaffold materials have been optimized to offer an osteo-friendly microenvironment for the osteogenic commitment of stem cells. Furthermore, scaffold structures with a microarchitecture design similar to native bone tissue are necessary for successful bone tissue regeneration. For this reason, various methods for fabricating 3D porous structures have been developed. Innovative techniques, such as 3D printing methods, are currently being utilized for optimal host stem cell infiltration, vascularization, nutrient transfer, and stem cell differentiation. In this progress report, biomimetic materials and fabrication approaches that are currently being utilized for biomimetic scaffold design are reviewed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model

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Giavaresi Gianluca

2010-09-01

Full Text Available Abstract Background Current research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-rich plasma (PRP to enhance the repair process of a collagen-hydroxyapatite scaffold in osteochondral defects in a sheep model. Methods PRP was added to a new, multi-layer gradient, nanocomposite scaffold that was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Twenty-four osteochondral lesions were created in sheep femoral condyles. The animals were randomised to three treatment groups: scaffold, scaffold loaded with autologous PRP, and empty defect (control. The animals were sacrificed and evaluated six months after surgery. Results Gross evaluation and histology of the specimens showed good integration of the chondral surface in both treatment groups. Significantly better bone regeneration and cartilage surface reconstruction were observed in the group treated with the scaffold alone. Incomplete bone regeneration and irregular cartilage surface integration were observed in the group treated with the scaffold where PRP was added. In the control group, no bone and cartilage defect healing occurred; defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. Conclusions The hydroxyapatite-collagen scaffold enhanced osteochondral lesion repair, but the combination with platelet growth factors did not have an additive effect; on the contrary, PRP administration had a negative effect on the results obtained by disturbing the regenerative process. In the scaffold + PRP group, highly amorphous cartilaginous repair tissue and poorly spatially organised underlying bone tissue were found.

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.

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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.

Scaffolding students’ reflective dialogues in the chemistry lab: challenging the cookbook

DEFF Research Database (Denmark)

Nielsen, Birgitte Lund; Hougaard, Rikke Frøhlich

The paper reports on a cross-case analysis comparing students’ activities and dialogue during BA level laboratory exercises, applying a mixed methods research design with video-data, student questionnaires and interviews. Our analysis identified specific affordances in relation to macro and micro......-scaffolding of students’ activities and dialogues, in order to stimulate them to work at higher cognitive levels. A specific lab-exercise in the course Macroscopic Physical Chemistry was redesigned with the aim of stimulating students’ metacognition both before and during the experimental work. The redesign included......-student dialogue on course content. Furthermore, dialogues between students and teaching assistant revealed elements of micro-scaffolding exploratory talk and a dialogic approach with open questions and prompts. The students expressed that the preparatory assignments and the dialogue with the teaching assistant...

Strategies for the solid-phase diversification of poly-L-proline-type II peptide mimic scaffolds and peptide scaffolds through guanidinylation.

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Flemer, Stevenson; Wurthmann, Alexander; Mamai, Ahmed; Madalengoitia, José S

2008-10-03

A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.

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.

Electrospun Nanofiber Scaffolds with Gradations in Fiber Organization

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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

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

Science.gov (United States)

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.

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

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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

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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.

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.

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.

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

Suitability of a PLCL fibrous scaffold for soft tissue engineering applications: A combined biological and mechanical characterisation.

Science.gov (United States)

Laurent, Cédric P; Vaquette, Cédryck; Liu, Xing; Schmitt, Jean-François; Rahouadj, Rachid

2018-04-01

Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.

Strategy for optimal side-branch positioning of bioresorbable vascular scaffolds in dedicated 2-stent techniques: Insights from optical coherence tomography

International Nuclear Information System (INIS)

Miyazaki, Tadashi; Costopoulos, Charis; Sato, Katsumasa; Naganuma, Toru; Panoulas, Vasileios F.; Figini, Filippo; Latib, Azeem; Colombo, Antonio

2014-01-01

We present a case of a left anterior descending artery/diagonal branch bifurcation successfully treated with a dedicated 2-stent technique utilizing bioresorbable vascular scaffolds, where the bifurcation angle did not strictly allow a T-stenting approach. We also propose a strategy to avoid or reduce scaffold overlap in the main branch, especially important in view of the bulkier size of these novel devices

Biological effects of functionalizing copolymer scaffolds with nanodiamond particles.

Science.gov (United States)

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

Scaffold-free Prevascularized Microtissue Spheroids for Pulp Regeneration.

Science.gov (United States)

Dissanayaka, W L; Zhu, L; Hargreaves, K M; Jin, L; Zhang, C

2014-12-01

Creating an optimal microenvironment that mimics the extracellular matrix (ECM) of natural pulp and securing an adequate blood supply for the survival of cell transplants are major hurdles that need to be overcome in dental pulp regeneration. However, many currently available scaffolds fail to mimic essential functions of natural ECM. The present study investigated a novel approach involving the use of scaffold-free microtissue spheroids of dental pulp stem cells (DPSCs) prevascularized by human umbilical vein endothelial cells (HUVECs) in pulp regeneration. In vitro-fabricated microtissue spheroids were inserted into the canal space of tooth-root slices and were implanted subcutaneously into immunodeficient mice. Histological examination revealed that, after four-week implantation, tooth-root slices containing microtissue spheroids resulted in well-vascularized and cellular pulp-like tissues, compared with empty tooth-root slices, which were filled with only subcutaneous fat tissue. Immunohistochemical staining indicated that the tissue found in the tooth-root slices was of human origin, as characterized by the expression of human mitochondria, and contained odontoblast-like cells organized along the dentin, as assessed by immunostaining for nestin and dentin sialoprotein (DSP). Vascular structures formed by HUVECs in vitro were successfully anastomosed with the host vasculature upon transplantation in vivo, as shown by immunostaining for human CD31. Collectively, these findings demonstrate that prevascularized, scaffold-free, microtissue spheroids can successfully regenerate vascular dental pulp-like tissue and also highlight the significance of the microtissue microenvironment as an optimal environment for successful pulp-regeneration strategies. © International & American Associations for Dental Research.

Improving osteointegration and osteogenesis of three-dimensional porous Ti6Al4V scaffolds by polydopamine-assisted biomimetic hydroxyapatite coating.

Science.gov (United States)

Li, Yong; Yang, Wei; Li, Xiaokang; Zhang, Xing; Wang, Cairu; Meng, Xiangfei; Pei, Yifeng; Fan, Xiangli; Lan, Pingheng; Wang, Chunhui; Li, Xiaojie; Guo, Zheng

2015-03-18

Titanium alloys with various porous structures can be fabricated by advanced additive manufacturing techniques, which are attractive for use as scaffolds for bone defect repair. However, modification of the scaffold surfaces, particularly inner surfaces, is critical to improve the osteointegration of these scaffolds. In this study, a biomimetic approach was employed to construct polydopamine-assisted hydroxyapatite coating (HA/pDA) onto porous Ti6Al4V scaffolds fabricated by the electron beam melting method. The surface modification was characterized with the field emission scanning electron microscopy, energy dispersive spectroscopy, water contact angle measurement, and confocal laser scanning microscopy. Attachment and proliferation of MC3T3-E1 cells on the scaffold surface were significantly enhanced by the HA/pDA coating compared to the unmodified surfaces. Additionally, MC3T3-E1 cells grown on the HA/pDA-coated Ti6Al4V scaffolds displayed significantly higher expression of runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 compared with bare Ti6Al4V scaffolds after culture for 14 days. Moreover, microcomputed tomography analysis and Van-Gieson staining of histological sections showed that HA/pDA coating on surfaces of porous Ti6Al4V scaffolds enhanced osteointegration and significantly promoted bone regeneration after implantation in rabbit femoral condylar defects for 4 and 12 weeks. Therefore, this study provides an alternative to biofunctionalized porous Ti6Al4V scaffolds with improved osteointegration and osteogenesis functions for orthopedic applications.

Bionic Design, Materials and Performance of Bone Tissue Scaffolds

Directory of Open Access Journals (Sweden)

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...

Engineering protein scaffolds for protein separation, biocatalysis and nanotechnology applications

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Liu, Fang

-coordinating function impaired was used in replace of the original full length dockerin domain. The truncated dockerin domain maintained its functionality as an effective affinity tag, and efficient EDTA mediated dissociation of the bound dockerin-intein tag was also realized. The regenerated ELP capturing scaffold was reused for additional purification cycles without any decrease in efficiency. The second objective was to assemble biocatalysts for biofuel cells. Three beta-NAD dependent dehydrogenases, alcohol dehydrogenase (ADH), formaldehyde dehydrogenase (FALDH) and formate dehydrogenase (FDH), were site-specifically co-localized onto the scaffolds displayed on the yeast surface based on the high-affinity interactions between three orthogonal cohesin/dockerin pairs. The assembled multi-enzyme cascades, which can completely convert methanol to CO2, showed improved production yield compared with that of the non-complexed enzyme mixture, indicating efficient substrate channeling among the three enzymes. This strategy can be easily extended to other complex cascade reactions for enzymatic fuel cell applications. To further explore the role of biotechnology toward environmental sustainability, Escherichia coli was engineered to express phytochelatin synthase, which converted glutathione into the metal-binding peptide phytochelatin (PC). PCs served as peptide scaffolds and mediated synthesis of CdS nanocrystals. This approach may be generalized to guide the in vitro self-assembly of a wide range of nanocrystals with different compositions and sizes.

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

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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.

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