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...

Teaching Design in Middle-School: Instructors' Concerns and Scaffolding Strategies

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Bamberger, Yael M.; Cahill, Clara S.

2013-04-01

This study deals with engineering education in the middle-school level. Its focus is instructors' concerns in teaching design, as well as scaffolding strategies that can help teachers deal with these concerns. Through participatory action research, nine instructors engaged in a process of development and instruction of a curriculum about energy along with engineering design. A 50-h curriculum was piloted during a summer camp for 38 middle-school students. Data was collected through instructors' materials: observation field notes, daily reflections and post-camp discussions. In addition, students' artifacts and planning graphical models were collected in order to explore how instructors' concerns were aligned with students' learning. Findings indicate three main tensions that reflect instructors' main concerns: how to provide sufficient scaffolding yet encourage creativity, how to scaffold hands-on experiences that promote mindful planning, and how to scaffold students' modeling practices. Pedagogical strategies for teaching design that developed through this work are described, as well as the ways they address the National Research Council (A framework for K-12 science education: practices, crosscutting concepts, and core ideas. National Academies Press, Washington, DC, 2011) core ideas of engineering education and the International Technological Literacy standards (ITEA in Standards for technological literacy, 3rd edn. International Technology education Association, Reston, VA, 2007).

Design and 3D Printing of Scaffolds and Tissues

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Jia An

2015-06-01

Full Text Available A growing number of three-dimensional (3D-printing processes have been applied to tissue engineering. This paper presents a state-of-the-art study of 3D-printing technologies for tissue-engineering applications, with particular focus on the development of a computer-aided scaffold design system; the direct 3D printing of functionally graded scaffolds; the modeling of selective laser sintering (SLS and fused deposition modeling (FDM processes; the indirect additive manufacturing of scaffolds, with both micro and macro features; the development of a bioreactor; and 3D/4D bioprinting. Technological limitations will be discussed so as to highlight the possibility of future improvements for new 3D-printing methodologies for tissue engineering.

Scaffolding Preservice Teachers' WebQuest Design: A Qualitative Study

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Wang, Feng; Hannafin, Michael J.

2009-01-01

This study examined how participating preservice teachers reported their perceptions and use of different scaffolds provided to support their WebQuest design. Sixteen preservice teachers participated in a succession of course activities designed to guide WebQuest design and development. Results indicated that while participants followed, adapted,…

New paradigms in internal architecture design and freeform fabrication of tissue engineering porous scaffolds.

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Yoo, Dongjin

2012-07-01

Advanced additive manufacture (AM) techniques are now being developed to fabricate scaffolds with controlled internal pore architectures in the field of tissue engineering. In general, these techniques use a hybrid method which combines computer-aided design (CAD) with computer-aided manufacturing (CAM) tools to design and fabricate complicated three-dimensional (3D) scaffold models. The mathematical descriptions of micro-architectures along with the macro-structures of the 3D scaffold models are limited by current CAD technologies as well as by the difficulty of transferring the designed digital models to standard formats for fabrication. To overcome these difficulties, we have developed an efficient internal pore architecture design system based on triply periodic minimal surface (TPMS) unit cell libraries and associated computational methods to assemble TPMS unit cells into an entire scaffold model. In addition, we have developed a process planning technique based on TPMS internal architecture pattern of unit cells to generate tool paths for freeform fabrication of tissue engineering porous scaffolds. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

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

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

2015-01-01

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

Design of a Novel Two-Component Hybrid Dermal Scaffold for the Treatment of Pressure Sores.

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Sharma, Vaibhav; Kohli, Nupur; Moulding, Dale; Afolabi, Halimat; Hook, Lilian; Mason, Chris; García-Gareta, Elena

2017-11-01

The aim of this study is to design a novel two-component hybrid scaffold using the fibrin/alginate porous hydrogel Smart Matrix combined to a backing layer of plasma polymerized polydimethylsiloxane (Sil) membrane to make the fibrin-based dermal scaffold more robust for the treatment of the clinically challenging pressure sores. A design criteria are established, according to which the Sil membranes are punched to avoid collection of fluid underneath. Manual peel test shows that native silicone does not attach to the fibrin/alginate component while the plasma polymerized silicone membranes are firmly bound to fibrin/alginate. Structural characterization shows that the fibrin/alginate matrix is intact after the addition of the Sil membrane. By adding a Sil membrane to the original fibrin/alginate scaffold, the resulting two-component scaffolds have a significantly higher shear or storage modulus G'. In vitro cell studies show that dermal fibroblasts remain viable, proliferate, and infiltrate the two-component hybrid scaffolds during the culture period. These results show that the design of a novel two-component hybrid dermal scaffold is successful according to the proposed design criteria. To the best of the authors' knowledge, this is the first study that reports the combination of a fibrin-based scaffold with a plasma-polymerized silicone membrane. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Impact of Collaborative Scaffolding in Educational Video Games on the Collaborative Support Skills of Middle School Students

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Loparev, Anna

2016-01-01

Collaboration is crucial to everything from product development in the workplace to research design in academia, yet there is no consensus on best practice when it comes to teaching collaborative skills. We explore one promising option: collaborative scaffolding in educational video games. Through this methodology, we can impart collaborative…

A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity.

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Lin, Cheng Yu; Kikuchi, Noboru; Hollister, Scott J

2004-05-01

An often-proposed tissue engineering design hypothesis is that the scaffold should provide a biomimetic mechanical environment for initial function and appropriate remodeling of regenerating tissue while concurrently providing sufficient porosity for cell migration and cell/gene delivery. To provide a systematic study of this hypothesis, the ability to precisely design and manufacture biomaterial scaffolds is needed. Traditional methods for scaffold design and fabrication cannot provide the control over scaffold architecture design to achieve specified properties within fixed limits on porosity. The purpose of this paper was to develop a general design optimization scheme for 3D internal scaffold architecture to match desired elastic properties and porosity simultaneously, by introducing the homogenization-based topology optimization algorithm (also known as general layout optimization). With an initial target for bone tissue engineering, we demonstrate that the method can produce highly porous structures that match human trabecular bone anisotropic stiffness using accepted biomaterials. In addition, we show that anisotropic bone stiffness may be matched with scaffolds of widely different porosity. Finally, we also demonstrate that prototypes of the designed structures can be fabricated using solid free-form fabrication (SFF) techniques.

Design and fabrication of biomimetic multiphased scaffolds for ligament-to-bone fixation.

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He, Jiankang; Zhang, Wenyou; Liu, Yaxiong; Li, Xiang; Li, Dichen; Jin, Zhongmin

2015-05-01

Conventional ligament grafts with single material composition cannot effectively integrate with the host bones due to mismatched properties and eventually affect their long-term function in vivo. Here we presented a multi-material strategy to design and fabricate composite scaffolds including ligament, interface and bone multiphased regions. The interface region consists of triphasic layers with varying material composition and porous structure to mimic native ligament-to-bone interface while the bone region contains polycaprolactone (PCL) anchor and microchanneled ceramic scaffolds to potentially provide combined mechanical and biological implant-bone fixation. Finite element analysis (FEA) demonstrated that the multiphased scaffolds with interference value smaller than 0.5 mm could avoid the fracture of ceramic scaffold during the implantation process, which was validated by in-vitro implanting the multiphased scaffolds into porcine joint bones. Pull-out experiment showed that the initial fixation between the multiphased scaffolds with 0.47 mm interference and the host bones could withstand the maximum force of 360.31±97.51 N, which can be improved by reinforcing the ceramic scaffolds with biopolymers. It is envisioned that the multiphased scaffold could potentially induce the regeneration of a new bone as well as interfacial tissue with the gradual degradation of the scaffold and subsequently realize long-term biological fixation of the implant with the host bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer.

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Gregor, Aleš; Filová, Eva; Novák, Martin; Kronek, Jakub; Chlup, Hynek; Buzgo, Matěj; Blahnová, Veronika; Lukášová, Věra; Bartoš, Martin; Nečas, Alois; Hošek, Jan

2017-01-01

The primary objective of Tissue engineering is a regeneration or replacement of tissues or organs damaged by disease, injury, or congenital anomalies. At present, Tissue engineering repairs damaged tissues and organs with artificial supporting structures called scaffolds. These are used for attachment and subsequent growth of appropriate cells. During the cell growth gradual biodegradation of the scaffold occurs and the final product is a new tissue with the desired shape and properties. In recent years, research workplaces are focused on developing scaffold by bio-fabrication techniques to achieve fast, precise and cheap automatic manufacturing of these structures. Most promising techniques seem to be Rapid prototyping due to its high level of precision and controlling. However, this technique is still to solve various issues before it is easily used for scaffold fabrication. In this article we tested printing of clinically applicable scaffolds with use of commercially available devices and materials. Research presented in this article is in general focused on "scaffolding" on a field of bone tissue replacement. Commercially available 3D printer and Polylactic acid were used to create originally designed and possibly suitable scaffold structures for bone tissue engineering. We tested printing of scaffolds with different geometrical structures. Based on the osteosarcoma cells proliferation experiment and mechanical testing of designed scaffold samples, it will be stated that it is likely not necessary to keep the recommended porosity of the scaffold for bone tissue replacement at about 90%, and it will also be clarified why this fact eliminates mechanical properties issue. Moreover, it is demonstrated that the size of an individual pore could be double the size of the recommended range between 0.2-0.35 mm without affecting the cell proliferation. Rapid prototyping technique based on Fused deposition modelling was used for the fabrication of designed scaffold

Design control for clinical translation of 3D printed modular scaffolds.

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Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach

Design and Validation of a Cyclic Strain Bioreactor to Condition Spatially-Selective Scaffolds in Dual Strain Regimes

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J. Matthew Goodhart

2014-03-01

Full Text Available The objective of this study was to design and validate a unique bioreactor design for applying spatially selective, linear, cyclic strain to degradable and non-degradable polymeric fabric scaffolds. This system uses a novel three-clamp design to apply cyclic strain via a computer controlled linear actuator to a specified zone of a scaffold while isolating the remainder of the scaffold from strain. Image analysis of polyethylene terephthalate (PET woven scaffolds subjected to a 3% mechanical stretch demonstrated that the stretched portion of the scaffold experienced 2.97% ± 0.13% strain (mean ± standard deviation while the unstretched portion experienced 0.02% ± 0.18% strain. NIH-3T3 fibroblast cells were cultured on the PET scaffolds and half of each scaffold was stretched 5% at 0.5 Hz for one hour per day for 14 days in the bioreactor. Cells were checked for viability and proliferation at the end of the 14 day period and levels of glycosaminoglycan (GAG and collagen (hydroxyproline were measured as indicators of extracellular matrix production. Scaffolds in the bioreactor showed a seven-fold increase in cell number over scaffolds cultured statically in tissue culture plastic petri dishes (control. Bioreactor scaffolds showed a lower concentration of GAG deposition per cell as compared to the control scaffolds largely due to the great increase in cell number. A 75% increase in hydroxyproline concentration per cell was seen in the bioreactor stretched scaffolds as compared to the control scaffolds. Surprisingly, little differences were experienced between the stretched and unstretched portions of the scaffolds for this study. This was largely attributed to the conditioned and shared media effect. Results indicate that the bioreactor system is capable of applying spatially-selective, linear, cyclic strain to cells growing on polymeric fabric scaffolds and evaluating the cellular and matrix responses to the applied strains.

An accomplished teacher's use of scaffolding during a second-grade unit on designing games.

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Chen, Weiyun; Rovegno, Inez; Cone, Stephen L; Cone, Theresa P

2012-06-01

The purpose of this study was to describe how an accomplished teacher taught second-grade students to design games that integrated movement and mathematics content. The participants were one physical education teacher; a classroom teacher, and an intact class of 20 second-grade students. Qualitative data were gathered through videotaping of all lessons, descriptions of 20 children's responses to all lesson segments, and interviews with all participants. In keeping with constructivist principles, the teacher used a progression of tasks and multiple instructional techniques to scaffold the design process allowing children to design games that were meaningful to them. Contrary to descriptions of scaffolding fading across a unit, in this study the scaffolding was a function of the interaction between learners' needs and task content.

An Insilico Design of Nanoclay Based Nanocomposites and Scaffolds in Bone Tissue Engineering

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Sharma, Anurag

A multiscale in silico approach to design polymer nanocomposites and scaffolds for bone tissue engineering applications is described in this study. This study focuses on the role of biomaterials design and selection, structural integrity and mechanical properties evolution during degradation and tissue regeneration in the successful design of polymer nanocomposite scaffolds. Polymer nanocomposite scaffolds are synthesized using aminoacid modified montmorillonite nanoclay with biomineralized hydroxyapatite and polycaprolactone (PCL/in situ HAPclay). Representative molecular models of polymer nanocomposite system are systematically developed using molecular dynamics (MD) technique and successfully validated using material characterization techniques. The constant force steered molecular dynamics (fSMD) simulation results indicate a two-phase nanomechanical behavior of the polymer nanocomposite. The MD and fSMD simulations results provide quantitative contributions of molecular interactions between different constituents of representative models and their effect on nanomechanical responses of nanoclay based polymer nanocomposite system. A finite element (FE) model of PCL/in situ HAPclay scaffold is built using micro-computed tomography images and bridging the nanomechanical properties obtained from fSMD simulations into the FE model. A new reduction factor, K is introduced into modeling results to consider the effect of wall porosity of the polymer scaffold. The effect of accelerated degradation under alkaline conditions and human osteoblast cells culture on the evolution of mechanical properties of scaffolds are studied and the damage mechanics based analytical models are developed. Finally, the novel multiscale models are developed that incorporate the complex molecular and microstructural properties, mechanical properties at nanoscale and structural levels and mechanical properties evolution during degradation and tissue formation in the polymer nanocomposite

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

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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.

An Overview of Scaffold Design and Fabrication Technology for Engineered Knee Meniscus

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Jie Sun

2017-01-01

Full Text Available Current surgical treatments for meniscal tears suffer from subsequent degeneration of knee joints, limited donor organs and inconsistent post-treatment results. Three clinical scaffolds (Menaflex CMI, Actifit® scaffold and NUsurface® Meniscus Implant are available on the market, but additional data are needed to properly evaluate their safety and effectiveness. Thus, many scaffold-based research activities have been done to develop new materials, structures and fabrication technologies to mimic native meniscus for cell attachment and subsequent tissue development, and restore functionalities of injured meniscus for long-term effects. This study begins with a synopsis of relevant structural features of meniscus and goes on to describe the critical considerations. Promising advances made in the field of meniscal scaffolding technology, in terms of biocompatible materials, fabrication methods, structure design and their impact on mechanical and biological properties are discussed in detail. Among all the scaffolding technologies, additive manufacturing (AM is very promising because of its ability to precisely control fiber diameter, orientation, and pore network micro-architecture to mimic the native meniscus microenvironment.

Controlling the extrudate swell in melt extrusion additive manufacturing of 3D scaffolds: a designed experiment.

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Yousefi, Azizeh-Mitra; Smucker, Byran; Naber, Alex; Wyrick, Cara; Shaw, Charles; Bennett, Katelyn; Szekely, Sarah; Focke, Carlie; Wood, Katherine A

2018-02-01

Tissue engineering using three-dimensional porous scaffolds has shown promise for the restoration of normal function in injured and diseased tissues and organs. Rigorous control over scaffold architecture in melt extrusion additive manufacturing is highly restricted mainly due to pronounced variations in the deposited strand diameter upon any variations in process conditions and polymer viscoelasticity. We have designed an I-optimal, split-plot experiment to study the extrudate swell in melt extrusion additive manufacturing and to control the scaffold architecture. The designed experiment was used to generate data to relate three responses (swell, density, and modulus) to a set of controllable factors (plotting needle diameter, temperature, pressure, and the dispensing speed). The fitted regression relationships were used to optimize the three responses simultaneously. The swell response was constrained to be close to 1 while maximizing the modulus and minimizing the density. Constraining the extrudate swell to 1 generates design-driven scaffolds, with strand diameters equal to the plotting needle diameter, and allows a greater control over scaffold pore size. Hence, the modulus of the scaffolds can be fully controlled by adjusting the in-plane distance between the deposited strands. To the extent of the model's validity, we can eliminate the effect of extrudate swell in designing these scaffolds, while targeting a range of porosity and modulus appropriate for bone tissue engineering. The result of this optimization was a predicted modulus of 14 MPa and a predicted density of 0.29 g/cm 3 (porosity ≈ 75%) using polycaprolactone as scaffold material. These predicted responses corresponded to factor levels of 0.6 μm for the plotting needle diameter, plotting pressure of 2.5 bar, melt temperature of 113.5 °C, and dispensing speed of 2 mm/s. The validation scaffold enabled us to quantify the percentage difference for the predictions, which was 9.5% for the

Core-shell designed scaffolds for drug delivery and tissue engineering.

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Perez, Roman A; Kim, Hae-Won

2015-07-01

Scaffolds that secure and deliver therapeutic ingredients like signaling molecules and stem cells hold great promise for drug delivery and tissue engineering. Employing a core-shell design for scaffolds provides a promising solution. Some unique methods, such as co-concentric nozzle extrusion, microfluidics generation, and chemical confinement reactions, have been successful in producing core-shelled nano/microfibers and nano/microspheres. Signaling molecules and drugs, spatially allocated to the core and/or shell part, can be delivered in a controllable and sequential manner for optimal therapeutic effects. Stem cells can be loaded within the core part on-demand, safely protected from the environments, which ultimately affords ex vivo culture and in vivo tissue engineering. The encapsulated cells experience three-dimensional tissue-mimic microenvironments in which therapeutic molecules are secreted to the surrounding tissues through the semi-permeable shell. Tuning the material properties of the core and shell, changing the geometrical parameters, and shaping them into proper forms significantly influence the release behaviors of biomolecules and the fate of the cells. This topical issue highlights the immense usefulness of core-shell designs for the therapeutic actions of scaffolds in the delivery of signaling molecules and stem cells for tissue regeneration and disease treatment. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

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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.

A combinatorial approach towards the design of nanofibrous scaffolds for chondrogenesis

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Ahmed, Maqsood; Ramos, Tiago André Da Silva; Damanik, Febriyani; Quang Le, Bach; Wieringa, Paul; Bennink, Martin; van Blitterswijk, Clemens; de Boer, Jan; Moroni, Lorenzo

2015-10-01

The extracellular matrix (ECM) is a three-dimensional (3D) structure composed of proteinaceous fibres that provide physical and biological cues to direct cell behaviour. Here, we build a library of hybrid collagen-polymer fibrous scaffolds with nanoscale dimensions and screen them for their ability to grow chondrocytes for cartilage repair. Poly(lactic acid) and poly (lactic-co-glycolic acid) at two different monomer ratios (85:15 and 50:50) were incrementally blended with collagen. Physical properties (wettability and stiffness) of the scaffolds were characterized and related to biological performance (proliferation, ECM production, and gene expression) and structure-function relationships were developed. We found that soft scaffolds with an intermediate wettability composed of the highly biodegradable PLGA50:50 and collagen, in two ratios (40:60 and 60:40), were optimal for chondrogenic differentiation of ATDC5 cells as determined by increased ECM production and enhanced cartilage specific gene expression. Long-term cultures indicated a stable phenotype with minimal de-differentiation or hypertrophy. The combinatorial methodology applied herein is a promising approach for the design and development of scaffolds for regenerative medicine.

Finite-element design and optimization of a three-dimensional tetrahedral porous titanium scaffold for the reconstruction of mandibular defects.

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Luo, Danmei; Rong, Qiguo; Chen, Quan

2017-09-01

Reconstruction of segmental defects in the mandible remains a challenge for maxillofacial surgery. The use of porous scaffolds is a potential method for repairing these defects. Now, additive manufacturing techniques provide a solution for the fabrication of porous scaffolds with specific geometrical shapes and complex structures. The goal of this study was to design and optimize a three-dimensional tetrahedral titanium scaffold for the reconstruction of mandibular defects. With a fixed strut diameter of 0.45mm and a mean cell size of 2.2mm, a tetrahedral structural porous scaffold was designed for a simulated anatomical defect derived from computed tomography (CT) data of a human mandible. An optimization method based on the concept of uniform stress was performed on the initial scaffold to realize a minimal-weight design. Geometric and mechanical comparisons between the initial and optimized scaffold show that the optimized scaffold exhibits a larger porosity, 81.90%, as well as a more homogeneous stress distribution. These results demonstrate that tetrahedral structural titanium scaffolds are feasible structures for repairing mandibular defects, and that the proposed optimization scheme has the ability to produce superior scaffolds for mandibular reconstruction with better stability, higher porosity, and less weight. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration

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G-S Huang

2013-10-01

Full Text Available Three-dimensional (3D cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC spheroids were made by solid freeform fabrication (SFF from the solution of poly(D,L-lactide-co-glycolide. Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.

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

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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

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

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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

Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.

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McLellan, Jason S; Correia, Bruno E; Chen, Man; Yang, Yongping; Graham, Barney S; Schief, William R; Kwong, Peter D

2011-06-24

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required. Published by Elsevier Ltd.

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.

Frontiers in biomaterials the design, synthetic strategies and biocompatibility of polymer scaffolds for biomedical application

CERN Document Server

Cao, Shunsheng

2014-01-01

Frontiers in Biomaterials: The Design, Synthetic Strategies and Biocompatibility of Polymer Scaffolds for Biomedical Application, Volume 1" highlights the importance of biomaterials and their interaction with biological system. The need for the development of biomaterials as scaffold for tissue regeneration is driven by the increasing demands for materials that mimic functions of extracellular matrices of body tissues.This ebook covers the latest challenges on the biocompatibility of scaffold overtime after implantation and discusses the requirement of innovative technologies and strategies f

Bioresorbable scaffolds for bone tissue engineering: optimal design, fabrication, mechanical testing and scale-size effects analysis.

Science.gov (United States)

Coelho, Pedro G; Hollister, Scott J; Flanagan, Colleen L; Fernandes, Paulo R

2015-03-01

Bone scaffolds for tissue regeneration require an optimal trade-off between biological and mechanical criteria. Optimal designs may be obtained using topology optimization (homogenization approach) and prototypes produced using additive manufacturing techniques. However, the process from design to manufacture remains a research challenge and will be a requirement of FDA design controls to engineering scaffolds. This work investigates how the design to manufacture chain affects the reproducibility of complex optimized design characteristics in the manufactured product. The design and prototypes are analyzed taking into account the computational assumptions and the final mechanical properties determined through mechanical tests. The scaffold is an assembly of unit-cells, and thus scale size effects on the mechanical response considering finite periodicity are investigated and compared with the predictions from the homogenization method which assumes in the limit infinitely repeated unit cells. Results show that a limited number of unit-cells (3-5 repeated on a side) introduce some scale-effects but the discrepancies are below 10%. Higher discrepancies are found when comparing the experimental data to numerical simulations due to differences between the manufactured and designed scaffold feature shapes and sizes as well as micro-porosities introduced by the manufacturing process. However good regression correlations (R(2) > 0.85) were found between numerical and experimental values, with slopes close to 1 for 2 out of 3 designs. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Macro- and micro-designed chitosan-alginate scaffold architecture by three-dimensional printing and directional freezing

International Nuclear Information System (INIS)

Reed, Stephanie; Wu, Benjamin M; Lau, Grace; Delattre, Benjamin; Lopez, David Don; Tomsia, Antoni P

2016-01-01

While many tissue-engineered constructs aim to treat cartilage defects, most involve chondrocyte or stem cell seeding on scaffolds. The clinical application of cell-based techniques is limited due to the cost of maintaining cellular constructs on the shelf, potential immune response to allogeneic cell lines, and autologous chondrocyte sources requiring biopsy from already diseased or injured, scarce tissue. An acellular scaffold that can induce endogenous influx and homogeneous distribution of native stem cells from bone marrow holds great promise for cartilage regeneration. This study aims to develop such an acellular scaffold using designed, channeled architecture that simultaneously models the native zones of articular cartilage and subchondral bone. Highly porous, hydrophilic chitosan-alginate (Ch-Al) scaffolds were fabricated in three-dimensionally printed (3DP) molds designed to create millimeter scale macro-channels. Different polymer preform casting techniques were employed to produce scaffolds from both negative and positive 3DP molds. Macro-channeled scaffolds improved cell suspension distribution and uptake overly randomly porous scaffolds, with a wicking volumetric flow rate of 445.6 ± 30.3 mm 3 s −1 for aqueous solutions and 177 ± 16 mm 3 s −1 for blood. Additionally, directional freezing was applied to Ch-Al scaffolds, resulting in lamellar pores measuring 300 μm and 50 μm on the long and short axes, thus creating micrometer scale micro-channels. After directionally freezing Ch-Al solution cast in 3DP molds, the combined macro- and micro-channeled scaffold architecture enhanced cell suspension uptake beyond either macro- or micro-channels alone, reaching a volumetric flow rate of 1782.1 ± 48 mm 3 s −1 for aqueous solutions and 440.9 ± 0.5 mm 3 s −1 for blood. By combining 3DP and directional freezing, we can control the micro- and macro-architecture of Ch-Al to drastically improve cell influx into and distribution within the

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.

Computer-aided design of microvasculature systems for use in vascular scaffold production

International Nuclear Information System (INIS)

Mondy, William Lafayette; Cameron, Don; Timmermans, Jean-Pierre; De Clerck, Nora; Sasov, Alexander; Casteleyn, Christophe; Piegl, Les A

2009-01-01

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Computer-aided design of microvasculature systems for use in vascular scaffold production

Energy Technology Data Exchange (ETDEWEB)

Mondy, William Lafayette [Department of Chemical and Biomedical Engineering, University of South Florida, FL (United States); Cameron, Don [Department of Pathology and Cell Biology, College of Medicine, University of South Florida, FL (United States); Timmermans, Jean-Pierre [Department of Veterinary Sciences, University of Antwerp (Belgium); De Clerck, Nora [Department of Biomedical Sciences University of Antwerp (Belgium); Sasov, Alexander [Skyscan (Belgium); Casteleyn, Christophe [College of Veterinary Medicine, Ghent University (Belgium); Piegl, Les A [Department of Computer Science and Engineering, University of South Florida, FL (United States)

2009-09-15

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

Computer-aided design of microvasculature systems for use in vascular scaffold production.

Science.gov (United States)

Mondy, William Lafayette; Cameron, Don; Timmermans, Jean-Pierre; De Clerck, Nora; Sasov, Alexander; Casteleyn, Christophe; Piegl, Les A

2009-09-01

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues. In our first paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the possibility of using vascular tissues to produce data capable of aiding the design of vascular tree scaffolding, which would help in the reverse engineering of a complete vascular tree system including capillary bed structures. In this paper, we used STL models of large datasets of computer-aided design (CAD) data of vascular structures which contained capillary structures that mimic those in the dermal layers of rabbit skin. Using CAD software we created from 3D STL models a bio-CAD design for the development of capillary-containing vascular tree scaffolding for skin. This method is designed to enhance a variety of therapeutic protocols including, but not limited to, organ and tissue repair, systemic disease mediation and cell/tissue transplantation therapy. Our successful approach to in vitro vasculogenesis will allow the bioengineering of various other types of 3D tissue structures, and as such greatly expands the potential applications of biomedical engineering technology into the fields of biomedical research and medicine.

The Effectiveness of Scaffolding Design in Training Writing Skills Physics Teaching Materials

Directory of Open Access Journals (Sweden)

Parlindungan Sinaga

2015-01-01

Full Text Available Result of field studies showed low writing skill of teachers in teaching material. The root of the problem lies in their inability on translating description of teaching material into writing. This research focused on the effectiveness of scaffolding design. The scaffolding design was tested in the selected topics of physics courses for pre-service teachers through learning to write activity approach. The treatment effectiveness was determined by considering the effect size and normalized gain percentage, while the hypothesis was tested using “the Kruskal-Wallis test”. The research results showed that scaffolding between the stages of planning and translating plans into text was effective in improving pre-service physics teachers’ ability of writing physics teaching materials and was similarly effective in improving their conceptual understanding of the topics of electromagnetism, waves, and optics. Learning to write activity implemented in the course of physics with selected topics was effective in improving the ability of pre-service teachers in translating among different modes of representation and making multiple concept representations. The hypothesis test demonstrated that there was a significant difference in the abilities of writing teaching materials and conceptual understanding between experimental and control classes.

Cyclic deformation-induced solute transport in tissue scaffolds with computer designed, interconnected, pore networks: experiments and simulations.

Science.gov (United States)

Den Buijs, Jorn Op; Dragomir-Daescu, Dan; Ritman, Erik L

2009-08-01

Nutrient supply and waste removal in porous tissue engineering scaffolds decrease from the periphery to the center, leading to limited depth of ingrowth of new tissue into the scaffold. However, as many tissues experience cyclic physiological strains, this may provide a mechanism to enhance solute transport in vivo before vascularization of the scaffold. The hypothesis of this study was that pore cross-sectional geometry and interconnectivity are of major importance for the effectiveness of cyclic deformation-induced solute transport. Transparent elastic polyurethane scaffolds, with computer-programmed design of pore networks in the form of interconnected channels, were fabricated using a 3D printing and injection molding technique. The scaffold pores were loaded with a colored tracer for optical contrast, cyclically compressed with deformations of 10 and 15% of the original undeformed height at 1.0 Hz. Digital imaging was used to quantify the spatial distribution of the tracer concentration within the pores. Numerical simulations of a fluid-structure interaction model of deformation-induced solute transport were compared to the experimental data. The results of experiments and modeling agreed well and showed that pore interconnectivity heavily influences deformation-induced solute transport. Pore cross-sectional geometry appears to be of less relative importance in interconnected pore networks. Validated computer models of solute transport can be used to design optimal scaffold pore geometries that will enhance the convective transport of nutrients inside the scaffold and the removal of waste, thus improving the cell survivability deep inside the scaffold.

Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects

OpenAIRE

Roohani-Esfahani, Seyed-Iman; Newman, Peter; Zreiqat, Hala

2016-01-01

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100?150?MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110?MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1?10?MPa compressive...

Scaffolded Instruction Improves Student Understanding of the Scientific Method & Experimental Design

Science.gov (United States)

D'Costa, Allison R.; Schlueter, Mark A.

2013-01-01

Implementation of a guided-inquiry lab in introductory biology classes, along with scaffolded instruction, improved students' understanding of the scientific method, their ability to design an experiment, and their identification of experimental variables. Pre- and postassessments from experimental versus control sections over three semesters…

Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects

Science.gov (United States)

Roohani-Esfahani, Seyed-Iman; Newman, Peter; Zreiqat, Hala

2016-01-01

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100-150 MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110 MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1-10 MPa compressive cyclic load), failure reliability and flexural strength (30 MPa) compared with those for conventional architecture. The obtained strength is 150 times greater than values reported for polymeric and composite scaffolds and 5 times greater than reported values for ceramic and glass scaffolds at similar porosity. These scaffolds open avenues for treatment of load bearing bone defects in orthopaedic, dental and maxillofacial applications.

Novel scaffold design with multi-grooved PLA fibers

International Nuclear Information System (INIS)

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

2011-01-01

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

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…

Mechanical, Permeability, and Degradation Properties of 3D Designed Poly(1,8 Octanediol-co-Citrate)(POC) Scaffolds for Soft Tissue Engineering

Science.gov (United States)

Jeong, Claire G.; Hollister, Scott J.

2015-01-01

Poly(1,8-octanediol-co-citric acid) (POC) is a synthetic biodegradable elastomer that can be processed into 3D scaffolds for tissue engineering. We investigated the effect of designed porosity on the mechanical properties, permeability and degradation profiles of the POC scaffolds. For mechanical properties, scaffold compressive data was fit to a 1D nonlinear elastic model and solid tensile data was fit to a Neohookean incompressible nonlinear elastic model. Chondrocytes were seeded on scaffolds to assess the biocompatibility of POC. Increased porosity was associated with increased degradation rate, increased permeability, and decreased mechanical stiffness which also became less nonlinear. Scaffold characterization in this paper will provide design guidance for POC scaffolds to meet the mechanical and biological parameters needed for engineering soft tissues such as cartilage. PMID:20091910

Sterilization of collagen scaffolds designed for peripheral nerve regeneration: Effect on microstructure, degradation and cellular colonization

International Nuclear Information System (INIS)

Monaco, Graziana; Cholas, Rahmatullah; Salvatore, Luca; Madaghiele, Marta; Sannino, Alessandro

2017-01-01

In this study we investigated the impact of three different sterilization methods, dry heat (DHS), ethylene oxide (EtO) and electron beam radiation (β), on the properties of cylindrical collagen scaffolds with longitudinally oriented pore channels, specifically designed for peripheral nerve regeneration. Scanning electron microscopy, mechanical testing, quantification of primary amines, differential scanning calorimetry and enzymatic degradation were performed to analyze possible structural and chemical changes induced by the sterilization. Moreover, in vitro proliferation and infiltration of the rat Schwann cell line RSC96 within the scaffolds was evaluated, up to 10 days of culture. No major differences in morphology and compressive stiffness were observed among scaffolds sterilized by the different methods, as all samples showed approximately the same structure and stiffness as the unsterilized control. Proliferation, infiltration, distribution and morphology of RSC96 cells within the scaffolds were also comparable throughout the duration of the cell culture study, regardless of the sterilization treatment. However, we found a slight increase of chemical crosslinking upon sterilization (EtO < DHS < β), together with an enhanced resistance to denaturation of the EtO treated scaffolds and a significantly accelerated enzymatic degradation of the β sterilized scaffolds. The results demonstrated that β irradiation impaired the scaffold properties to a greater extent, whereas EtO exposure appeared as the most suitable method for the sterilization of the proposed scaffolds. - Highlights: • Production of longitudinally oriented collagen scaffolds for nerve regeneration • Control of pore structure and crosslinking • Impact of terminal sterilization on the scaffold properties • Proliferation and infiltration of Schwann cells within the sterilized scaffolds

Sterilization of collagen scaffolds designed for peripheral nerve regeneration: Effect on microstructure, degradation and cellular colonization

Energy Technology Data Exchange (ETDEWEB)

Monaco, Graziana [Department of Engineering for Innovation, University of Salento, Via per Monteroni, 73100 Lecce (Italy); Dhitech Scarl – Distretto Tecnologico High Tech, Via per Monteroni, 73100 Lecce (Italy); Cholas, Rahmatullah; Salvatore, Luca [Department of Engineering for Innovation, University of Salento, Via per Monteroni, 73100 Lecce (Italy); Madaghiele, Marta, E-mail: marta.madaghiele@unisalento.it [Department of Engineering for Innovation, University of Salento, Via per Monteroni, 73100 Lecce (Italy); Sannino, Alessandro [Department of Engineering for Innovation, University of Salento, Via per Monteroni, 73100 Lecce (Italy)

2017-02-01

In this study we investigated the impact of three different sterilization methods, dry heat (DHS), ethylene oxide (EtO) and electron beam radiation (β), on the properties of cylindrical collagen scaffolds with longitudinally oriented pore channels, specifically designed for peripheral nerve regeneration. Scanning electron microscopy, mechanical testing, quantification of primary amines, differential scanning calorimetry and enzymatic degradation were performed to analyze possible structural and chemical changes induced by the sterilization. Moreover, in vitro proliferation and infiltration of the rat Schwann cell line RSC96 within the scaffolds was evaluated, up to 10 days of culture. No major differences in morphology and compressive stiffness were observed among scaffolds sterilized by the different methods, as all samples showed approximately the same structure and stiffness as the unsterilized control. Proliferation, infiltration, distribution and morphology of RSC96 cells within the scaffolds were also comparable throughout the duration of the cell culture study, regardless of the sterilization treatment. However, we found a slight increase of chemical crosslinking upon sterilization (EtO < DHS < β), together with an enhanced resistance to denaturation of the EtO treated scaffolds and a significantly accelerated enzymatic degradation of the β sterilized scaffolds. The results demonstrated that β irradiation impaired the scaffold properties to a greater extent, whereas EtO exposure appeared as the most suitable method for the sterilization of the proposed scaffolds. - Highlights: • Production of longitudinally oriented collagen scaffolds for nerve regeneration • Control of pore structure and crosslinking • Impact of terminal sterilization on the scaffold properties • Proliferation and infiltration of Schwann cells within the sterilized scaffolds.

Characterizing nanoscale topography of the aortic heart valve basement membrane for tissue engineering heart valve scaffold design.

Science.gov (United States)

Brody, Sarah; Anilkumar, Thapasimuthu; Liliensiek, Sara; Last, Julie A; Murphy, Christopher J; Pandit, Abhay

2006-02-01

A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane.

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.

Fabrication and characterization of electrospun poly-L-lactide/gelatin graded tubular scaffolds: Toward a new design for performance enhancement in vascular tissue engineering

Directory of Open Access Journals (Sweden)

A. Yazdanpanah

2015-10-01

Full Text Available In this study, a new design of graded tubular scaffolds have been developed for the performance enhancement in vascular tissue engineering. The graded poly-L-lactide (PLLA and gelatin fibrous scaffolds produced by electrospining were then characterized. The morphology, degradability, porosity, pore size and mechanical properties of four tubular scaffolds (graded PLLA/gelatin, layered PLLA/gelatin, PLLA and gelatin scaffolds have been investigated. The tensile tests demonstrated that the mechanical strength and also the estimated burst pressure of the graded scaffolds were significantly increased in comparison with the layered and gelatin scaffolds. This new design, resulting in an increase in the mechanical properties, suggested the widespread use of these scaffolds in vascular tissue engineering in order to prepare more strengthened vessels.

Digital design of scaffold for mandibular defect repair based on tissue engineering.

Science.gov (United States)

Liu, Yun-feng; Zhu, Fu-dong; Dong, Xing-tao; Peng, Wei

2011-09-01

Mandibular defect occurs more frequently in recent years, and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws. Tissue engineering, which is a hot research field of biomedical engineering, provides a new direction for mandibular defect repair. As the basis and key part of tissue engineering, scaffolds have been widely and deeply studied in regards to the basic theory, as well as the principle of biomaterial, structure, design, and fabrication method. However, little research is targeted at tissue regeneration for clinic repair operations. Since mandibular bone has a special structure, rather than uniform and regular structure in existing studies, a methodology based on tissue engineering is proposed for mandibular defect repair in this paper. Key steps regarding scaffold digital design, such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail. By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping, the feasibility and effectiveness of the proposed methodology are properly verified. More works about mechanical and biological improvements need to be done to promote its clinical application in future.

Digital design of scaffold for mandibular defect repair based on tissue engineering

Institute of Scientific and Technical Information of China (English)

Yun-feng LIU; Fu-dong ZHU; Xing-tao DONG; Wei PENG

2011-01-01

Mandibular defect occurs more frequently in recent years,and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws.Tissue engineering,which is a hot research field of biomedical engineering,provides a new direction for mandibular defect repair.As the basis and key part of tissue engineering,scaffolds have been widely and deeply studied in regards to the basic theory,as well as the principle of biomaterial,structure,design,and fabrication method.However,little research is targeted at tissue regeneration for clinic repair operations.Since mandibular bone has a special structure,rather than uniform and regular structure in existing studies,a methodology based on tissue engineering is proposed for mandibular defect repair in this paper.Key steps regarding scaffold digital design,such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail.By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping,the feasibility and effectiveness of the proposed methodology are properly verified.More works about mechanical and biological improvements need to be done to promote its clinical application in future.

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.…

Application of quality by design for 3D printed bone prostheses and scaffolds.

Science.gov (United States)

Martinez-Marquez, Daniel; Mirnajafizadeh, Ali; Carty, Christopher P; Stewart, Rodney A

2018-01-01

3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. While a number of comprehensive quality frameworks have been developed in recent decades to ensure that the manufacturing of medical devices produces reliable products, they are centred on the traditional context of standardised manufacturing techniques. The advent of 3D printing technologies and the prospects for mass customisation provides significant market opportunities, but also presents a serious challenge to regulatory bodies tasked with managing and assuring product quality and safety. Before 3D printing bone prostheses and scaffolds can gain traction, industry stakeholders, such as regulators, clients, medical practitioners, insurers, lawyers, and manufacturers, would all require a high degree of confidence that customised manufacturing can achieve the same quality outcomes as standardised manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses can help to ensure that products are designed and manufactured correctly from the beginning without errors. This paper reports on the adaptation of the QbD approach for the development process of 3D printed custom bone prosthesis and scaffolds. This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review

Application of quality by design for 3D printed bone prostheses and scaffolds

Science.gov (United States)

Martinez-Marquez, Daniel; Mirnajafizadeh, Ali; Carty, Christopher P.

2018-01-01

3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. While a number of comprehensive quality frameworks have been developed in recent decades to ensure that the manufacturing of medical devices produces reliable products, they are centred on the traditional context of standardised manufacturing techniques. The advent of 3D printing technologies and the prospects for mass customisation provides significant market opportunities, but also presents a serious challenge to regulatory bodies tasked with managing and assuring product quality and safety. Before 3D printing bone prostheses and scaffolds can gain traction, industry stakeholders, such as regulators, clients, medical practitioners, insurers, lawyers, and manufacturers, would all require a high degree of confidence that customised manufacturing can achieve the same quality outcomes as standardised manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses can help to ensure that products are designed and manufactured correctly from the beginning without errors. This paper reports on the adaptation of the QbD approach for the development process of 3D printed custom bone prosthesis and scaffolds. This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review

Is There a Consensus on Consensus Methodology? Descriptions and Recommendations for Future Consensus Research.

Science.gov (United States)

Waggoner, Jane; Carline, Jan D; Durning, Steven J

2016-05-01

The authors of this article reviewed the methodology of three common consensus methods: nominal group process, consensus development panels, and the Delphi technique. The authors set out to determine how a majority of researchers are conducting these studies, how they are analyzing results, and subsequently the manner in which they are reporting their findings. The authors conclude with a set of guidelines and suggestions designed to aid researchers who choose to use the consensus methodology in their work.Overall, researchers need to describe their inclusion criteria. In addition to this, on the basis of the current literature the authors found that a panel size of 5 to 11 members was most beneficial across all consensus methods described. Lastly, the authors agreed that the statistical analyses done in consensus method studies should be as rigorous as possible and that the predetermined definition of consensus must be included in the ultimate manuscript. More specific recommendations are given for each of the three consensus methods described in the article.

Consensus on Intermediate Scale Salt Field Test Design

Energy Technology Data Exchange (ETDEWEB)

Kuhlman, Kristopher L; Mills, Melissa Marie; Matteo, Edward N

2017-03-01

This report summarizes the first stage in a collaborative effort by Sandia, Los Alamos, and Lawrence Berkeley National Laboratories to design a small-diameter borehole heater test in salt at the Waste Isolation Pilot Plant (WIPP) for the US Department of Energy Office of Nuclear Energy (DOE-NE). The intention is to complete test design during the remainder of fiscal year 2017 (FY17), and the implementation of the test will begin in FY18. This document is the result of regular meetings between the three national labs and the DOE-NE, and is intended to represent a consensus of these meetings and discussions.

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.

Delay-Induced Consensus and Quasi-Consensus in Multi-Agent Dynamical Systems

NARCIS (Netherlands)

Yu, Wenwu; Chen, Guanrong; Cao, Ming; Ren, Wei

2013-01-01

This paper studies consensus and quasi-consensus in multi-agent dynamical systems. A linear consensus protocol in the second-order dynamics is designed where both the current and delayed position information is utilized. Time delay, in a common perspective, can induce periodic oscillations or even

Binary phase solid-state photopolymerization of acrylates: design, characterization and biomineralization of 3D scaffolds for tissue engineering

Science.gov (United States)

Maitlo, Inamullah; Ali, Safdar; Akram, Muhammad Yasir; Shehzad, Farooq Khurum; Nie, Jun

2017-12-01

Porous polymer scaffolds designed by the cryogel method are attractive materials for a range of tissue engineering applications. However, the use of toxic crosslinker for retaining the pore structure limits their clinical applications. In this research, acrylates (HEA/PEGDA, HEMA/PEGDA and PEGDA) were used in the low-temperature solid-state photopolymerization to produce porous scaffolds with good structural retention. The morphology, pore diameter, mineral deposition and water absorption of the scaffold were characterized by SEM and water absorption test respectively. Elemental analysis and cytotoxicity of the biomineralized scaffold were revealed by using XRD and MTT assay test. The PEGDA-derived scaffold showed good water absorption ability and a higher degree of porosity with larger pore size compared to others. XRD patterns and IR results confirmed the formation of hydroxyapatite crystals from an alternative socking process. The overall cell proliferation was excellent, where PEGDA-derived scaffold had the highest and the most uniform cell growth, while HEMA/PEGDA scaffold showed the least. These results suggest that the cell proliferation and adhesion are directly proportional to the pore size, the shape and the porosity of scaffolds.

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.

The Effect of Structural Design on Mechanical Properties and Cellular Response of Additive Manufactured Titanium Scaffolds

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Jan Wieding

2012-08-01

Full Text Available Restoration of segmental defects in long bones remains a challenging task in orthopedic surgery. Although autologous bone is still the ‘Gold Standard’ because of its high biocompatibility, it has nevertheless been associated with several disadvantages. Consequently, artificial materials, such as calcium phosphate and titanium, have been considered for the treatment of bone defects. In the present study, the mechanical properties of three different scaffold designs were investigated. The scaffolds were made of titanium alloy (Ti6Al4V, fabricated by means of an additive manufacturing process with defined pore geometry and porosities of approximately 70%. Two scaffolds exhibited rectangular struts, orientated in the direction of loading. The struts for the third scaffold were orientated diagonal to the load direction, and featured a circular cross-section. Material properties were calculated from stress-strain relationships under axial compression testing. In vitro cell testing was undertaken with human osteoblasts on scaffolds fabricated using the same manufacturing process. Although the scaffolds exhibited different strut geometry, the mechanical properties of ultimate compressive strength were similar (145–164 MPa and in the range of human cortical bone. Test results for elastic modulus revealed values between 3.7 and 6.7 GPa. In vitro testing demonstrated proliferation and spreading of bone cells on the scaffold surface.

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

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Francesco Guido Mangano

2015-01-01

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

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;.

Fatigue Design and Prevention in Movable Scaffolding Systems

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Coelho Hugo

2017-06-01

Full Text Available The Movable Scaffolding System (MSS is a heavy construction equipment used for casting situ of concrete bridge decks. In the past decades, MSSs have become increasingly complex and industrialized, enlarging its span ranges, incorporating auxiliary elevation machinery and increasing productivity. The tendency nowadays is for strong reutilization and the notion of MSS as a disposable or temporary structure is somehow reductive. The main structure of MSSs may be potentially exposed to fatigue, usually characterized by low number of cycles with significant stress amplitude. Fatigue may be prevented through adequate design; judicious selection of materials; demanding quality control and implementation of robust inspection and maintenance plans.

Fatigue Design and Prevention in Movable Scaffolding Systems

Science.gov (United States)

Coelho, Hugo; Torres, Alberto; Pacheco, Pedro; Moreira, Cristiano; Silva, Rute; Soares, José M.; Pinto, Dânia

2017-06-01

The Movable Scaffolding System (MSS) is a heavy construction equipment used for casting situ of concrete bridge decks. In the past decades, MSSs have become increasingly complex and industrialized, enlarging its span ranges, incorporating auxiliary elevation machinery and increasing productivity. The tendency nowadays is for strong reutilization and the notion of MSS as a disposable or temporary structure is somehow reductive. The main structure of MSSs may be potentially exposed to fatigue, usually characterized by low number of cycles with significant stress amplitude. Fatigue may be prevented through adequate design; judicious selection of materials; demanding quality control and implementation of robust inspection and maintenance plans.

PLA-poloxamer/poloxamine copolymers for ligament tissue engineering: sound macromolecular design for degradable scaffolds and MSC differentiation.

Science.gov (United States)

Leroy, Adrien; Nottelet, Benjamin; Bony, Claire; Pinese, Coline; Charlot, Benoît; Garric, Xavier; Noël, Danièle; Coudane, Jean

2015-04-01

The treatment of anterior cruciate ligament (ACL) failures remains a current clinical challenge. The present study aims at providing suitable degradable scaffolds for ligament tissue engineering. First, we focus on the design and the evaluation of poly(lactide)/poloxamer or poly(lactide)/poloxamine multiblock copolymers selected and developed to have suitable degradation and mechanical properties to match ACL repair. In the second part, it is shown that the copolymers can be processed in the form of microfibers and scaffolds consisting of a combination of twisted/braided fibers to further modulate the mechanical properties and prepare scaffold prototypes suitable for ligament application. Finally, after assessment of their cytocompatibility, the polymer scaffolds are associated with mesenchymal stem cells (MSCs). MSC differentiation toward a ligament fibroblast phenotype is promoted by a dual stimulation including an inductive culture medium and cyclic mechanical loads. RT-qPCR analyses confirm the potential of our scaffolds and MSCs for ACL regeneration with upregulation of some differentiation markers including Scleraxis, Tenascin-C and Tenomodulin.

Microstructure and compression properties of 3D powder printed Ti-6Al-4V scaffolds with designed porosity: Experimental and computational analysis

Energy Technology Data Exchange (ETDEWEB)

Barui, Srimanta; Chatterjee, Subhomoy; Mandal, Sourav [Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science, Bangalore (India); Center of Excellence and Innovation in Biotechnology-' Translational Centre on Biomaterials for Orthopaedic and Dental Applications' , Materials Research Center, Indian Institute of Science, Bangalore (India); Kumar, Alok [Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science, Bangalore (India); Basu, Bikramjit, E-mail: bikram@mrc.iisc.ernet.in [Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science, Bangalore (India); Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore (India); Center of Excellence and Innovation in Biotechnology-' Translational Centre on Biomaterials for Orthopaedic and Dental Applications' , Materials Research Center, Indian Institute of Science, Bangalore (India)

2017-01-01

The osseointegration of metallic implants depends on an effective balance among designed porosity to facilitate angiogenesis, tissue in-growth and bone-mimicking elastic modulus with good strength properties. While addressing such twin requirements, the present study demonstrates a low temperature additive manufacturing based processing strategy to fabricate Ti-6Al-4V scaffolds with designed porosity using inkjet-based 3D powder printing (3DPP). A novel starch-based aqueous binder was prepared and the physico-chemical parameters such as pH, viscosity, and surface tension were optimized for drop-on-demand (DOD) based thermal inkjet printing. Micro-computed tomography (micro-CT) of sintered scaffolds revealed a 57% total porosity in homogeneously porous scaffold and 45% in the gradient porous scaffold with 99% interconnectivity among the micropores. Under uniaxial compression testing, the strength of homogeneously porous and gradient porous scaffolds were ~ 47 MPa and ~ 90 MPa, respectively. The progressive failure in homogeneously porous scaffold was recorded. In parallel to experimental measurements, finite element (FE) analyses have been performed to study the stress distribution globally and also locally around the designed pores. Consistent with FE analyses, a higher elastic modulus was recorded with gradient porous scaffolds (~ 3 GPa) than the homogenously porous scaffolds (~ 2 GPa). While comparing with the existing literature reports, the present work, for the first time, establishes ‘direct powder printing methodology’ of Ti-6Al-4V porous scaffolds with biomedically relevant microstructural and mechanical properties. Also, a new FE analysis approach, based on the critical understanding of the porous architecture using micro-CT results, is presented to realistically predict the compression response of porous scaffolds. - Highlights: • Binder physics and process parameters in inkjet 3D printing of Ti-6Al-4V • Phase assembly and detailed microstructure

Microstructure and compression properties of 3D powder printed Ti-6Al-4V scaffolds with designed porosity: Experimental and computational analysis

International Nuclear Information System (INIS)

Barui, Srimanta; Chatterjee, Subhomoy; Mandal, Sourav; Kumar, Alok; Basu, Bikramjit

2017-01-01

The osseointegration of metallic implants depends on an effective balance among designed porosity to facilitate angiogenesis, tissue in-growth and bone-mimicking elastic modulus with good strength properties. While addressing such twin requirements, the present study demonstrates a low temperature additive manufacturing based processing strategy to fabricate Ti-6Al-4V scaffolds with designed porosity using inkjet-based 3D powder printing (3DPP). A novel starch-based aqueous binder was prepared and the physico-chemical parameters such as pH, viscosity, and surface tension were optimized for drop-on-demand (DOD) based thermal inkjet printing. Micro-computed tomography (micro-CT) of sintered scaffolds revealed a 57% total porosity in homogeneously porous scaffold and 45% in the gradient porous scaffold with 99% interconnectivity among the micropores. Under uniaxial compression testing, the strength of homogeneously porous and gradient porous scaffolds were ~ 47 MPa and ~ 90 MPa, respectively. The progressive failure in homogeneously porous scaffold was recorded. In parallel to experimental measurements, finite element (FE) analyses have been performed to study the stress distribution globally and also locally around the designed pores. Consistent with FE analyses, a higher elastic modulus was recorded with gradient porous scaffolds (~ 3 GPa) than the homogenously porous scaffolds (~ 2 GPa). While comparing with the existing literature reports, the present work, for the first time, establishes ‘direct powder printing methodology’ of Ti-6Al-4V porous scaffolds with biomedically relevant microstructural and mechanical properties. Also, a new FE analysis approach, based on the critical understanding of the porous architecture using micro-CT results, is presented to realistically predict the compression response of porous scaffolds. - Highlights: • Binder physics and process parameters in inkjet 3D printing of Ti-6Al-4V • Phase assembly and detailed microstructure

Design and properties of 3D scaffolds for bone tissue engineering.

Science.gov (United States)

Gómez, S; Vlad, M D; López, J; Fernández, E

2016-09-15

In this study, the Voronoi tessellation method has been used to design novel bone like three dimension (3D) porous scaffolds. The Voronoi method has been processed with computer design software to obtain 3D virtual isotropic porous interconnected models, exactly matching the main histomorphometric indices of trabecular bone (trabecular thickness, trabecular separation, trabecular number, bone volume to total volume ratio, bone surface to bone volume ratio, etc.). These bone like models have been further computed for mechanical (elastic modulus) and fluid mass transport (permeability) properties. The results show that the final properties of the scaffolds can be controlled during their microstructure and histomorphometric initial design stage. It is also shown that final properties can be tuned during the design stage to exactly match those of trabecular natural bone. Moreover, identical total porosity models can be designed with quite different specific bone surface area and thus, this specific microstructural feature can be used to favour cell adhesion, migration and, ultimately, new bone apposition (i.e. osteoconduction). Once the virtual models are fully characterized and optimized, these can be easily 3D printed by additive manufacturing and/or stereolitography technologies. The significance of this article goes far beyond the specific objectives on which it is focussed. In fact, it shows, in a guided way, the entire novel process that can be followed to design graded porous implants, whatever its external shape and geometry, but internally tuned to the exact histomorphometric indices needed to match natural human tissues microstructures and, consequently, their mechanical and fluid properties, among others. The significance is even more relevant nowadays thanks to the available new computing and design software that is easily linked to the 3D printing new technologies. It is this transversality, at the frontier of different disciplines, the main characteristic

Design and characterization of a biodegradable double-layer scaffold aimed at periodontal tissue-engineering applications.

Science.gov (United States)

Requicha, João F; Viegas, Carlos A; Hede, Shantesh; Leonor, Isabel B; Reis, Rui L; Gomes, Manuela E

2016-05-01

The inefficacy of the currently used therapies in achieving the regeneration ad integrum of the periodontium stimulates the search for alternative approaches, such as tissue-engineering strategies. Therefore, the core objective of this study was to develop a biodegradable double-layer scaffold for periodontal tissue engineering. The design philosophy was based on a double-layered construct obtained from a blend of starch and poly-ε-caprolactone (30:70 wt%; SPCL). A SPCL fibre mesh functionalized with silanol groups to promote osteogenesis was combined with a SPCL solvent casting membrane aiming at acting as a barrier against the migration of gingival epithelium into the periodontal defect. Each layer of the double-layer scaffolds was characterized in terms of morphology, surface chemical composition, degradation behaviour and mechanical properties. Moreover, the behaviour of seeded/cultured canine adipose-derived stem cells (cASCs) was assessed. In general, the developed double-layered scaffolds demonstrated adequate degradation and mechanical behaviour for the target application. Furthermore, the biological assays revealed that both layers of the scaffold allow adhesion and proliferation of the seeded undifferentiated cASCs, and the incorporation of silanol groups into the fibre-mesh layer enhance the expression of a typical osteogenic marker. This study allowed an innovative construct to be developed, combining a three-dimensional (3D) scaffold with osteoconductive properties and with potential to assist periodontal regeneration, carrying new possible solutions to current clinical needs. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Mechanical anisotropy of titanium scaffolds

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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.

Designing and Implementing Web-Based Scaffolding Tools for Technology-Enhanced Socioscientific Inquiry

Science.gov (United States)

Shin, Suhkyung; Brush, Thomas A.; Glazewski, Krista D.

2017-01-01

This study explores how web-based scaffolding tools provide instructional support while implementing a socio-scientific inquiry (SSI) unit in a science classroom. This case study focused on how students used web-based scaffolding tools during SSI activities, and how students perceived the SSI unit and the scaffolding tools embedded in the SSI…

Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

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Baichuan Wang

2014-01-01

Full Text Available Designer self-assembling peptide nanofiber hydrogel scaffolds have been considered as promising biomaterials for tissue engineering because of their excellent biocompatibility and biofunctionality. Our previous studies have shown that a novel designer functionalized self-assembling peptide nanofiber hydrogel scaffold (RLN/RADA16, LN-NS containing N-terminal peptide sequence of link protein (link N can promote nucleus pulposus cells (NPCs adhesion and three-dimensional (3D migration and stimulate biosynthesis of type II collagen and aggrecan by NPCs in vitro. The present study has extended these investigations to determine the effects of this functionalized LN-NS on bone marrow stem cells (BMSCs, a potential cell source for NP regeneration. Although the functionalized LN-NS cannot promote BMSCs proliferation, it significantly promotes BMSCs adhesion compared with that of the pure RADA16 hydrogel scaffold. Moreover, the functionalized LN-NS remarkably stimulates biosynthesis and deposition of type II collagen and aggrecan. These data demonstrate that the functionalized peptide nanofiber hydrogel scaffold containing link N peptide as a potential matrix substrate will be very useful in the NP tissue regeneration.

Alginate/nanohydroxyapatite scaffolds with designed core/shell structures fabricated by 3D plotting and in situ mineralization for bone tissue engineering.

Science.gov (United States)

Luo, Yongxiang; Lode, Anja; Wu, Chengtie; Chang, Jiang; Gelinsky, Michael

2015-04-01

Composite scaffolds, especially polymer/hydroxyapatite (HAP) composite scaffolds with predesigned structures, are promising materials for bone tissue engineering. Various methods including direct mixing of HAP powder with polymers or incubating polymer scaffolds in simulated body fluid for preparing polymer/HAP composite scaffolds are either uncontrolled or require long times of incubation. In this work, alginate/nano-HAP composite scaffolds with designed pore parameters and core/shell structures were fabricated using 3D plotting technique and in situ mineralization under mild conditions (at room temperature and without the use of any organic solvents). Light microscopy, scanning electron microscopy, microcomputer tomography, X-ray diffraction, and Fourier transform infrared spectroscopy were applied to characterize the fabricated scaffolds. Mechanical properties and protein delivery of the scaffolds were evaluated, as well as the cell response to the scaffolds by culturing human bone-marrow-derived mesenchymal stem cells (hBMSC). The obtained data indicate that this method is suitable to fabricate alginate/nano-HAP composite scaffolds with a layer of nano-HAP, coating the surface of the alginate strands homogeneously and completely. The surface mineralization enhanced the mechanical properties and improved the cell attachment and spreading, as well as supported sustaining protein release, compared to pure alginate scaffolds without nano-HAP shell layer. The results demonstrated that the method provides an interesting option for bone tissue engineering application.

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.

Preliminary In Vitro Assessment of Stem Cell Compatibility with Cross-Linked Poly(ε-caprolactone urethane Scaffolds Designed through High Internal Phase Emulsions

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Sylvie Changotade

2015-01-01

Full Text Available By using a high internal phase emulsion process, elastomeric poly(ε-caprolactone urethane (PCLU scaffolds were designed with pores size ranging from below 150 μm to 1800 μm and a porosity of 86% making them suitable for bone tissue engineering applications. Moreover, the pores appeared to be excellently interconnected, promoting cellularization and future bone ingrowth. This study evaluated the in vitro cytotoxicity of the PCLU scaffolds towards human mesenchymal stem cells (hMSCs through the evaluation of cell viability and metabolic activity during extract test and indirect contact test at the beginning of the scaffold lifetime. Both tests demonstrated that PCLU scaffolds did not induce any cytotoxic response. Finally, direct interaction of hMSCs and PCLU scaffolds showed that PCLU scaffolds were suitable for supporting the hMSCs adhesion and that the cells were well spread over the pore walls. We conclude that PCLU scaffolds may be a good candidate for bone tissue regeneration applications using hMSCs.

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.

Consensus Control Design for 360 MN Extrusion Machine Producing Process

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Chao Wang

2014-01-01

Full Text Available This paper mainly addresses the issue of 360 MN extrusion machine and focuses on the stabilization control of main table attitude. We will first introduce the problem and then model the extrusion machine. As the machine is a multi-input multioutput (MIMO and strong coupling system, it is challenging to apply existing control theory to design a controller to stabilize the main table attitude. Motivated by recent research in the field of multiagent systems, we design a consensus control protocol for our system and derive our convergence conditions based directly on Routh stability criterion. The advantages of the design are also demonstrated by numerical simulation.

Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering.

Science.gov (United States)

Denry, Isabelle; Kuhn, Liisa T

2016-01-01

Our goal is to review design strategies for the fabrication of calcium phosphate ceramic scaffolds (CPS), in light of their transient role in bone tissue engineering and associated requirements for effective bone regeneration. We examine the various design options available to meet mechanical and biological requirements of CPS and later focus on the importance of proper characterization of CPS in terms of architecture, mechanical properties and time-sensitive properties such as biodegradability. Finally, relationships between in vitro versus in vivo testing are addressed, with an attempt to highlight reliable performance predictors. A combinatory design strategy should be used with CPS, taking into consideration 3D architecture, adequate surface chemistry and topography, all of which are needed to promote bone formation. CPS represent the media of choice for delivery of osteogenic factors and anti-infectives. Non-osteoblast mediated mineral deposition can confound in vitro osteogenesis testing of CPS and therefore the expression of a variety of proteins or genes including collagen type I, bone sialoprotein and osteocalcin should be confirmed in addition to increased mineral content. CPS are a superior scaffold material for bone regeneration because they actively promote osteogenesis. Biodegradability of CPS via calcium and phosphate release represents a unique asset. Structural control of CPS at the macro, micro and nanoscale and their combination with cells and polymeric materials is likely to lead to significant developments in bone tissue engineering. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

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

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.

Design of a hybrid biomaterial for tissue engineering: Biopolymer-scaffold integrated with an autologous hydrogel carrying mesenchymal stem-cells.

Science.gov (United States)

Weinstein-Oppenheimer, Caroline R; Brown, Donald I; Coloma, Rodrigo; Morales, Patricio; Reyna-Jeldes, Mauricio; Díaz, María J; Sánchez, Elizabeth; Acevedo, Cristian A

2017-10-01

Biologically active biomaterials as biopolymers and hydrogels have been used in medical applications providing favorable results in tissue engineering. In this research, a wound dressing device was designed by integration of an autologous clot hydrogel carrying mesenchymal stem-cells onto a biopolymeric scaffold. This hybrid biomaterial was tested in-vitro and in-vivo, and used in a human clinical case. The biopolymeric scaffold was made with gelatin, chitosan and hyaluronic acid, using a freeze-drying method. The scaffold was a porous material which was designed evaluating both physical properties (glass transition, melting temperature and pore size) and biological properties (cell viability and fibronectin expression). Two types of chitosan (120 and 300kDa) were used to manufacture the scaffold, being the high molecular weight the most biologically active and stable after sterilization with gamma irradiation (25kGy). A clot hydrogel was formulated with autologous plasma and calcium chloride, using an approach based on design of experiments. The optimum hydrogel was used to incorporate cells onto the porous scaffold, forming a wound dressing biomaterial. The wound dressing device was firstly tested in-vitro using human cells, and then, its biosecurity was evaluated in-vivo using a rabbit model. The in-vitro results showed high cell viability after one week (99.5%), high mitotic index (19.8%) and high fibronectin expression. The in-vivo application to rabbits showed adequate biodegradability capacity (between 1 and 2weeks), and the histological evaluation confirmed absence of rejection signs and reepithelization on the wound zone. Finally, the wound dressing biomaterial was used in a single human case to implant autologous cells on a skin surgery. The medical examination indicated high biocompatibility, partial biodegradation at one week, early regeneration capacity at 4weeks and absence of rejection signs. Copyright © 2017 Elsevier B.V. All rights reserved.

Establishment of Kansei Database and Application to Design for Consensus Building

Science.gov (United States)

Yasuda, Keiichi; Shiraki, Wataru

Reflecting the recent social background where the importance of bridge landscape design is recognized and the new business style of citizen-involved infrastructure development has started, there has been a growing need of design where aesthetic feeling of actual users is reflected. In this research, a focus has been placed on the Kansei engineering technique where users' needs are reflected on product development. A questionnaire survey has been conducted for bridge engineers who are most intensively involved in design work and students as actual users. The result was analyzed by factor analysis and the Hayashi's quantification methods (category I). A tool required at consensus-building occasions has been created to change design elements and display accompanying evaluation difference while using the Kansei database.

Geometric and mechanical properties evaluation of scaffolds for bone tissue applications designing by a reaction-diffusion models and manufactured with a material jetting system

Directory of Open Access Journals (Sweden)

Marco A. Velasco

2016-10-01

Full Text Available Scaffolds are essential in bone tissue engineering, as they provide support to cells and growth factors necessary to regenerate tissue. In addition, they meet the mechanical function of the bone while it regenerates. Currently, the multiple methods for designing and manufacturing scaffolds are based on regular structures from a unit cell that repeats in a given domain. However, these methods do not resemble the actual structure of the trabecular bone which may work against osseous tissue regeneration. To explore the design of porous structures with similar mechanical properties to native bone, a geometric generation scheme from a reaction-diffusion model and its manufacturing via a material jetting system is proposed. This article presents the methodology used, the geometric characteristics and the modulus of elasticity of the scaffolds designed and manufactured. The method proposed shows its potential to generate structures that allow to control the basic scaffold properties for bone tissue engineering such as the width of the channels and porosity. The mechanical properties of our scaffolds are similar to trabecular tissue present in vertebrae and tibia bones. Tests on the manufactured scaffolds show that it is necessary to consider the orientation of the object relative to the printing system because the channel geometry, mechanical properties and roughness are heavily influenced by the position of the surface analyzed with respect to the printing axis. A possible line for future work may be the establishment of a set of guidelines to consider the effects of manufacturing processes in designing stages.

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.

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.

What is the teachers’ role when students learn through design of learning games in a scaffolded gamified learning environment?

DEFF Research Database (Denmark)

Weitze, Charlotte Lærke

The aim of this research project is to create a reusable and flexible gamified learning design where the students are learning subject matters through the design of digital learning games. The students are their own learning designers forming teams that create games. The teams also peer review...... how the use of pre-build learning games in education can be taken a step further into the building of learning games while implementing subject matters from curriculum, not only focussing on the creative game design process. The aim of the form of this learning design is to scaffold the novice....../ play test each others games as a way to qualify the learning taking place around as well as inside the games they are building. The discussion is focusing on how the chosen pedagogical approach is framed within the gamified environment as well as on how the teachers can guide and scaffold the learning...

Three-dimensional dynamic fabrication of engineered cartilage based on chitosan/gelatin hybrid hydrogel scaffold in a spinner flask with a special designed steel frame

International Nuclear Information System (INIS)

Song, Kedong; Li, Liying; Li, Wenfang; Zhu, Yanxia; Jiao, Zeren; Lim, Mayasari; Fang, Meiyun; Shi, Fangxin; Wang, Ling; Liu, Tianqing

2015-01-01

Cartilage transplantation using in vitro tissue engineered cartilage is considered a promising treatment for articular cartilage defects. In this study, we assessed the advantages of adipose derived stem cells (ADSCs) combined with chitosan/gelatin hybrid hydrogel scaffolds, which acted as a cartilage biomimetic scaffold, to fabricate a tissue engineered cartilage dynamically in vitro and compared this with traditional static culture. Physical properties of the hydrogel scaffolds were evaluated and ADSCs were inoculated into the hydrogel at a density of 1 × 10 7 cells/mL and cultured in a spinner flask with a special designed steel framework and feed with chondrogenic inductive media for two weeks. The results showed that the average pore size, porosity, swelling rate and elasticity modulus of hybrid scaffolds with good biocompatibility were 118.25 ± 19.51 μm, 82.60 ± 2.34%, 361.28 ± 0.47% and 61.2 ± 0.16 kPa, respectively. ADSCs grew well in chitosan/gelatin hybrid scaffold and successfully differentiated into chondrocytes, showing that the scaffolds were suitable for tissue engineering applications in cartilage regeneration. Induced cells cultivated in a dynamic spinner flask with a special designed steel frame expressed more proteoglycans and the cell distribution was much more uniform with the scaffold being filled mostly with extracellular matrix produced by cells. A spinner flask with framework promoted proliferation and chondrogenic differentiation of ADSCs within chitosan/gelatin hybrid scaffolds and accelerated dynamic fabrication of cell–hydrogel constructs, which could be a selective and good method to construct tissue engineered cartilage in vitro. - Highlights: • ADSCs/hybrid scaffold constructs are dynamically fabricated in a spinner flask with a special framework. • Inside convection in spinner flask made enough supplement of oxygen and nutrients far beyond the depth of passive diffusion. • 3D culture environment accelerated mass

Three-dimensional dynamic fabrication of engineered cartilage based on chitosan/gelatin hybrid hydrogel scaffold in a spinner flask with a special designed steel frame

Energy Technology Data Exchange (ETDEWEB)

Song, Kedong, E-mail: kedongsong@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Li, Liying; Li, Wenfang [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Zhu, Yanxia [Anti-Ageing and Regenerative Medicine Centre, Shenzhen University, 3688 Nanhai Avenue, Shenzhen 518060 Guangdong (China); Jiao, Zeren [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Lim, Mayasari [Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457 (Singapore); Fang, Meiyun [Department of Hematology, First Affiliated Hospital, Dalian Medical University, Dalian 116011 (China); Shi, Fangxin [Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Wang, Ling, E-mail: whwl@hotmail.com [Department of Obstetrics and Gynecology, First Affiliated Hospital, Dalian Medical University, Dalian 116011 (China); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China)

2015-10-01

Cartilage transplantation using in vitro tissue engineered cartilage is considered a promising treatment for articular cartilage defects. In this study, we assessed the advantages of adipose derived stem cells (ADSCs) combined with chitosan/gelatin hybrid hydrogel scaffolds, which acted as a cartilage biomimetic scaffold, to fabricate a tissue engineered cartilage dynamically in vitro and compared this with traditional static culture. Physical properties of the hydrogel scaffolds were evaluated and ADSCs were inoculated into the hydrogel at a density of 1 × 10{sup 7} cells/mL and cultured in a spinner flask with a special designed steel framework and feed with chondrogenic inductive media for two weeks. The results showed that the average pore size, porosity, swelling rate and elasticity modulus of hybrid scaffolds with good biocompatibility were 118.25 ± 19.51 μm, 82.60 ± 2.34%, 361.28 ± 0.47% and 61.2 ± 0.16 kPa, respectively. ADSCs grew well in chitosan/gelatin hybrid scaffold and successfully differentiated into chondrocytes, showing that the scaffolds were suitable for tissue engineering applications in cartilage regeneration. Induced cells cultivated in a dynamic spinner flask with a special designed steel frame expressed more proteoglycans and the cell distribution was much more uniform with the scaffold being filled mostly with extracellular matrix produced by cells. A spinner flask with framework promoted proliferation and chondrogenic differentiation of ADSCs within chitosan/gelatin hybrid scaffolds and accelerated dynamic fabrication of cell–hydrogel constructs, which could be a selective and good method to construct tissue engineered cartilage in vitro. - Highlights: • ADSCs/hybrid scaffold constructs are dynamically fabricated in a spinner flask with a special framework. • Inside convection in spinner flask made enough supplement of oxygen and nutrients far beyond the depth of passive diffusion. • 3D culture environment accelerated mass

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).

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours

NARCIS (Netherlands)

Leary, A. F.; Quinn, M.; Fujiwara, K.; Coleman, R. L.; Kohn, E.; Sugiyama, T.; Glasspool, R.; Ray-Coquard, I.; Colombo, N.; Bacon, M.; Zeimet, A.; Westermann, A.; Gomez-Garcia, E.; Provencher, D.; Welch, S.; Small, W.; Millan, D.; Okamoto, A.; Stuart, G.; Ochiai, K.

2017-01-01

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian

Channeled Scaffolds for Engineering Myocardium with Mechanical Stimulation

Science.gov (United States)

Zhang, Ting; Wan, Leo Q.; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

2011-01-01

The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) are critically important for engineering functional myocardial tissue. We report the development of chitosan-collagen scaffolds with micro-pores and an array of parallel channels (~200 μm in diameter) that were specifically designed for cardiac tissue engineering with mechanical stimulation. The scaffolds were designed to have the structural and mechanical properties similar to those of the native human heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom-designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1–2 mm thick) consisted of metabolically active cells and started to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stresses promoted cell alignment, elongation, and the expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. PMID:22081518

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.

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.

Influence of Different Three-Dimensional Open Porous Titanium Scaffold Designs on Human Osteoblasts Behavior in Static and Dynamic Cell Investigations

Directory of Open Access Journals (Sweden)

Jana Markhoff

2015-08-01

Full Text Available In the treatment of osseous defects micro-structured three-dimensional materials for bone replacement serve as leading structure for cell migration, proliferation and bone formation. The scaffold design and culture conditions are crucial for the limited diffusion distance of nutrients and oxygen. In static culture, decreased cell activity and irregular distribution occur within the scaffold. Dynamic conditions entail physical stimulation and constant medium perfusion imitating physiological nutrient supply and metabolite disposal. Therefore, we investigated the influence of different scaffold configurations and cultivation methods on human osteoblasts. Cells were seeded on three-dimensional porous Ti-6Al-4V scaffolds manufactured with selective laser melting (SLM or electron beam melting (EBM varying in porosity, pore size and basic structure (cubic, diagonal, pyramidal and cultured under static and dynamic conditions. Cell viability, migration and matrix production were examined via mitochondrial activity assay, fluorescence staining and ELISA. All scaffolds showed an increasing cell activity and matrix production under static conditions over time. Expectations about the dynamic culture were only partially fulfilled, since it enabled proliferation alike the static one and enhanced cell migration. Overall, the SLM manufactured scaffold with the highest porosity, small pore size and pyramidal basic structure proved to be the most suitable structure for cell proliferation and migration.

Influence of Different Three-Dimensional Open Porous Titanium Scaffold Designs on Human Osteoblasts Behavior in Static and Dynamic Cell Investigations.

Science.gov (United States)

Markhoff, Jana; Wieding, Jan; Weissmann, Volker; Pasold, Juliane; Jonitz-Heincke, Anika; Bader, Rainer

2015-08-24

In the treatment of osseous defects micro-structured three-dimensional materials for bone replacement serve as leading structure for cell migration, proliferation and bone formation. The scaffold design and culture conditions are crucial for the limited diffusion distance of nutrients and oxygen. In static culture, decreased cell activity and irregular distribution occur within the scaffold. Dynamic conditions entail physical stimulation and constant medium perfusion imitating physiological nutrient supply and metabolite disposal. Therefore, we investigated the influence of different scaffold configurations and cultivation methods on human osteoblasts. Cells were seeded on three-dimensional porous Ti-6Al-4V scaffolds manufactured with selective laser melting (SLM) or electron beam melting (EBM) varying in porosity, pore size and basic structure (cubic, diagonal, pyramidal) and cultured under static and dynamic conditions. Cell viability, migration and matrix production were examined via mitochondrial activity assay, fluorescence staining and ELISA. All scaffolds showed an increasing cell activity and matrix production under static conditions over time. Expectations about the dynamic culture were only partially fulfilled, since it enabled proliferation alike the static one and enhanced cell migration. Overall, the SLM manufactured scaffold with the highest porosity, small pore size and pyramidal basic structure proved to be the most suitable structure for cell proliferation and migration.

Metacognitive Scaffolding in an Innovative Learning Arrangement

Science.gov (United States)

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

2011-01-01

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

Design of water-soluble, thiol-reactive polymers of controlled molecular weight: a novel multivalent scaffold

Science.gov (United States)

Carrillo, Alvaro; Gujraty, Kunal V.; Rai, Prakash R.; Kane, Ravi S.

2005-07-01

Multivalent molecules, i.e. scaffolds presenting multiple copies of a suitable ligand, constitute an emerging class of nanoscale therapeutics. We present a novel approach for the design of multivalent ligands, which allows the biofunctionalization of polymers with proteins or peptides in a controlled orientation. It consists of the synthesis of water-soluble, activated polymer scaffolds of controlled molecular weight, which can be biofunctionalized with various thiolated ligands in aqueous media under mild conditions. These polymers were synthesized by ring-opening metathesis polymerization (ROMP) and further modified to make them water-soluble. The incorporation of chloride groups activated the polymers to react with thiol-containing peptides or proteins, and the formation of multivalent ligands in aqueous media was demonstrated. This strategy represents a convenient route for synthesizing multivalent ligands of controlled dimensions and valency.

Edible Scaffolds Based on Non-Mammalian Biopolymers for Myoblast Growth

Directory of Open Access Journals (Sweden)

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.

Design and production of sintered β-tricalcium phosphate 3D scaffolds for bone tissue regeneration

International Nuclear Information System (INIS)

Santos, Carlos F.L.; Silva, Abílio P.; Lopes, Luís; Pires, Inês; Correia, Ilidio J.

2012-01-01

The characteristics of sintered β-tricalcium phosphate (β-TCP) scaffolds produced by 3D printing were studied by means of X-ray diffraction, Scanning Electron Microscopy, Fourier transform infrared spectroscopy, uniaxial compression tests and cytotoxicity tests, using human osteoblast cells. The results reported include details of the β-TCP scaffolds' porosity, density, phase stability, mechanical behavior and cytotoxic profile. Collectively, these properties are fundamental for the future application of these scaffolds as bone substitutes for individualized therapy. Highlights: ► β-Tricalcium phosphate (β-TCP) 3D scaffolds were produced by rapid prototyping. ► Scaffold properties were assessed by SEM, FTIR, XRD and by mechanical tests. ► The cytotoxic profile of the scaffolds was characterized by in vitro assays. ► Scaffolds have good properties for its application as bone substitutes for individualized therapy.

Channelled scaffolds for engineering myocardium with mechanical stimulation.

Science.gov (United States)

Zhang, Ting; Wan, Leo Q; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

2012-10-01

The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) of the heart are important characteristics in the engineering of functional myocardial tissue. This study reports on the development of chitosan-collagen scaffolds with micropores and an array of parallel channels (~ 200 µm in diameter) that were specifically designed for cardiac tissue engineering using mechanical stimulation. The scaffolds were designed to have similar structural and mechanical properties of those of native heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1-2 mm thick) consisted of metabolically active cells that began to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stress promoted cell alignment, elongation, and expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. Copyright © 2011 John Wiley & Sons, Ltd.

Three-dimensional dynamic fabrication of engineered cartilage based on chitosan/gelatin hybrid hydrogel scaffold in a spinner flask with a special designed steel frame.

Science.gov (United States)

Song, Kedong; Li, Liying; Li, Wenfang; Zhu, Yanxia; Jiao, Zeren; Lim, Mayasari; Fang, Meiyun; Shi, Fangxin; Wang, Ling; Liu, Tianqing

2015-10-01

Cartilage transplantation using in vitro tissue engineered cartilage is considered a promising treatment for articular cartilage defects. In this study, we assessed the advantages of adipose derived stem cells (ADSCs) combined with chitosan/gelatin hybrid hydrogel scaffolds, which acted as a cartilage biomimetic scaffold, to fabricate a tissue engineered cartilage dynamically in vitro and compared this with traditional static culture. Physical properties of the hydrogel scaffolds were evaluated and ADSCs were inoculated into the hydrogel at a density of 1×10(7) cells/mL and cultured in a spinner flask with a special designed steel framework and feed with chondrogenic inductive media for two weeks. The results showed that the average pore size, porosity, swelling rate and elasticity modulus of hybrid scaffolds with good biocompatibility were 118.25±19.51 μm, 82.60±2.34%, 361.28±0.47% and 61.2±0.16 kPa, respectively. ADSCs grew well in chitosan/gelatin hybrid scaffold and successfully differentiated into chondrocytes, showing that the scaffolds were suitable for tissue engineering applications in cartilage regeneration. Induced cells cultivated in a dynamic spinner flask with a special designed steel frame expressed more proteoglycans and the cell distribution was much more uniform with the scaffold being filled mostly with extracellular matrix produced by cells. A spinner flask with framework promoted proliferation and chondrogenic differentiation of ADSCs within chitosan/gelatin hybrid scaffolds and accelerated dynamic fabrication of cell-hydrogel constructs, which could be a selective and good method to construct tissue engineered cartilage in vitro. Copyright © 2015 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.

Enzymatically biomineralized chitosan scaffolds for tissue-engineering applications.

NARCIS (Netherlands)

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

2017-01-01

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

Design and production of sintered {beta}-tricalcium phosphate 3D scaffolds for bone tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Santos, Carlos F.L. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Silva, Abilio P. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Lopes, Luis [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Pires, Ines [Instituto de Engenharia Mecanica - Lisboa (IDMEC Lisboa/IST/UTL), Avenida Rovisco Pais, 1049-001 Lisboa (Portugal); Correia, Ilidio J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

2012-07-01

The characteristics of sintered {beta}-tricalcium phosphate ({beta}-TCP) scaffolds produced by 3D printing were studied by means of X-ray diffraction, Scanning Electron Microscopy, Fourier transform infrared spectroscopy, uniaxial compression tests and cytotoxicity tests, using human osteoblast cells. The results reported include details of the {beta}-TCP scaffolds' porosity, density, phase stability, mechanical behavior and cytotoxic profile. Collectively, these properties are fundamental for the future application of these scaffolds as bone substitutes for individualized therapy. Highlights: Black-Right-Pointing-Pointer {beta}-Tricalcium phosphate ({beta}-TCP) 3D scaffolds were produced by rapid prototyping. Black-Right-Pointing-Pointer Scaffold properties were assessed by SEM, FTIR, XRD and by mechanical tests. Black-Right-Pointing-Pointer The cytotoxic profile of the scaffolds was characterized by in vitro assays. Black-Right-Pointing-Pointer Scaffolds have good properties for its application as bone substitutes for individualized therapy.

Hydrophobicity as a design criterion for polymer scaffolds in bone tissue engineering

NARCIS (Netherlands)

Jansen, EJP; Sladek, REJ; Bahar, H; Yaffe, A; Gijbels, MJ; Kuijer, R; Bulstra, SK; Guldemond, NA; Binderman, [No Value; Koole, LH

Porous polymeric scaffolds play a key role in most tissue-engineering strategies. A series of non-degrading porous scaffolds was prepared, based on bulk-copolymerisation of 1-vinyl-2-pyrrolidinone (NVP) and n-butyl methacrylate (BMA), followed by a particulate-leaching step to generate porosity.

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

Science.gov (United States)

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

Protein Scaffolding for Small Molecule Catalysts

Energy Technology Data Exchange (ETDEWEB)

Baker, David [Univ. of Washington, Seattle, WA (United States)

2014-09-14

We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematically modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.

Introducing an attractive method for total biomimetic creation of a synthetic biodegradable bioactive bone scaffold based on statistical experimental design.

Science.gov (United States)

Shahbazi, Sara; Zamanian, Ali; Pazouki, Mohammad; Jafari, Yaser

2018-05-01

A new total biomimetic technique based on both the water uptake and degradation processes is introduced in this study to provide an interesting procedure to fabricate a bioactive and biodegradable synthetic scaffold, which has a good mechanical and structural properties. The optimization of effective parameters to scaffold fabrication was done by response surface methodology/central composite design (CCD). With this method, a synthetic scaffold was fabricated which has a uniform and open-interconnected porous structure with the largest pore size of 100-200μm. The obtained compressive ultimate strength of ~35MPa and compression modulus of 58MPa are similar to some of the trabecular bone. The pore morphology, size, and distribution of the scaffold were characterized using a scanning electron microscope and mercury porosimeter. Fourier transform infrared spectroscopy, EDAX and X-ray diffraction analyses were used to determine the chemical composition, Ca/P element ratio of mineralized microparticles, and the crystal structure of the scaffolds, respectively. The optimum biodegradable synthetic scaffold based on its raw materials of polypropylene fumarate, hydroxyethyl methacrylate and nano bioactive glass (PPF/HEMA/nanoBG) as 70/30wt/wt%, 20wt%, and 1.5wt/wt% (PHB.732/1.5) with desired porosity, pore size, and geometry were created by 4weeks immersion in SBF. This scaffold showed considerable biocompatibility in the ranging from 86 to 101% for the indirect and direct contact tests and good osteoblast cell attachment when studied with the bone-like cells. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

Science.gov (United States)

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

2015-11-04

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

Design Thinking and Metacognitive Reflective Scaffolds: A Graphic Design-Industrial Design Transfer Case Study

Science.gov (United States)

Lee, Chien-Sing; Wong, Kuok-Shoong Daniel

2015-01-01

Scaffolding is crucial as transfer of learning does not occur naturally and teaching-learning strategies found to be effective for experts may not be suitably adopted as is for novice learners. Furthermore, opportunities are often "found" or "made." The quality of solutions, however, is mediated by different conceptualizations…

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

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

Science.gov (United States)

Zakhem, Elie; Bitar, Khalil N

2015-10-13

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

Designing of Collagen Based Poly(3-hydroxybutyrate-co-4-hydroxybutyrate Scaffolds for Tissue Engineering

Directory of Open Access Journals (Sweden)

S. Vigneswari

2015-01-01

Full Text Available P(3HB-co-4HB copolymer was modified using collagen by adapting dual solvent system. The surface properties of samples were characterized by Fourier transform infrared spectroscopy (FTIR, scanning electron microscopy (SEM, organic elemental analysis (CHN analysis, and water contact angle measurements. The effects of collagen concentration, scaffold thickness, and 4HB molar fraction on the hydrophilicity were optimized by the Taguchi method. The orthogonal array experiment was conducted to obtain the response for a hydrophilic scaffold. Analysis of variance (ANOVA was used to determine the significant parameters and determine the optimal level for each parameter. The results also showed that the hydrophilicity of P(3HB-co-4HB/collagen blend scaffolds increased as the collagen concentration increased up to 15 wt% with a molar fraction of 50 mol% at 0.1 mm scaffold thickness. The biocompatibility of the P(3HB-co-4HB/collagen blend surface was evaluated by fibroblast cell (L929 culture. The collagen blend scaffold surfaces showed significant cell adhesion and growth as compared to P(3HB-co-4HB copolymer scaffolds.

Porous titanium scaffolds fabricated using a rapid prototyping and powder metallurgy technique.

Science.gov (United States)

Ryan, Garrett E; Pandit, Abhay S; Apatsidis, Dimitrios P

2008-09-01

One of the main issues in orthopaedic implant design is the fabrication of scaffolds that closely mimic the biomechanical properties of the surrounding bone. This research reports on a multi-stage rapid prototyping technique that was successfully developed to produce porous titanium scaffolds with fully interconnected pore networks and reproducible porosity and pore size. The scaffolds' porous characteristics were governed by a sacrificial wax template, fabricated using a commercial 3D-printer. Powder metallurgy processes were employed to generate the titanium scaffolds by filling around the wax template with titanium slurry. In the attempt to optimise the powder metallurgy technique, variations in slurry concentration, compaction pressure and sintering temperature were investigated. By altering the wax design template, pore sizes ranging from 200 to 400 microm were achieved. Scaffolds with porosities of 66.8 +/- 3.6% revealed compression strengths of 104.4+/-22.5 MPa in the axial direction and 23.5 +/- 9.6 MPa in the transverse direction demonstrating their anisotropic nature. Scaffold topography was characterised using scanning electron microscopy and microcomputed tomography. Three-dimensional reconstruction enabled the main architectural parameters such as pore size, interconnecting porosity, level of anisotropy and level of structural disorder to be determined. The titanium scaffolds were compared to their intended designs, as governed by their sacrificial wax templates. Although discrepancies in architectural parameters existed between the intended and the actual scaffolds, overall the results indicate that the porous titanium scaffolds have the properties to be potentially employed in orthopaedic applications.

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)

Braided and Stacked Electrospun Nanofibrous Scaffolds for Tendon and Ligament Tissue Engineering.

Science.gov (United States)

Rothrauff, Benjamin B; Lauro, Brian B; Yang, Guang; Debski, Richard E; Musahl, Volker; Tuan, Rocky S

2017-05-01

Tendon and ligament injuries are a persistent orthopedic challenge given their poor innate healing capacity. Nonwoven electrospun nanofibrous scaffolds composed of polyesters have been used to mimic the mechanics and topographical cues of native tendons and ligaments. However, nonwoven nanofibers have several limitations that prevent broader clinical application, including poor cell infiltration, as well as tensile and suture-retention strengths that are inferior to native tissues. In this study, multilayered scaffolds of aligned electrospun nanofibers of two designs-stacked or braided-were fabricated. Mechanical properties, including structural and mechanical properties and suture-retention strength, were determined using acellular scaffolds. Human bone marrow-derived mesenchymal stem cells (MSCs) were seeded on scaffolds for up to 28 days, and assays for tenogenic differentiation, histology, and biochemical composition were performed. Braided scaffolds exhibited improved tensile and suture-retention strengths, but reduced moduli. Both scaffold designs supported expression of tenogenic markers, although the effect was greater on braided scaffolds. Conversely, cell infiltration was superior in stacked constructs, resulting in enhanced cell number, total collagen content, and total sulfated glycosaminoglycan content. However, when normalized against cell number, both designs modulated extracellular matrix protein deposition to a similar degree. Taken together, this study demonstrates that multilayered scaffolds of aligned electrospun nanofibers supported tenogenic differentiation of seeded MSCs, but the macroarchitecture is an important consideration for applications of tendon and ligament tissue engineering.

Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing

International Nuclear Information System (INIS)

Whatley, Benjamin R; Kuo, Jonathan; Shuai, Cijun; Wen Xuejun; Damon, Brooke J

2011-01-01

A custom-designed three-dimensional additive manufacturing device was developed to fabricate scaffolds for intervertebral disk (IVD) regeneration. This technique integrated a computer with a device capable of 3D movement allowing for precise motion and control over the polymer scaffold resolution. IVD scaffold structures were designed using computer-aided design to resemble the natural IVD structure. Degradable polyurethane (PU) was used as an elastic scaffold construct to mimic the elastic nature of the native IVD tissue and was deposited at a controlled rate using ultra-fine micropipettes connected to a syringe pump. The elastic PU was extruded directly onto a collecting substrate placed on a freezing stage. The three-dimensional movement of the computer-controlled device combined with the freezing stage enabled precise control of polymer deposition using extrusion. The addition of the freezing stage increased the polymer solution viscosity and hardened the polymer solution as it was extruded out of the micropipette tip. This technique created scaffolds with excellent control over macro- and micro-structure to influence cell behavior, specifically for cell adhesion, proliferation, and alignment. Concentric lamellae were printed at a high resolution to mimic the native shape and structure of the IVD. Seeded cells aligned along the concentric lamellae and acquired cell morphology similar to native tissue in the outer portion of the IVD. The fabricated scaffolds exhibited elastic behavior during compressive and shear testing, proving that the scaffolds could support loads with proper fatigue resistance without permanent deformation. Additionally, the mechanical properties of the scaffolds were comparable to those of native IVD tissue.

Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing.

Science.gov (United States)

Whatley, Benjamin R; Kuo, Jonathan; Shuai, Cijun; Damon, Brooke J; Wen, Xuejun

2011-03-01

A custom-designed three-dimensional additive manufacturing device was developed to fabricate scaffolds for intervertebral disk (IVD) regeneration. This technique integrated a computer with a device capable of 3D movement allowing for precise motion and control over the polymer scaffold resolution. IVD scaffold structures were designed using computer-aided design to resemble the natural IVD structure. Degradable polyurethane (PU) was used as an elastic scaffold construct to mimic the elastic nature of the native IVD tissue and was deposited at a controlled rate using ultra-fine micropipettes connected to a syringe pump. The elastic PU was extruded directly onto a collecting substrate placed on a freezing stage. The three-dimensional movement of the computer-controlled device combined with the freezing stage enabled precise control of polymer deposition using extrusion. The addition of the freezing stage increased the polymer solution viscosity and hardened the polymer solution as it was extruded out of the micropipette tip. This technique created scaffolds with excellent control over macro- and micro-structure to influence cell behavior, specifically for cell adhesion, proliferation, and alignment. Concentric lamellae were printed at a high resolution to mimic the native shape and structure of the IVD. Seeded cells aligned along the concentric lamellae and acquired cell morphology similar to native tissue in the outer portion of the IVD. The fabricated scaffolds exhibited elastic behavior during compressive and shear testing, proving that the scaffolds could support loads with proper fatigue resistance without permanent deformation. Additionally, the mechanical properties of the scaffolds were comparable to those of native IVD tissue.

Two-photon polymerization technique for microfabrication of CAD-designed 3D scaffolds from commercially available photosensitive materials.

Science.gov (United States)

Ovsianikov, Aleksandr; Schlie, Sabrina; Ngezahayo, Anaclet; Haverich, Axel; Chichkov, Boris N

2007-01-01

We report on recent advances in the fabrication of three-dimensional (3D) scaffolds for tissue engineering and regenerative medicine constructs using a two-photon polymerization technique (2PP). 2PP is a novel CAD/CAM technology allowing the fabrication of any computer-designed 3D structure from a photosensitive polymeric material. The flexibility of this technology and the ability to precisely define 3D construct geometry allows issues associated with vascularization and patient-specific tissue fabrication to be directly addressed. The fabrication of reproducible scaffold structures by 2PP is important for systematic studies of cellular processes and better understanding of in vitro tissue formation. In this study, 2PP was applied for the generation of 3D scaffold-like structures, using the photosensitive organic-inorganic hybrid polymer ORMOCER (ORganically MOdified CERamics) and epoxy-based SU8 materials. By comparing the proliferation rates of cells grown on flat material surfaces and under control conditions, it was demonstrated that ORMOCER and SU8 are not cytotoxic. Additional tests show that the DNA strand breaking of GFSHR-17 granulosa cells was not affected by the presence of ORMOCER. Furthermore, gap junction conductance measurements revealed that ORMOCER did not alter the formation of cell-cell junctions, critical for functional tissue growth. The possibilities of seeding 3D structures with cells were analysed. These studies demonstrate the great potential of 2PP technique for the manufacturing of scaffolds with controlled topology and properties.

Stabilizing IkappaBalpha by "consensus" design.

Science.gov (United States)

Ferreiro, Diego U; Cervantes, Carla F; Truhlar, Stephanie M E; Cho, Samuel S; Wolynes, Peter G; Komives, Elizabeth A

2007-01-26

IkappaBalpha is the major regulator of transcription factor NF-kappaB function. The ankyrin repeat region of IkappaBalpha mediates specific interactions with NF-kappaB dimers, but ankyrin repeats 1, 5 and 6 display a highly dynamic character when not in complex with NF-kappaB. Using chemical denaturation, we show here that IkappaBalpha displays two folding transitions: a non-cooperative conversion under weak perturbation, and a major cooperative folding phase upon stronger insult. Taking advantage of a native Trp residue in ankyrin repeat (AR) 6 and engineered Trp residues in AR2, AR4 and AR5, we show that the cooperative transition involves AR2 and AR3, while the non-cooperative transition involves AR5 and AR6. The major structural transition can be affected by single amino acid substitutions converging to the "consensus" ankyrin repeat sequence, increasing the native state stability significantly. We further characterized the structural and dynamic properties of the native state ensemble of IkappaBalpha and the stabilized mutants by H/(2)H exchange mass spectrometry and NMR. The solution experiments were complemented with molecular dynamics simulations to elucidate the microscopic origins of the stabilizing effect of the consensus substitutions, which can be traced to the fast conformational dynamics of the folded ensemble.

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.

Fatigue behaviour of NiTi shape memory alloy scaffolds produced by SLM, a unit cell design comparison.

Science.gov (United States)

Speirs, M; Van Hooreweder, B; Van Humbeeck, J; Kruth, J-P

2017-06-01

Selective laser melting (SLM) is an additive manufacturing technique able to produce complex functional parts via successively melting layers of metal powder. This process grants the freedom to design highly complex scaffold components to allow bone ingrowth and aid mechanical anchorage. This paper investigates the compression fatigue behaviour of three different unit cells (octahedron, cellular gyroid and sheet gyroid) of SLM nitinol scaffolds. It was found that triply periodic minimal surfaces display superior static mechanical properties in comparison to conventional octahedron beam lattice structures at identical volume fractions. Fatigue resistance was also found to be highly geometry dependent due to the effects of AM processing techniques on the surface topography and notch sensitivity. Geometries minimising nodal points and the staircase effect displayed the greatest fatigue resistance when normalized to yield strength. Furthermore oxygen analysis showed a large oxygen uptake during SLM processing which must be altered to meet ASTM medical grade standards and may significantly reduce fatigue life. These achieved fatigue properties indicate that NiTi scaffolds produced via SLM can provide sufficient mechanical support over an implants lifetime within stress range values experienced in real life. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Microcracks induce osteoblast alignment and maturation on hydroxyapatite scaffolds

Science.gov (United States)

Shu, Yutian

Physiological bone tissue is a mineral/collagen composite with a hierarchical structure. The features in bone, such as mineral crystals, fibers, and pores can range from the nanometer to the centimeter in size. Currently available bone tissue scaffolds primarily address the chemical composition, pore size, and pore size distribution. While these design parameters are extensively investigated for mimicking bone function and inducing bone regeneration, little is known about microcracks, which is a prevalent feature found in fractured bone in vivo and associated with fracture healing and repair. Since the purpose of bone tissue engineering scaffold is to enhance bone regeneration, the coincidence of microcracks and bone densification should not be neglected but rather be considered as a potential parameter in bone tissue engineering scaffold design. The purpose of this study is to test the hypothesis that microcracks enhance bone healing. In vitro studies were designed to investigate the osteoblast (bone forming cells) response to microcracks in dense (94%) hydroxyapatite substrates. Microcracks were introduced using a well-established Vickers indentation technique. The results of our study showed that microcracks induced osteoblast alignment, enhanced osteoblast attachment and more rapid maturation. These findings may provide insight into fracture healing mechanism(s) as well as improve the design of bone tissue engineering orthopedic scaffolds for more rapid bone regeneration.

Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects.

NARCIS (Netherlands)

Kretlow, J.D.; Spicer, P.P.; Jansen, J.A.; Vacanti, C.A.; Kasper, F.K.; Mikos, A.G.

2010-01-01

For bone tissue engineering, the benefits of incorporating mesenchymal stem cells (MSCs) into porous scaffolds are well established. There is, however, little consensus on the effects of or need for MSC handling ex vivo. Culture and expansion of MSCs adds length and cost, and likely increases risk

Overlapping bio-absorbable scaffolds: Aim for D2D technique?

Science.gov (United States)

Khan, Asaad A; Dangas, George D

2018-06-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-15

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

Advanced tissue engineering scaffold design for regeneration of the complex hierarchical periodontal structure.

Science.gov (United States)

Costa, Pedro F; Vaquette, Cédryck; Zhang, Qiyi; Reis, Rui L; Ivanovski, Saso; Hutmacher, Dietmar W

2014-03-01

This study investigated the ability of an osteoconductive biphasic scaffold to simultaneously regenerate alveolar bone, periodontal ligament and cementum. A biphasic scaffold was built by attaching a fused deposition modelled bone compartment to a melt electrospun periodontal compartment. The bone compartment was coated with a calcium phosphate (CaP) layer for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro for 6 weeks. The resulting constructs were then complemented with the placement of PDL cell sheets on the periodontal compartment, attached to a dentin block and subcutaneously implanted into athymic rats for 8 weeks. Scanning electron microscopy, X-ray diffraction, alkaline phosphatase and DNA content quantification, confocal laser microscopy, micro computerized tomography and histological analysis were employed to evaluate the scaffold's performance. The in vitro study showed that alkaline phosphatase activity was significantly increased in the CaP-coated samples and they also displayed enhanced mineralization. In the in vivo study, significantly more bone formation was observed in the coated scaffolds. Histological analysis revealed that the large pore size of the periodontal compartment permitted vascularization of the cell sheets, and periodontal attachment was achieved at the dentin interface. This work demonstrates that the combination of cell sheet technology together with an osteoconductive biphasic scaffold could be utilized to address the limitations of current periodontal regeneration techniques. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cornell Alliance for Science Evaluation of Consensus on Genetically Modified Food Safety: Weaknesses in Study Design.

Science.gov (United States)

Antoniou, Michael N; Robinson, Claire J

2017-01-01

Cornell Alliance for Science has launched an initiative in which "citizen scientists" are called upon to evaluate studies on health risks of genetically modified (GM) crops and foods. The purpose is to establish whether the consensus on GM food safety claimed by the American Association for the Advancement of Science (AAAS) is supported by a review of the scientific literature. The Alliance's citizen scientists are examining more than 12,000 publication abstracts to quantify how far the scientific literature supports the AAAS's statement. We identify a number of fundamental weaknesses in the Alliance's study design, including evaluation is based only on information provided in the publication abstract; there is a lack of clarity as to what material is included in the 12,000 study abstracts to be reviewed, since the number of appropriately designed investigations addressing GM food safety are few; there is uncertainty as to whether studies of toxic effects arising from GM crop-associated pesticides will be included; there is a lack of clarity regarding whether divergent yet equally valid interpretations of the same study will be taken into account; and there is no definition of the cutoff point for consensus or non-consensus on GM food safety. In addition, vital industry proprietary biosafety data on GM crops and associated pesticides are not publicly available and is thus cannot inform this project. Based on these weaknesses in the study design, we believe it is questionable as to whether any objective or meaningful conclusion can be drawn from the Alliance's initiative.

Rapid-prototyped PLGA/β-TCP/hydroxyapatite nanocomposite scaffolds in a rabbit femoral defect model

International Nuclear Information System (INIS)

Kim, Jinku; McBride, Sean; Alvarez-Urena, Pedro; Song, Young-Hye; Hollinger, Jeffrey O; Tellis, Brandi; Dean, David D; Sylvia, Victor L; Elgendy, Hoda; Ong, Joo

2012-01-01

Bone tissue engineering scaffolds composed of poly(d,l-lactide:glycolide) (DL-PLGA) and β-tricalcium phosphate (β-TCP) nanocomposites were prepared and characterized. Scaffolds with two specific architectures were produced via fused deposition modeling (FDM), a type of extrusion freeform fabrication. Microfilaments deposited at angles of 0° and 90° were designated as the ‘simple’ scaffold architecture, while those deposited at angles alternating between 0°, 90°, 45° and −45° were designated as the ‘complex’ scaffold architecture. In addition, the simple and complex scaffolds were coated with hydroxyapatite (HA). The surface morphology of the scaffolds was assessed before and after HA coating and uniform distribution of HA coating on the surface was observed by scanning electron microscopy. The scaffolds were implanted into rabbit femoral unicortical bone defects according to four treatment groups based on pore structure and HA coating. After 6 and 12 weeks, scaffolds and host bone were recovered and processed for histology. Data suggest that all configurations of the scaffolds integrated with the host bone and were biocompatible and thus may offer an exciting new scaffold platform for delivery of biologicals for bone regeneration. (paper)

Selective laser sintered poly-ε-caprolactone scaffold hybridized with collagen hydrogel for cartilage tissue engineering

International Nuclear Information System (INIS)

Chen, Chih-Hao; Chen, Jyh-Ping; Shyu, Victor Bong-Hang; Lee, Ming-Yih

2014-01-01

Selective laser sintering (SLS), an additive manufacturing (AM) technology, can be used to produce tissue engineering scaffolds with pre-designed macro and micro features based on computer-aided design models. An in-house SLS machine was built and 3D poly-ε-caprolactone (PCL) scaffolds were manufactured using a layer-by-layer design of scaffold struts with varying orientations (0°/45°/0°/45°, 0°/90°/0°/90°, 0°/45°/90°/135°), producing scaffolds with pores of different shapes and distribution. To better enhance the scaffold properties, chondrocytes were seeded in collagen gel and loaded in scaffolds for cartilage tissue engineering. Gel uptake and dynamic mechanical analysis demonstrated the better suitability of the 0°/90°/0°/90° scaffolds for reconstructive cartilage tissue engineering purposes. Chondrocytes were then seeded onto the 0°/90°/0°/90° scaffolds in collagen I hydrogel (PCL/COL1) and compared to medium-suspended cells in terms of their cartilage-like tissue engineering parameters. PCL/COL1 allowed better cell proliferation when compared to PCL or two-dimensional tissue culture polystyrene. Scanning electron microscopy and confocal microscopy observations demonstrated a similar trend for extracellular matrix production and cell survival. Glycosaminoglycan and collagen II quantification also demonstrated the superior matrix secretion properties of PCL/COL1 hybrid scaffolds. Collagen-gel-suspended chondrocytes loaded in SLS-manufactured PCL scaffolds may provide a means of producing tissue-engineered cartilage with customized shapes and designs via AM technology. (paper)

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.

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.

Microscale versus nanoscale scaffold architecture for mesenchymal stem cell chondrogenesis.

Science.gov (United States)

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

2011-03-01

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

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.

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.

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.

Design of 3D scaffolds for tissue engineering testing a tough polylactide-based graft copolymer

International Nuclear Information System (INIS)

Dorati, R.; Colonna, C.; Tomasi, C.; Genta, I.; Bruni, G.; Conti, B.

2014-01-01

The aim of this research was to investigate a tough polymer to develop 3D scaffolds and 2D films for tissue engineering applications, in particular to repair urethral strictures or defects. The polymer tested was a graft copolymer of polylactic acid (PLA) synthesized with the rationale to improve the toughness of the related PLA homopolymer. The LMP-3055 graft copolymer (in bulk) demonstrated to have negligible cytotoxicity (bioavailability > 85%, MTT test). Moreover, the LMP-3055 sterilized through gamma rays resulted to be cytocompatible and non-toxic, and it has a positive effect on cell biofunctionality, promoting the cell growth. 3D scaffolds and 2D film were prepared using different LMP-3055 polymer concentrations (7.5, 10, 12.5 and 15%, w/v), and the effect of polymer concentration on pore size, porosity and interconnectivity of the 3D scaffolds and 2D film was investigated. 3D scaffolds got better results for fulfilling structural and biofunctional requirements: porosity, pore size and interconnectivity, cell attachment and proliferation. 3D scaffolds obtained with 10 and 12.5% polymer solutions (3D-2 and 3D-3, respectively) were identified as the most suitable construct for the cell attachment and proliferation presenting pore size ranged between 100 and 400 μm, high porosity (77–78%) and well interconnected pores. In vitro cell studies demonstrated that all the selected scaffolds were able to support the cell proliferation, the cell attachment and growth resulting to their dependency on the polymer concentration and structural features. The degradation test revealed that the degradation of polymer matrix (ΔMw) and water uptake of 3D scaffolds exceed those of 2D film and raw polymer (used as control reference), while the mass loss of samples (3D scaffold and 2D film) resulted to be controlled, they showed good stability and capacity to maintain the physical integrity during the incubation time. - Highlights: • Tough PLA graft copolymer was proposed

Design of 3D scaffolds for tissue engineering testing a tough polylactide-based graft copolymer

Energy Technology Data Exchange (ETDEWEB)

Dorati, R., E-mail: rossella.dorati@unipv.it [Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia (Italy); Center for Tissue Engineering (CIT), University of Pavia, Via Ferrata 1, 27100 Pavia (Italy); Colonna, C. [Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia (Italy); Center for Tissue Engineering (CIT), University of Pavia, Via Ferrata 1, 27100 Pavia (Italy); Tomasi, C. [C.S.G.I., Department of Chemistry, Division of Physical Chemistry, University of Pavia, V.le Taramelli 16 I, 27100 Pavia (Italy); Genta, I. [Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia (Italy); Center for Tissue Engineering (CIT), University of Pavia, Via Ferrata 1, 27100 Pavia (Italy); Bruni, G. [C.S.G.I., Department of Chemistry, Division of Physical Chemistry, University of Pavia, V.le Taramelli 16 I, 27100 Pavia (Italy); Conti, B. [Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia (Italy); Center for Tissue Engineering (CIT), University of Pavia, Via Ferrata 1, 27100 Pavia (Italy)

2014-01-01

The aim of this research was to investigate a tough polymer to develop 3D scaffolds and 2D films for tissue engineering applications, in particular to repair urethral strictures or defects. The polymer tested was a graft copolymer of polylactic acid (PLA) synthesized with the rationale to improve the toughness of the related PLA homopolymer. The LMP-3055 graft copolymer (in bulk) demonstrated to have negligible cytotoxicity (bioavailability > 85%, MTT test). Moreover, the LMP-3055 sterilized through gamma rays resulted to be cytocompatible and non-toxic, and it has a positive effect on cell biofunctionality, promoting the cell growth. 3D scaffolds and 2D film were prepared using different LMP-3055 polymer concentrations (7.5, 10, 12.5 and 15%, w/v), and the effect of polymer concentration on pore size, porosity and interconnectivity of the 3D scaffolds and 2D film was investigated. 3D scaffolds got better results for fulfilling structural and biofunctional requirements: porosity, pore size and interconnectivity, cell attachment and proliferation. 3D scaffolds obtained with 10 and 12.5% polymer solutions (3D-2 and 3D-3, respectively) were identified as the most suitable construct for the cell attachment and proliferation presenting pore size ranged between 100 and 400 μm, high porosity (77–78%) and well interconnected pores. In vitro cell studies demonstrated that all the selected scaffolds were able to support the cell proliferation, the cell attachment and growth resulting to their dependency on the polymer concentration and structural features. The degradation test revealed that the degradation of polymer matrix (ΔMw) and water uptake of 3D scaffolds exceed those of 2D film and raw polymer (used as control reference), while the mass loss of samples (3D scaffold and 2D film) resulted to be controlled, they showed good stability and capacity to maintain the physical integrity during the incubation time. - Highlights: • Tough PLA graft copolymer was proposed

Polymer-Ceramic Composite Scaffolds: The Effect of Hydroxyapatite and β-tri-Calcium Phosphate

OpenAIRE

Boyang Huang; Guilherme Caetano; Cian Vyas; Jonny James Blaker; Carl Diver; Paulo Bártolo

2018-01-01

The design of bioactive scaffolds with improved mechanical and biological properties is an important topic of research. This paper investigates the use of polymer-ceramic composite scaffolds for bone tissue engineering. Different ceramic materials (hydroxyapatite (HA) and β-tri-calcium phosphate (TCP)) were mixed with poly-ε-caprolactone (PCL). Scaffolds with different material compositions were produced using an extrusion-based additive manufacturing system. The produced scaffolds were physi...

Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted anti-inflammatory ligands.

Science.gov (United States)

Kaur, Gaganpreet; Kaur, Maninder; Silakari, Om

2014-01-01

The recent research area endeavors to discover ultimate multi-target ligands, an increasingly feasible and attractive alternative to existing mono-targeted drugs for treatment of complex, multi-factorial inflammation process which underlays plethora of debilitated health conditions. In order to improvise this option, exploration of relevant chemical core scaffold will be an utmost need. Privileged benzimidazole scaffold being historically versatile structural motif could offer a viable starting point in the search for novel multi-target ligands against multi-factorial inflammation process since, when appropriately substituted, it can selectively modulate diverse receptors, pathways and enzymes associated with the pathogenesis of inflammation. Despite this remarkable capability, the multi-target capacity of the benzimidazole scaffold remains largely unexploited. With this in focus, the present review article attempts to provide synopsis of published research to exemplify the valuable use of benzimidazole nucleus and focus on their suitability as starting scaffold to develop multi-targeted anti-inflammatory ligands.

Impact of stent strut design in metallic stents and biodegradable scaffolds.

Science.gov (United States)

Foin, Nicolas; Lee, Renick D; Torii, Ryo; Guitierrez-Chico, Juan Luis; Mattesini, Alessio; Nijjer, Sukhjinder; Sen, Sayan; Petraco, Ricardo; Davies, Justin E; Di Mario, Carlo; Joner, Michael; Virmani, Renu; Wong, Philip

2014-12-20

Advances in the understanding of healing mechanisms after stent implantation have led to the recognition of stent strut thickness as an essential factor affecting re-endothelialization and overall long term vessel healing response after Percutaneous Coronary Interventions (PCI). Emergence of Drug-eluting stents (DESs) with anti-proliferative coating has contributed to reducing the incidence of restenosis and Target Lesion Revascularization (TVR), while progress and innovations in stent materials have in the meantime facilitated the design of newer platforms with more conformability and thinner struts, producing lesser injury and improving integration into the vessel wall. Recent advances in biodegradable metal and polymer materials now also allow for the design of fully biodegradable platforms, which are aimed at scaffolding the vessel only temporarily to prevent recoil and constrictive remodeling of the vessel during the initial period required, and are then progressively resorbed thereby avoiding the drawback of leaving an unnecessary implant permanently in the vessel. The aim of this article is to review recent evolution in stent material and stent strut design while understanding their impact on PCI outcomes. The article describes the different metallic alloys and biodegradable material properties and how these have impacted the evolution of stent strut thickness and ultimately outcomes in patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Design of 3D scaffolds for tissue engineering testing a tough polylactide-based graft copolymer.

Science.gov (United States)

Dorati, R; Colonna, C; Tomasi, C; Genta, I; Bruni, G; Conti, B

2014-01-01

The aim of this research was to investigate a tough polymer to develop 3D scaffolds and 2D films for tissue engineering applications, in particular to repair urethral strictures or defects. The polymer tested was a graft copolymer of polylactic acid (PLA) synthesized with the rationale to improve the toughness of the related PLA homopolymer. The LMP-3055 graft copolymer (in bulk) demonstrated to have negligible cytotoxicity (bioavailability >85%, MTT test). Moreover, the LMP-3055 sterilized through gamma rays resulted to be cytocompatible and non-toxic, and it has a positive effect on cell biofunctionality, promoting the cell growth. 3D scaffolds and 2D film were prepared using different LMP-3055 polymer concentrations (7.5, 10, 12.5 and 15%, w/v), and the effect of polymer concentration on pore size, porosity and interconnectivity of the 3D scaffolds and 2D film was investigated. 3D scaffolds got better results for fulfilling structural and biofunctional requirements: porosity, pore size and interconnectivity, cell attachment and proliferation. 3D scaffolds obtained with 10 and 12.5% polymer solutions (3D-2 and 3D-3, respectively) were identified as the most suitable construct for the cell attachment and proliferation presenting pore size ranged between 100 and 400μm, high porosity (77-78%) and well interconnected pores. In vitro cell studies demonstrated that all the selected scaffolds were able to support the cell proliferation, the cell attachment and growth resulting to their dependency on the polymer concentration and structural features. The degradation test revealed that the degradation of polymer matrix (ΔMw) and water uptake of 3D scaffolds exceed those of 2D film and raw polymer (used as control reference), while the mass loss of samples (3D scaffold and 2D film) resulted to be controlled, they showed good stability and capacity to maintain the physical integrity during the incubation time. © 2013.

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

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

Science.gov (United States)

Lan, Sheeny K.

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

Osteochondral tissue engineering: scaffolds, stem cells and applications

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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

Consensus on consensus: a synthesis of consensus estimates on human-caused global warming

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Cook, John; Oreskes, Naomi; Doran, Peter T.; Anderegg, William R. L.; Verheggen, Bart; Maibach, Ed W.; Carlton, J. Stuart; Lewandowsky, Stephan; Skuce, Andrew G.; Green, Sarah A.; Nuccitelli, Dana; Jacobs, Peter; Richardson, Mark; Winkler, Bärbel; Painting, Rob; Rice, Ken

2016-04-01

The consensus that humans are causing recent global warming is shared by 90%-100% of publishing climate scientists according to six independent studies by co-authors of this paper. Those results are consistent with the 97% consensus reported by Cook et al (Environ. Res. Lett. 8 024024) based on 11 944 abstracts of research papers, of which 4014 took a position on the cause of recent global warming. A survey of authors of those papers (N = 2412 papers) also supported a 97% consensus. Tol (2016 Environ. Res. Lett. 11 048001) comes to a different conclusion using results from surveys of non-experts such as economic geologists and a self-selected group of those who reject the consensus. We demonstrate that this outcome is not unexpected because the level of consensus correlates with expertise in climate science. At one point, Tol also reduces the apparent consensus by assuming that abstracts that do not explicitly state the cause of global warming (‘no position’) represent non-endorsement, an approach that if applied elsewhere would reject consensus on well-established theories such as plate tectonics. We examine the available studies and conclude that the finding of 97% consensus in published climate research is robust and consistent with other surveys of climate scientists and peer-reviewed studies.

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.

Pre-Service Mathematics Teachers' Noticing Skills and Scaffolding Practices

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Kilic, Hulya

2018-01-01

A 14-week course program was designed to investigate pre-service teachers' noticing skills and scaffolding practices. Six pre-service teachers were matched with a pair of sixth grade students to observe and scaffold students' mathematical understanding while they were working on the given tasks. Data was collected through pre-service teachers' own…

Using the Community of Inquiry Framework to Scaffold Online Tutoring

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Feng, Xiaoying; Xie, Jingjing; Liu, Yue

2017-01-01

Tutoring involves providing learners with a suitable level of structure and guidance to support their learning. This study reports on an exploration of how to design such structure and guidance (i.e., learning scaffolds) in the Chinese online educational context, and in so doing, answer the following two questions: (a) What scaffolding strategies…

3D printing of porous hydroxyapatite scaffolds intended for use in bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Cox, Sophie C.; Thornby, John A.; Gibbons, Gregory J., E-mail: G.J.Gibbons@warwick.ac.uk; Williams, Mark A.; Mallick, Kajal K.

2015-02-01

A systematic characterisation of bone tissue scaffolds fabricated via 3D printing from hydroxyapatite (HA) and poly(vinyl)alcohol (PVOH) composite powders is presented. Flowability of HA:PVOH precursor materials was observed to affect mechanical stability, microstructure and porosity of 3D printed scaffolds. Anisotropic behaviour of constructs and part failure at the boundaries of interlayer bonds was highlighted by compressive strength testing. A trade-off between the ability to facilitate removal of PVOH thermal degradation products during sintering and the compressive strength of green parts was revealed. The ultimate compressive strength of 55% porous green scaffolds printed along the Y-axis and dried in a vacuum oven for 6 h was 0.88 ± 0.02 MPa. Critically, the pores of 3D printed constructs could be user designed, ensuring bulk interconnectivity, and the imperfect packing of powder particles created an inherent surface roughness and non-designed porosity within the scaffold. These features are considered promising since they are known to facilitate osteoconduction and osteointegration in-vivo. Characterisation techniques utilised in this study include two funnel flow tests, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), compressive strength testing and computed tomography (CT). - Highlights: • Flowability of HA and PVOH powders corresponded to scaffold printability. • Anisotropic behaviour of 3D printed scaffolds was highlighted by compressive tests. • Maximum compressive strength of 3D printed 55% porous scaffolds was 0.88 MPa. • Imperfect packing of precursors resulted in a rough surface and microporosity. • A CT method was designed and used to quantify designed and non-designed porosity.

3D printing of porous hydroxyapatite scaffolds intended for use in bone tissue engineering applications

International Nuclear Information System (INIS)

Cox, Sophie C.; Thornby, John A.; Gibbons, Gregory J.; Williams, Mark A.; Mallick, Kajal K.

2015-01-01

A systematic characterisation of bone tissue scaffolds fabricated via 3D printing from hydroxyapatite (HA) and poly(vinyl)alcohol (PVOH) composite powders is presented. Flowability of HA:PVOH precursor materials was observed to affect mechanical stability, microstructure and porosity of 3D printed scaffolds. Anisotropic behaviour of constructs and part failure at the boundaries of interlayer bonds was highlighted by compressive strength testing. A trade-off between the ability to facilitate removal of PVOH thermal degradation products during sintering and the compressive strength of green parts was revealed. The ultimate compressive strength of 55% porous green scaffolds printed along the Y-axis and dried in a vacuum oven for 6 h was 0.88 ± 0.02 MPa. Critically, the pores of 3D printed constructs could be user designed, ensuring bulk interconnectivity, and the imperfect packing of powder particles created an inherent surface roughness and non-designed porosity within the scaffold. These features are considered promising since they are known to facilitate osteoconduction and osteointegration in-vivo. Characterisation techniques utilised in this study include two funnel flow tests, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), compressive strength testing and computed tomography (CT). - Highlights: • Flowability of HA and PVOH powders corresponded to scaffold printability. • Anisotropic behaviour of 3D printed scaffolds was highlighted by compressive tests. • Maximum compressive strength of 3D printed 55% porous scaffolds was 0.88 MPa. • Imperfect packing of precursors resulted in a rough surface and microporosity. • A CT method was designed and used to quantify designed and non-designed porosity

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

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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

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 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 development of methods to predict the strength and stiffness of biomaterials used in tissue engineering is critical for load-bearing applications in which the essential functional requirements are primarily mechanical. We previously quantified changes in the effective stiffness (E) of needled nonwoven polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) scaffolds due to tissue formation and scaffold degradation under three-point bending. Toward predicting these changes, we present a structural model for E of a needled nonwoven scaffold in flexure. The model accounted for the number and orientation of fibers within a representative volume element of the scaffold demarcated by the needling process. The spring-like effective stiffness of the curved fibers was calculated using the sinusoidal fiber shapes. Structural and mechanical properties of PGA and PLLA fibers and PGA, PLLA, and 50:50 PGA/PLLA scaffolds were measured and compared with model predictions. To verify the general predictive capability, the predicted dependence of E on fiber diameter was compared with experimental measurements. Needled nonwoven scaffolds were found to exhibit distinct preferred (PD) and cross-preferred (XD) fiber directions, with an E ratio (PD/XD) of approximately 3:1. The good agreement between the predicted and experimental dependence of E on fiber diameter (R2 = 0.987) suggests that the structural model can be used to design scaffolds with E values more similar to native soft tissues. A comparison with previous results for cell-seeded scaffolds (Engelmayr, G. C., Jr., et al., 2005, Biomaterials, 26(2), pp. 175-187) suggests, for the first time, that the primary mechanical effect of collagen deposition is an increase in the number of fiber-fiber bond points yielding effectively stiffer scaffold fibers. This finding indicated that the effects of tissue deposition on needled nonwoven scaffold mechanics do not follow a rule-of-mixtures behavior. These important results underscore

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.

Microscale architecture in biomaterial scaffolds for spatial control of neural cell behavior

Science.gov (United States)

Meco, Edi; Lampe, Kyle J.

2018-02-01

Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and 3D bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

Polymer-Ceramic Composite Scaffolds: The Effect of Hydroxyapatite and β-tri-Calcium Phosphate.

Science.gov (United States)

Huang, Boyang; Caetano, Guilherme; Vyas, Cian; Blaker, Jonny James; Diver, Carl; Bártolo, Paulo

2018-01-14

The design of bioactive scaffolds with improved mechanical and biological properties is an important topic of research. This paper investigates the use of polymer-ceramic composite scaffolds for bone tissue engineering. Different ceramic materials (hydroxyapatite (HA) and β-tri-calcium phosphate (TCP)) were mixed with poly-ε-caprolactone (PCL). Scaffolds with different material compositions were produced using an extrusion-based additive manufacturing system. The produced scaffolds were physically and chemically assessed, considering mechanical, wettability, scanning electron microscopy and thermal gravimetric tests. Cell viability, attachment and proliferation tests were performed using human adipose derived stem cells (hADSCs). Results show that scaffolds containing HA present better biological properties and TCP scaffolds present improved mechanical properties. It was also possible to observe that the addition of ceramic particles had no effect on the wettability of the scaffolds.

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.

Intraarticular Facet Injections for Low Back Pain: Design Considerations, Consensus Methodology to Develop the Protocol for a Randomized Controlled Trial.

Science.gov (United States)

Mars, Tom; Ellard, David R; Antrobus, James H L; Cairns, Melinda; Underwood, Martin; Haywood, Kirstie; Keohane, Susie; Sandhu, Harbinder; Griffiths, Frances

2015-01-01

Since the publication of guidelines by the UK National Institute for Health and Care Excellence (NICE) and the American Pain Society guidelines for low back pain in 2009 there have been deep divisions in the pain treatment community about the use of therapeutic intraarticular facet joint injections. While evidence for the effectiveness or not of intraarticular facet joint injections remains sparse, uncertainty will remain. The Warwick feasibility study, along with a concurrent study with a different design led by another group, aims to provide a stable platform from which the effectiveness and cost effectiveness of intraarticular facet joint injections added to normal care could be evaluated in randomized controlled trials (RCTs). To reach consensus on key design considerations for the Warwick facet feasibility study from which the study protocol and working manuals will be developed. A consensus conference involving expert professionals and lay members. Preliminary work identified 5 key design considerations for deliberation at our consensus conference. Three concerned patient assessment and treatment: diagnosis of possible facet joint pain, interaarticular facet joint injection technique, and best usual care. Two concerned trial analysis: a priori sub-groups and minimally important difference and are reported elsewhere. We did systematic evidence reviews of the design considerations and summarized the evidence. Our design questions and evidence summaries were distributed to all delegates. This formed the basis for discussions on the day. Clinical experts in all aspects of facet joint injection from across the UK along with lay people were invited via relevant organizations. Nominal group technique was used in 15 facilitated initial small group discussions. Further discussion and ranking was undertaken in plenary. All small group and plenary results were recorded and checked and verified post conference. Where necessary participants were contacted via email to

The fabrication and cell culture of three-dimensional rolled scaffolds with complex micro-architectures

International Nuclear Information System (INIS)

Liu Yaxiong; Li Xiao; Qu Xiaoli; Zhu Lin; He Jiankang; Zhao Qian; Wu Wanquan; Li Dichen

2012-01-01

Cell cultures for tissue engineering are traditionally prepared on two-dimensional or three-dimensional scaffolds with simple pores; however, this limits mass transportation, which is necessary for cell viability and function. In this paper, an innovative method is proposed for fabricating porous scaffolds with designed complex micro-architectures. Channels devised by computer-aided design were used to simulate features of blood vessels in native rat liver. Rapid prototyping and microreplication were used to produce a negative polydimethylsiloxane mold, and then a planar porous scaffold with predefined microchannel parameters was obtained by freeze-drying a silk fibroin/gelatin solution of an optimized concentration. After seeding with rat primary hepatocytes, the planar scaffold was rolled up to build spatial channels. By reconstructing the three-dimensional channel model in the scaffold in the form of micro-computed topography data and observing the cross-sections of the scroll, we confirmed that the bent channels were still interconnected, with restricted deviations. A comparison of the primary hepatocyte culture in the scaffolds with and without the devised channels proved that our design influenced cell organization and improved cell survival and proliferation. This method can be used for the construction of complex tissues for implantation and for culturing cells in vitro for biological tests and observations.

The Effect of Various Media Scaffolding on Increasing Understanding of Students' Geometry Concepts

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Sutiarso, Sugeng; Coesamin, M.; Nurhanurawati

2018-01-01

This study is a quasi-experimental research with pretest-posttest control group design, which aims to determine (1) the tendency of students in using various media scaffolding based on gender, and (2) effect of media scaffolding on increasing understanding of students' geometry concepts. Media scaffolding used this study is chart, props, and…

The promotion of angiogenesis induced by three-dimensional porous beta-tricalcium phosphate scaffold with different interconnection sizes via activation of PI3K/Akt pathways

Science.gov (United States)

Xiao, Xin; Wang, Wei; Liu, Dong; Zhang, Haoqiang; Gao, Peng; Geng, Lei; Yuan, Yulin; Lu, Jianxi; Wang, Zhen

2015-03-01

The porous architectural characteristics of biomaterials play an important role in scaffold revascularization. However, no consensus exists regarding optimal interconnection sizes for vascularization and its scaffold bioperformance with different interconnection sizes. Therefore, a series of disk-type beta-tricalcium phosphates with the same pore sizes and variable interconnections were produced to evaluate how the interconnection size influenced biomaterial vascularization in vitro and in vivo. We incubated human umbilical vein endothelial cells on scaffolds with interconnections of various sizes. Results showed that scaffolds with a 150 μm interconnection size ameliorated endothelial cell function evidenced by promoting cell adhesion and migration, increasing cell proliferation and enhancing expression of platelet-endothelial cell adhesion molecules and vascular endothelial growth factor. In vivo study was performed on rabbit implanted with scaffolds into the bone defect on femoral condyles. Implantation with scaffolds with 150 μm interconnection size significantly improved neovascularization as shown by micro-CT as compared to scaffolds with 100 and 120 μm interconnection sizes. Moreover, the aforementioned positive effects were abolished by blocking PI3K/Akt/eNOS pathway with LY-294002. Our study explicitly demonstrates that the scaffold with 150 μm interconnection size improves neovascularization via the PI3K/Akt pathway and provides a target for biomaterial inner structure modification to attain improved clinical performance in implant vascularization.

Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Shor, Lauren; Gueceri, Selcuk; Chang, Robert; Sun Wei [Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA (United States); Gordon, Jennifer; Kang Qian; Hartsock, Langdon; An Yuehuei [Department of Orthopedic Surgery, Medical University of South Carolina, Charleston, SC (United States)], E-mail: st963bya@drexel.edu, E-mail: guceri@drexel.edu, E-mail: rcc34@drexel.edu, E-mail: sunwei@drexel.edu, E-mail: kangqk@musc.edu, E-mail: hartsock@musc.edu, E-mail: any@musc.edu

2009-03-01

Bone tissue engineering is an emerging field providing viable substitutes for bone regeneration. Recent advances have allowed scientists and engineers to develop scaffolds for guided bone growth. However, success requires scaffolds to have specific macroscopic geometries and internal architectures conducive to biological and biophysical functions. Freeform fabrication provides an effective process tool to manufacture three-dimensional porous scaffolds with complex shapes and designed properties. A novel precision extruding deposition (PED) technique was developed to fabricate polycaprolactone (PCL) scaffolds. It was possible to manufacture scaffolds with a controlled pore size of 350 {mu}m with designed structural orientations using this method. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using scanning electron microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. An in vitro cell-scaffold interaction study was carried out using primary fetal bovine osteoblasts. Specifically, the cell proliferation and differentiation was evaluated by Alamar Blue assay for cell metabolic activity, alkaline phosphatase activity and osteoblast production of calcium. An in vivo study was performed on nude mice to determine the capability of osteoblast-seeded PCL to induce osteogenesis. Each scaffold was implanted subcutaneously in nude mice and, following sacrifice, was explanted at one of a series of time intervals. The explants were then evaluated histologically for possible areas of osseointegration. Microscopy and radiological examination showed multiple areas of osseous ingrowth suggesting that the osteoblast-seeded PCL scaffolds evoke osteogenesis in vivo. These studies demonstrated the viability of the PED process to fabricate PCL scaffolds having the necessary mechanical properties, structural integrity, and controlled pore size and interconnectivity desired for bone tissue engineering.

Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Shor, Lauren; Gueceri, Selcuk; Chang, Robert; Sun Wei; Gordon, Jennifer; Kang Qian; Hartsock, Langdon; An Yuehuei

2009-01-01

Bone tissue engineering is an emerging field providing viable substitutes for bone regeneration. Recent advances have allowed scientists and engineers to develop scaffolds for guided bone growth. However, success requires scaffolds to have specific macroscopic geometries and internal architectures conducive to biological and biophysical functions. Freeform fabrication provides an effective process tool to manufacture three-dimensional porous scaffolds with complex shapes and designed properties. A novel precision extruding deposition (PED) technique was developed to fabricate polycaprolactone (PCL) scaffolds. It was possible to manufacture scaffolds with a controlled pore size of 350 μm with designed structural orientations using this method. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using scanning electron microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. An in vitro cell-scaffold interaction study was carried out using primary fetal bovine osteoblasts. Specifically, the cell proliferation and differentiation was evaluated by Alamar Blue assay for cell metabolic activity, alkaline phosphatase activity and osteoblast production of calcium. An in vivo study was performed on nude mice to determine the capability of osteoblast-seeded PCL to induce osteogenesis. Each scaffold was implanted subcutaneously in nude mice and, following sacrifice, was explanted at one of a series of time intervals. The explants were then evaluated histologically for possible areas of osseointegration. Microscopy and radiological examination showed multiple areas of osseous ingrowth suggesting that the osteoblast-seeded PCL scaffolds evoke osteogenesis in vivo. These studies demonstrated the viability of the PED process to fabricate PCL scaffolds having the necessary mechanical properties, structural integrity, and controlled pore size and interconnectivity desired for bone tissue engineering

Fabricating a pearl/PLGA composite scaffold by the low-temperature deposition manufacturing technique for bone tissue engineering

International Nuclear Information System (INIS)

Xu Mingen; Li Yanlei; Suo Hairui; Wang Qiujun; Ge Yakun; Xu Ying; Yan Yongnian; Liu Li

2010-01-01

Here we developed a composite scaffold of pearl/poly(lactic-co-glycolic acid) (pearl/PLGA) utilizing the low-temperature deposition manufacturing (LDM). LDM makes it possible to fabricate scaffolds with designed microstructure and macrostructure, while keeping the bioactivity of biomaterials by working at a low temperature. Process optimization was carried out to fabricate a mixture of pearl powder, PLGA and 1,4-dioxane with the designed hierarchical structures, and freeze-dried at a temperature of -40 deg. C. Scaffolds with square and designated bone shape were fabricated by following the 3D model. Marrow stem cells (MSCs) were seeded on the pearl/PLGA scaffold and then cultured in a rotating cell culture system. The adhesion, proliferation and differentiation of MSCs into osteoblasts were determined using scanning electronic microscopy, WST-1 assay, alkaline phosphatase activity assay, immunofluorescence staining and real-time reverse transcription polymerase chain reaction. The results showed that the composite scaffold had high porosity (81.98 ± 3.75%), proper pore size (micropores: <10 μm; macropore: 495 ± 54 μm) and mechanical property (compressive strength: 0.81 ± 0.04 MPa; elastic modulus: 23.14 ± 0.75 MPa). The pearl/PLGA scaffolds exhibited better biocompatibility and osteoconductivity compared with the tricalcium phosphate/PLGA scaffold. All these results indicate that the pearl/PLGA scaffolds fulfill the basic requirements of bone tissue engineering scaffold.

Polymer-Ceramic Composite Scaffolds: The Effect of Hydroxyapatite and β-tri-Calcium Phosphate

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Boyang Huang

2018-01-01

Full Text Available The design of bioactive scaffolds with improved mechanical and biological properties is an important topic of research. This paper investigates the use of polymer-ceramic composite scaffolds for bone tissue engineering. Different ceramic materials (hydroxyapatite (HA and β-tri-calcium phosphate (TCP were mixed with poly-ε-caprolactone (PCL. Scaffolds with different material compositions were produced using an extrusion-based additive manufacturing system. The produced scaffolds were physically and chemically assessed, considering mechanical, wettability, scanning electron microscopy and thermal gravimetric tests. Cell viability, attachment and proliferation tests were performed using human adipose derived stem cells (hADSCs. Results show that scaffolds containing HA present better biological properties and TCP scaffolds present improved mechanical properties. It was also possible to observe that the addition of ceramic particles had no effect on the wettability of the scaffolds.

A primer of statistical methods for correlating parameters and properties of electrospun poly(l -lactide) scaffolds for tissue engineering-PART 1: Design of experiments

KAUST Repository

Seyedmahmoud, Rasoul

2014-03-20

Tissue engineering scaffolds produced by electrospinning are of enormous interest, but still lack a true understanding about the fundamental connection between the outstanding functional properties, the architecture, the mechanical properties, and the process parameters. Fragmentary results from several parametric studies only render some partial insights that are hard to compare and generally miss the role of parameters interactions. To bridge this gap, this article (Part-1 of 2) features a case study on poly-l-lactide scaffolds to demonstrate how statistical methods such as design of experiments can quantitatively identify the correlations existing between key scaffold properties and control parameters, in a systematic, consistent, and comprehensive manner disentangling main effects from interactions. The morphological properties (i.e., fiber distribution and porosity) and mechanical properties (Young\\'s modulus) are "charted" as a function of molecular weight (MW) and other electrospinning process parameters (the Xs), considering the single effect as well as interactions between Xs. For the first time, the major role of the MW emerges clearly in controlling all scaffold properties. The correlation between mechanical and morphological properties is also addressed.

Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering

Institute of Scientific and Technical Information of China (English)

Feng Fu; Chong Chen; Sai Zhang; Ming-liang Zhao; Xiao-hong Li; Zhe Qin; Chao Xu; Xu-yi Chen; Rui-xin Li; Li-na Wang; Ding-wei Peng; Hong-tao Sun; Yue Tu

2017-01-01

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer- aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine.

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

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Angélica de Antonio Jiménez

2008-06-01

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

Hidden realities inside PBL design processes: Is consensus design an impossible clash of interest between the individual and the collective, and is architecture its first victim?

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Ole Pihl

2015-06-01

following points: 1 How can a PBL group-based learning environment based on a dialogical consensus ensure that everyone is working towards the same goal? 2 Does consensus architecture secure a necessary analysis and interpretation of the context, or does it create a grey consensus architecture based on compromises? 3 Does the PBL-method evoke a certain expression in space, form and materiality, but perhaps exclude other (possibly better solutions? 4 Every group’s work depends on the interplay between the personalities of the individuals and the group. How does this interplay affect the creative process? This paper seeks answers to the initial question “Is consensus design an impossible clash of interest between the individual and the collective, and is architecture its first victim?” and suggests new possible methodological tools for the architectural design process that secure the level of quality in design education.

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)

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

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Edi Meco

2018-02-01

Full Text Available Biomaterial scaffolds mimic aspects of the native central nervous system (CNS extracellular matrix (ECM and have been extensively utilized to influence neural cell (NC behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and three-dimensional (3D bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

Porous alumina scaffold produced by sol-gel combined polymeric sponge method

Science.gov (United States)

Hasmaliza, M.; Fazliah, M. N.; Shafinaz, R. J.

2012-09-01

Sol gel is a novel method used to produce high purity alumina with nanometric scale. In this study, three-dimensional porous alumina scaffold was produced using sol-gel polymeric sponge method. Briefly, sol gel alumina was prepared by evaporation and polymeric sponge cut to designated sizes were immersed in the sol gel followed by sintering at 1250 and 1550°C. In order to study the cell interaction, the porous alumina scaffold was sterilized using autoclave prior to Human Mesenchymal Stem Cells (HMSCs) seeding on the scaffold and the cell proliferation was assessed by alamarBlue® assay. SEM results showed that during the 21 day period, HMSCs were able to attach on the scaffold surface and the interconnecting pores while maintaining its proliferation. These findings suggested the potential use of the porous alumina produced as a scaffold for implantation procedure.

A consensus linkage map of lentil based on DArT markers from three RIL mapping populations.

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Duygu Ates

Full Text Available Lentil (Lens culinaris ssp. culinaris Medikus is a diploid (2n = 2x = 14, self-pollinating grain legume with a haploid genome size of about 4 Gbp and is grown throughout the world with current annual production of 4.9 million tonnes.A consensus map of lentil (Lens culinaris ssp. culinaris Medikus was constructed using three different lentils recombinant inbred line (RIL populations, including "CDC Redberry" x "ILL7502" (LR8, "ILL8006" x "CDC Milestone" (LR11 and "PI320937" x "Eston" (LR39.The lentil consensus map was composed of 9,793 DArT markers, covered a total of 977.47 cM with an average distance of 0.10 cM between adjacent markers and constructed 7 linkage groups representing 7 chromosomes of the lentil genome. The consensus map had no gap larger than 12.67 cM and only 5 gaps were found to be between 12.67 cM and 6.0 cM (on LG3 and LG4. The localization of the SNP markers on the lentil consensus map were in general consistent with their localization on the three individual genetic linkage maps and the lentil consensus map has longer map length, higher marker density and shorter average distance between the adjacent markers compared to the component linkage maps.This high-density consensus map could provide insight into the lentil genome. The consensus map could also help to construct a physical map using a Bacterial Artificial Chromosome library and map based cloning studies. Sequence information of DArT may help localization of orientation scaffolds from Next Generation Sequencing data.

A consensus linkage map of lentil based on DArT markers from three RIL mapping populations.

Science.gov (United States)

Ates, Duygu; Aldemir, Secil; Alsaleh, Ahmad; Erdogmus, Semih; Nemli, Seda; Kahriman, Abdullah; Ozkan, Hakan; Vandenberg, Albert; Tanyolac, Bahattin

2018-01-01

Lentil (Lens culinaris ssp. culinaris Medikus) is a diploid (2n = 2x = 14), self-pollinating grain legume with a haploid genome size of about 4 Gbp and is grown throughout the world with current annual production of 4.9 million tonnes. A consensus map of lentil (Lens culinaris ssp. culinaris Medikus) was constructed using three different lentils recombinant inbred line (RIL) populations, including "CDC Redberry" x "ILL7502" (LR8), "ILL8006" x "CDC Milestone" (LR11) and "PI320937" x "Eston" (LR39). The lentil consensus map was composed of 9,793 DArT markers, covered a total of 977.47 cM with an average distance of 0.10 cM between adjacent markers and constructed 7 linkage groups representing 7 chromosomes of the lentil genome. The consensus map had no gap larger than 12.67 cM and only 5 gaps were found to be between 12.67 cM and 6.0 cM (on LG3 and LG4). The localization of the SNP markers on the lentil consensus map were in general consistent with their localization on the three individual genetic linkage maps and the lentil consensus map has longer map length, higher marker density and shorter average distance between the adjacent markers compared to the component linkage maps. This high-density consensus map could provide insight into the lentil genome. The consensus map could also help to construct a physical map using a Bacterial Artificial Chromosome library and map based cloning studies. Sequence information of DArT may help localization of orientation scaffolds from Next Generation Sequencing data.

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

our understanding of the cell-scaffold interaction in meniscus tissue engineering, which provides unique insight into the design of meniscus scaffolds for future clinical application. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hybrid Carbon-Based Scaffolds for Applications in Soft Tissue Reconstruction

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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

PENGARUH METODE SCAFFOLDING BERBASIS KONSTRUKTIVISME TERHADAP HASIL BELAJAR MATEMATIKA

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Indrawati Indrawati

2017-01-01

ABSTRACT This study is motivated by the fact that many students have difficulties in learning mathematics especially for junior highschool students. This study aims to know the implementation of scaffolding method based on constructivism to students’ mathematics achievement. This is an experimental study with one group pretest and posttest design. The sample were 32 students grade VIII. Data is analyzed by t-test and n-gain test. T-test result shows that sig=0,000<0,05, The average score increases 15,63 and based on N-gain test shows that students competence increases too. It means that scaffolding method based on constructivism influence students’ mathematics achievement significantly. Thus scaffolding method based on constructivism can be implemented in any instruction, because it can increase students’ achievement and students will get learning variation that can reduce boredom and motivate them to learn actively. Keywords: mathematics achievement; constructivism; scaffolding.

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

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Yan Chen

2012-01-01

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

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.

Accurate Fabrication of Hydroxyapatite Bone Models with Porous Scaffold Structures by Using Stereolithography

Energy Technology Data Exchange (ETDEWEB)

Maeda, Chiaki; Tasaki, Satoko; Kirihara, Soshu, E-mail: c-maeda@jwri.osaka-u.ac.jp [Joining and Welding Research Institute, Osaka University, 11-1 Mihogaoka, Ibaraki City, Osaka 567-0047 (Japan)

2011-05-15

Computer graphic models of bioscaffolds with four-coordinate lattice structures of solid rods in artificial bones were designed by using a computer aided design. The scaffold models composed of acryl resin with hydroxyapatite particles at 45vol. % were fabricated by using stereolithography of a computer aided manufacturing. After dewaxing and sintering heat treatment processes, the ceramics scaffold models with four-coordinate lattices and fine hydroxyapatite microstructures were obtained successfully. By using a computer aided analysis, it was found that bio-fluids could flow extensively inside the sintered scaffolds. This result shows that the lattice structures will realize appropriate bio-fluid circulations and promote regenerations of new bones.

Accurate Fabrication of Hydroxyapatite Bone Models with Porous Scaffold Structures by Using Stereolithography

International Nuclear Information System (INIS)

Maeda, Chiaki; Tasaki, Satoko; Kirihara, Soshu

2011-01-01

Computer graphic models of bioscaffolds with four-coordinate lattice structures of solid rods in artificial bones were designed by using a computer aided design. The scaffold models composed of acryl resin with hydroxyapatite particles at 45vol. % were fabricated by using stereolithography of a computer aided manufacturing. After dewaxing and sintering heat treatment processes, the ceramics scaffold models with four-coordinate lattices and fine hydroxyapatite microstructures were obtained successfully. By using a computer aided analysis, it was found that bio-fluids could flow extensively inside the sintered scaffolds. This result shows that the lattice structures will realize appropriate bio-fluid circulations and promote regenerations of new bones.

Tailored PVA/ECM Scaffolds for Cartilage Regeneration

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Elena Stocco

2014-01-01

Full Text Available Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to design in vitro a supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM, which is decellularized Wharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA. Wharton’s jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton’s jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration.

[Experts consensus of dental esthetic photography].

Science.gov (United States)

2017-05-09

Clinical photography in esthetic dentistry is an essential skill in clinical practice. It is widely applied clinically in multiple fields related to esthetic dentistry. Society of Esthetic Dentistry of Chinese Stomatological Association established a consensus for clinical photography and standards for images in esthetic dentistry in order to standardize domestic dental practitioners' procedure, and meet the demands of diagnosis and design in modern esthetic dentistry. It was also developed to facilitate domestic and international academic communication. Sixteen commonly used images in practice, which are of apparent importance in guiding esthetic analysis, design and implementation, are proposed in the standards. This consensus states the clinical significance of these images and the standard protocol of acquiring them.

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)

3D Tissue Scaffold Printing On Custom Artificial Bone Applications

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Betül ALDEMİR

2015-01-01

Full Text Available Production of defect-matching scaffolds is the most critical step in custom artificial bone applications. Three dimensional printing (3DP is one of the best techniques particularly for custom designs on artificial bone applications because of the high controllability and design independency. Our long-term aim is to implant an artificial custom bone that is cultured with patient's own mesenchymal stem cells after determining defect architecture on patient's bone by using CT-scan and printing that defect-matching 3D scaffold with appropriate nontoxic materials. In this study, preliminary results of strength and cytotoxicity measurements of 3D printed scaffolds with modified calcium sulfate compositepowder (MCSCP were presented. CAD designs were created and MCSCP were printed by a 3D printer (3DS, Visijet, PXL Core. Some samples were covered with salt solution in order to harden the samples. MCSCP and salt coated MCSCP were the two experimental groups in this study. Cytotoxicity and mechanical experiments were performed after surface examination withscanning electron microscope (SEM and light microscope. Tension tests were performed for MCSCP and salt coated MCSCP samples. The 3D scaffolds were sterilized with ethylene oxide gas sterilizer, ventilated and conditioned with DMEM (10% FBS. L929 mouse fibroblast cells were cultured on scaffolds (3 repetitive and cell viability was determined using MTT analysis. According to the mechanical results, the MCSCP group stands until average 71,305 N, while salt coated MCSCP group stands until 21,328N. Although the strength difference between two groups is statistically significant (p=0.001, Mann-Whitney U, elastic modulus is not (MCSCP=1,186Pa, salt coated MCSCP=1,169Pa, p=0.445. Cell viability (MTT analysis results on day 1, 3, and 5 demonstrated thatscaffolds hadno toxic effect to the L929 mouse fibroblast cells. Consequently, 3D printed samples with MCSCP could potentially be a strong alternative

Custom-Made Synthetic Scaffolds for Bone Reconstruction: A Retrospective, Multicenter Clinical Study on 15 Patients

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Fabrizia Luongo

2016-01-01

Full Text Available Purpose. To present a computer-assisted-design/computer-assisted-manufacturing (CAD/CAM technique for the design, fabrication, and clinical application of custom-made synthetic scaffolds, for alveolar ridge augmentation. Methods. The CAD/CAM procedure consisted of (1 virtual planning/design of the custom-made scaffold; (2 milling of the scaffold into the exact size/shape from a preformed synthetic bone block; (3 reconstructive surgery. The main clinical/radiographic outcomes were vertical/horizontal bone gain, any biological complication, and implant survival. Results. Fifteen patients were selected who had been treated with a custom-made synthetic scaffold for ridge augmentation. The scaffolds closely matched the shape of the defects: this reduced the operation time and contributed to good healing. A few patients experienced biological complications, such as pain/swelling (2/15: 13.3% and exposure of the scaffold (3/15: 20.0%; one of these had infection and complete graft loss. In all other patients, 8 months after reconstruction, a well-integrated newly formed bone was clinically available, and the radiographic evaluation revealed a mean vertical and horizontal bone gain of 2.1±0.9 mm and 3.0±1.0 mm, respectively. Fourteen implants were placed and restored with single crowns. The implant survival rate was 100%. Conclusions. Although positive outcomes have been found with custom-made synthetic scaffolds in alveolar ridge augmentation, further studies are needed to validate this technique.

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.

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

Two major factors hampering the broad use of rapid prototyped biomaterials for tissue engineering applications are the requirement for custom-designed or expensive research-grade three-dimensional (3D) printers and the limited selection of suitable thermoplastic biomaterials exhibiting physical characteristics desired for facile surgical handling and biological properties encouraging tissue integration. Properly designed thermoplastic biodegradable amphiphilic polymers can exhibit hydration-dependent hydrophilicity changes and stiffening behavior, which may be exploited to facilitate the surgical delivery/self-fixation of the scaffold within a physiological tissue environment. Compared to conventional hydrophobic polyesters, they also present significant advantages in blending with hydrophilic osteoconductive minerals with improved interfacial adhesion for bone tissue engineering applications. Here, we demonstrated the excellent blending of biodegradable, amphiphilic poly(D,L-lactic acid)-poly(ethylene glycol)-poly(D,L-lactic acid) (PLA-PEG-PLA) (PELA) triblock co-polymer with hydroxyapatite (HA) and the fabrication of high-quality rapid prototyped 3D macroporous composite scaffolds using an unmodified consumer-grade 3D printer. The rapid prototyped HA-PELA composite scaffolds and the PELA control (without HA) swelled (66% and 44% volume increases, respectively) and stiffened (1.38-fold and 4-fold increases in compressive modulus, respectively) in water. To test the hypothesis that the hydration-induced physical changes can translate into self-fixation properties of the scaffolds within a confined defect, a straightforward in vitro pull-out test was designed to quantify the peak force required to dislodge these scaffolds from a simulated cylindrical defect at dry versus wet states. Consistent with our hypothesis, the peak fixation force measured for the PELA and HA-PELA scaffolds increased 6-fold and 15-fold upon hydration, respectively. Furthermore, we showed that

A primer of statistical methods for correlating parameters and properties of electrospun poly(L-lactide) scaffolds for tissue engineering--PART 1: design of experiments.

Science.gov (United States)

Seyedmahmoud, Rasoul; Rainer, Alberto; Mozetic, Pamela; Maria Giannitelli, Sara; Trombetta, Marcella; Traversa, Enrico; Licoccia, Silvia; Rinaldi, Antonio

2015-01-01

Tissue engineering scaffolds produced by electrospinning are of enormous interest, but still lack a true understanding about the fundamental connection between the outstanding functional properties, the architecture, the mechanical properties, and the process parameters. Fragmentary results from several parametric studies only render some partial insights that are hard to compare and generally miss the role of parameters interactions. To bridge this gap, this article (Part-1 of 2) features a case study on poly-L-lactide scaffolds to demonstrate how statistical methods such as design of experiments can quantitatively identify the correlations existing between key scaffold properties and control parameters, in a systematic, consistent, and comprehensive manner disentangling main effects from interactions. The morphological properties (i.e., fiber distribution and porosity) and mechanical properties (Young's modulus) are "charted" as a function of molecular weight (MW) and other electrospinning process parameters (the Xs), considering the single effect as well as interactions between Xs. For the first time, the major role of the MW emerges clearly in controlling all scaffold properties. The correlation between mechanical and morphological properties is also addressed. © 2014 Wiley Periodicals, Inc.

Nanorod mediated collagen scaffolds as extra cellular matrix mimics

International Nuclear Information System (INIS)

Vedhanayagam, Mohan; Nair, Balachandran Unni; Sreeram, Kalarical Janardhanan; Mohan, Ranganathan

2015-01-01

Creating collagen scaffolds that mimic extracellular matrices without using toxic exogenous materials remains a big challenge. A new strategy to create scaffolds through end-to-end crosslinking through functionalized nanorods leading to well-designed architecture is presented here. Self-assembled scaffolds with a denaturation temperature of 110 °C, porosity of 70%, pore size of 0.32 μm and Young’s modulus of 231 MPa were developed largely driven by imine bonding between 3-mercapto-1-propanal (MPA) functionalized ZnO nanorods and collagen. The mechanical properties obtained were much higher than that of native collagen, collagen—MPA, collagen—3-mercapto-1-propanol (3MPOH) or collagen- 3-MPOH-ZnO, clearly bringing out the relevance of nanorod mediated assembly of fibrous networks. This new strategy has led to scaffolds with mechanical properties much higher than earlier reports and can provide support for cell growth and facilitation of cell attachment. (paper)

Improving Students' Speaking Ability through Scaffolding Technique

Directory of Open Access Journals (Sweden)

Gede Ginaya

2018-03-01

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

Influence of Additive Manufactured Scaffold Architecture on the Distribution of Surface Strains and Fluid Flow Shear Stresses and Expected Osteochondral Cell Differentiation.

Science.gov (United States)

Hendrikson, Wim J; Deegan, Anthony J; Yang, Ying; van Blitterswijk, Clemens A; Verdonschot, Nico; Moroni, Lorenzo; Rouwkema, Jeroen

2017-01-01

Scaffolds for regenerative medicine applications should instruct cells with the appropriate signals, including biophysical stimuli such as stress and strain, to form the desired tissue. Apart from that, scaffolds, especially for load-bearing applications, should be capable of providing mechanical stability. Since both scaffold strength and stress-strain distributions throughout the scaffold depend on the scaffold's internal architecture, it is important to understand how changes in architecture influence these parameters. In this study, four scaffold designs with different architectures were produced using additive manufacturing. The designs varied in fiber orientation, while fiber diameter, spacing, and layer height remained constant. Based on micro-CT (μCT) scans, finite element models (FEMs) were derived for finite element analysis (FEA) and computational fluid dynamics (CFD). FEA of scaffold compression was validated using μCT scan data of compressed scaffolds. Results of the FEA and CFD showed a significant impact of scaffold architecture on fluid shear stress and mechanical strain distribution. The average fluid shear stress ranged from 3.6 mPa for a 0/90 architecture to 6.8 mPa for a 0/90 offset architecture, and the surface shear strain from 0.0096 for a 0/90 offset architecture to 0.0214 for a 0/90 architecture. This subsequently resulted in variations of the predicted cell differentiation stimulus values on the scaffold surface. Fluid shear stress was mainly influenced by pore shape and size, while mechanical strain distribution depended mainly on the presence or absence of supportive columns in the scaffold architecture. Together, these results corroborate that scaffold architecture can be exploited to design scaffolds with regions that guide specific tissue development under compression and perfusion. In conjunction with optimization of stimulation regimes during bioreactor cultures, scaffold architecture optimization can be used to improve

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.

Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture

KAUST Repository

Inal, Sahika

2017-05-03

This work reports the design of a live-cell monitoring platform based on a macroporous scaffold of a conducting polymer, poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate). The conducting polymer scaffolds support 3D cell cultures due to their biocompatibility and tissue-like elasticity, which can be manipulated by inclusion of biopolymers such as collagen. Integration of a media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability. This also allows for co-culture of multiple cell types inside the scaffold. The inclusion of cells within the porous architecture affects the impedance of the electrically conducting polymer network and, thus, is utilized as an in situ tool to monitor cell growth. Therefore, while being an integral part of the 3D tissue, the conducting polymer is an active component, enhancing the tissue function, and forming the basis for a bioelectronic device with integrated sensing capability.

Parallel fabrication of macroporous scaffolds.

Science.gov (United States)

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

2018-07-01

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

Applying consensus standards to cask development

International Nuclear Information System (INIS)

Leatham, J.; Abbott, D.G.; Warrant, M.M.

1987-01-01

The Department of Energy's (DOE's) Office of Civilian Radioactive Waste Management is procuring cask systems for transporting commercial spent nuclear fuel and is encouraging development of innovative cask designs and materials to improve system efficiency. New designs and innovative materials require that consensus standards be established so that cask designers and regulators have criteria for determining acceptability. Recent DOE experience in certifying three spent fuel shipping casks, NUPAC-125B, TN-BRP, and TN-REG, is discussed. Certification of the NUPAC-125B was expedited because it was made of conventional American Society for Testing and Materials (ASTM) materials and complied with the American Society of Mechanical Engineers (ASME) Code and Nuclear Regulatory Commission Regulatory Guides. The TN-BRP and TN-REG cask designs are still being reviewed because baskets included in the casks are made of borated stainless steel, which has no ASTM Specification or ASME Code approval. The process of developing and approving consensus standards is discussed, including the role of ANSI and ANSI N14. Specific procedures for ASTM and ASME are described. A draft specification or standard must be prepared and then approved by the appropriate body. For new material applications to the ASME Code, an existing ASTM Specification is needed. These processes may require several years. The status of activities currently in progress to develop consensus standards for spent fuel casks is discussed, including (1) ASME NUPAC, and (2) ASTM Specifications for ductile cast iron and borated stainless steel

Consensus on Exercise Reporting Template (CERT)

DEFF Research Database (Denmark)

Slade, Susan C; Dionne, Clermont E; Underwood, Martin

2016-01-01

the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise......BACKGROUND: Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. OBJECTIVE: The aim of this study was to develop a standardized method for reporting exercise programs in clinical...... trials: the Consensus on Exercise Reporting Template (CERT). DESIGN AND METHODS: Using the EQUATOR Network's methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews...

Mechanoactive scaffold induces tendon remodeling and expression of fibrocartilage markers.

Science.gov (United States)

Spalazzi, Jeffrey P; Vyner, Moira C; Jacobs, Matthew T; Moffat, Kristen L; Lu, Helen H

2008-08-01

Biological fixation of soft tissue-based grafts for anterior cruciate ligament (ACL) reconstruction poses a major clinical challenge. The ACL integrates with subchondral bone through a fibrocartilage enthesis, which serves to minimize stress concentrations and enables load transfer between two distinct tissue types. Functional integration thus requires the reestablishment of this fibrocartilage interface on reconstructed ACL grafts. We designed and characterized a novel mechanoactive scaffold based on a composite of poly-alpha-hydroxyester nanofibers and sintered microspheres; we then used the scaffold to test the hypothesis that scaffold-induced compression of tendon grafts would result in matrix remodeling and the expression of fibrocartilage interface-related markers. Histology coupled with confocal microscopy and biochemical assays were used to evaluate the effects of scaffold-induced compression on tendon matrix collagen distribution, cellularity, proteoglycan content, and gene expression over a 2-week period. Scaffold contraction resulted in over 15% compression of the patellar tendon graft and upregulated the expression of fibrocartilage-related markers such as Type II collagen, aggrecan, and transforming growth factor-beta3 (TGF-beta3). Additionally, proteoglycan content was higher in the compressed tendon group after 1 day. The data suggest the potential of a mechanoactive scaffold to promote the formation of an anatomic fibrocartilage enthesis on tendon-based ACL reconstruction grafts.

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

Science.gov (United States)

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

2017-07-01

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

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

Science.gov (United States)

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

2017-02-01

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

Fabrication and evaluation of 3D β-TCP scaffold by novel direct-write assembly method

International Nuclear Information System (INIS)

Sa, Min Woo; Kim, Jong Young

2015-01-01

Various scaffold fabrication methods have been explored to enhance the cell interaction effects and mechanical properties of scaffolds in bone regeneration. Rapid prototyping (RP) for tissue engineering is a useful technology that may provide a potential scaffolding structure to regenerate, restore, and repair a damaged bone tissue or organ, that is, RP is a promising tissue engineering technique through a 3D scaffold fabrication by using a computer-aided design/computer-aided manufacturing system. In this study, 3D β-tricalcium phosphate (β-TCP) scaffolds were fabricated by a novel direct-write assembly method. The mechanical property of β-TCP scaffolds was analyzed by stress-strain curves by using a compression testing machine. Furthermore, an in vitro CCK-8 assay of osteosarcoma MG-63 cells showed the significant cell attachment and proliferation in the β-TCP scaffold.

Fabrication and evaluation of 3D β-TCP scaffold by novel direct-write assembly method

Energy Technology Data Exchange (ETDEWEB)

Sa, Min Woo; Kim, Jong Young [Andong National University, Andong (Korea, Republic of)

2015-11-15

Various scaffold fabrication methods have been explored to enhance the cell interaction effects and mechanical properties of scaffolds in bone regeneration. Rapid prototyping (RP) for tissue engineering is a useful technology that may provide a potential scaffolding structure to regenerate, restore, and repair a damaged bone tissue or organ, that is, RP is a promising tissue engineering technique through a 3D scaffold fabrication by using a computer-aided design/computer-aided manufacturing system. In this study, 3D β-tricalcium phosphate (β-TCP) scaffolds were fabricated by a novel direct-write assembly method. The mechanical property of β-TCP scaffolds was analyzed by stress-strain curves by using a compression testing machine. Furthermore, an in vitro CCK-8 assay of osteosarcoma MG-63 cells showed the significant cell attachment and proliferation in the β-TCP scaffold.

How important are scaffolds and their surface properties in regenerative medicine

Energy Technology Data Exchange (ETDEWEB)

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

2016-12-01

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

How important are scaffolds and their surface properties in regenerative medicine

International Nuclear Information System (INIS)

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

2016-01-01

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

Novel Vanadium-Loaded Ordered Collagen Scaffold Promotes Osteochondral Differentiation of Bone Marrow Progenitor Cells

Directory of Open Access Journals (Sweden)

Ana M. Cortizo

2016-01-01

Full Text Available Bone and cartilage regeneration can be improved by designing a functionalized biomaterial that includes bioactive drugs in a biocompatible and biodegradable scaffold. Based on our previous studies, we designed a vanadium-loaded collagen scaffold for osteochondral tissue engineering. Collagen-vanadium loaded scaffolds were characterized by SEM, FTIR, and permeability studies. Rat bone marrow progenitor cells were plated on collagen or vanadium-loaded membranes to evaluate differences in cell attachment, growth and osteogenic or chondrocytic differentiation. The potential cytotoxicity of the scaffolds was assessed by the MTT assay and by evaluation of morphological changes in cultured RAW 264.7 macrophages. Our results show that loading of VOAsc did not alter the grooved ordered structure of the collagen membrane although it increased membrane permeability, suggesting a more open structure. The VOAsc was released to the media, suggesting diffusion-controlled drug release. Vanadium-loaded membranes proved to be a better substratum than C0 for all evaluated aspects of BMPC biocompatibility (adhesion, growth, and osteoblastic and chondrocytic differentiation. In addition, there was no detectable effect of collagen or vanadium-loaded scaffolds on macrophage viability or cytotoxicity. Based on these findings, we have developed a new ordered collagen scaffold loaded with VOAsc that shows potential for osteochondral tissue engineering.

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

Science.gov (United States)

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

2015-01-01

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

A brief review of extrusion-based tissue scaffold bio-printing.

Science.gov (United States)

Ning, Liqun; Chen, Xiongbiao

2017-08-01

Extrusion-based bio-printing has great potential as a technique for manipulating biomaterials and living cells to create three-dimensional (3D) scaffolds for damaged tissue repair and function restoration. Over the last two decades, advances in both engineering techniques and life sciences have evolved extrusion-based bio-printing from a simple technique to one able to create diverse tissue scaffolds from a wide range of biomaterials and cell types. However, the complexities associated with synthesis of materials for bio-printing and manipulation of multiple materials and cells in bio-printing pose many challenges for scaffold fabrication. This paper presents an overview of extrusion-based bio-printing for scaffold fabrication, focusing on the prior-printing considerations (such as scaffold design and materials/cell synthesis), working principles, comparison to other techniques, and to-date achievements. This paper also briefly reviews the recent development of strategies with regard to hydrogel synthesis, multi-materials/cells manipulation, and process-induced cell damage in extrusion-based bio-printing. The key issue and challenges for extrusion-based bio-printing are also identified and discussed along with recommendations for future, aimed at developing novel biomaterials and bio-printing systems, creating patterned vascular networks within scaffolds, and preserving the cell viability and functions in scaffold bio-printing. The address of these challenges will significantly enhance the capability of extrusion-based bio-printing. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Indirect three-dimensional printing of synthetic polymer scaffold based on thermal molding process

International Nuclear Information System (INIS)

Park, Jeong Hun; Jung, Jin Woo; Cho, Dong-Woo; Kang, Hyun-Wook

2014-01-01

One of the major issues in tissue engineering has been the development of three-dimensional (3D) scaffolds, which serve as a structural template for cell growth and extracellular matrix formation. In scaffold-based tissue engineering, 3D printing (3DP) technology has been successfully applied for the fabrication of complex 3D scaffolds by using both direct and indirect techniques. In principle, direct 3DP techniques rely on the straightforward utilization of the final scaffold materials during the actual scaffold fabrication process. In contrast, indirect 3DP techniques use a negative mold based on a scaffold design, to which the desired biomaterial is cast and then sacrificed to obtain the final scaffold. Such indirect 3DP techniques generally impose a solvent-based process for scaffold fabrication, resulting in a considerable increase in the fabrication time and poor mechanical properties. In addition, the internal architecture of the resulting scaffold is affected by the properties of the biomaterial solution. In this study, we propose an advanced indirect 3DP technique using projection-based micro-stereolithography and an injection molding system (IMS) in order to address these challenges. The scaffold was fabricated by a thermal molding process using IMS to overcome the limitation of the solvent-based molding process in indirect 3DP techniques. The results indicate that the thermal molding process using an IMS has achieved a substantial reduction in scaffold fabrication time and has also provided the scaffold with higher mechanical modulus and strength. In addition, cell adhesion and proliferation studies have indicated no significant difference in cell activity between the scaffolds prepared by solvent-based and thermal molding processes. (paper)

Consensus standard requirements and guidance

International Nuclear Information System (INIS)

Putman, V.L.

1995-01-01

This report presents information from the ANS Criticality Alarm System Workshop relating to the consensus standard requirements and guidance. Topics presented include: definition; nomenclature; requirements and recommendations; purpose of criticality alarms; design criteria; signal characteristics; reliability, dependability and durability; tests; and emergency preparedness and planning

Robust consensus algorithm for multi-agent systems with exogenous disturbances under convergence conditions

Science.gov (United States)

Jiang, Yulian; Liu, Jianchang; Tan, Shubin; Ming, Pingsong

2014-09-01

In this paper, a robust consensus algorithm is developed and sufficient conditions for convergence to consensus are proposed for a multi-agent system (MAS) with exogenous disturbances subject to partial information. By utilizing H∞ robust control, differential game theory and a design-based approach, the consensus problem of the MAS with exogenous bounded interference is resolved and the disturbances are restrained, simultaneously. Attention is focused on designing an H∞ robust controller (the robust consensus algorithm) based on minimisation of our proposed rational and individual cost functions according to goals of the MAS. Furthermore, sufficient conditions for convergence of the robust consensus algorithm are given. An example is employed to demonstrate that our results are effective and more capable to restrain exogenous disturbances than the existing literature.

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

Science.gov (United States)

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

Nanofibrous nonmulberry silk/PVA scaffold for osteoinduction and osseointegration.

Science.gov (United States)

Bhattacharjee, Promita; Kundu, Banani; Naskar, Deboki; Maiti, Tapas K; Bhattacharya, Debasis; Kundu, Subhas C

2015-05-01

Poly-vinyl alcohol and nonmulberry tasar silk fibroin of Antheraea mylitta are blended to fabricate nanofibrous scaffolds for bone regeneration. Nanofibrous matrices are prepared by electrospinning the equal volume ratio blends of silk fibroin (2 and 4 wt%) with poly-vinyl alcohol solution (10 wt%) and designated as 2SF/PVA and 4SF/PVA, respectively with average nanofiber diameters of 177 ± 13 nm (2SF/PVA) and 193 ± 17 nm (4SF/PVA). Fourier transform infrared spectroscopy confirms retention of the secondary structure of fibroin in blends indicating the structural stability of neo-matrix. Both thermal stability and contact angle of the blends decrease with increasing fibroin percentage. Conversely, fibroin imparts mechanical stability to the blends; greater tensile strength is observed with increasing fibroin concentration. Blended scaffolds are biodegradable and support well the neo-bone matrix synthesis by human osteoblast like cells. The findings indicate the potentiality of nanofibrous scaffolds of nonmulberry fibroin as bone scaffolding material. © 2014 Wiley Periodicals, Inc.

Antimicrobial Cu-bearing stainless steel scaffolds

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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

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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.

Symphony: A case study for exploring and describing design methods and guidelines for learner-centered design

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Quintana, Christopher

Learner-centered design is an evolving software design perspective addressing the needs of learners---a specific audience trying to work in and understand new work practices in which they have a novice or naive understanding. Learner-centered design involves designing software that incorporates work support features (or scaffolding features) informed by social constructivist learning theories. By adopting a constructivist "learning by doing" perspective, scaffolds should support learners so they can mindfully engage in previously inaccessible work activity, which in turn allows those learners to progressively gain a better understanding of the new work. While there is an intuitive notion of "learner-centered design", there is less specific design information for developing learner-centered software. As a result, learner-centered software results from "educated guesses" and ad-hoc design approaches rather than from systematic design methods. Thus there is a need for specific design guidance to facilitate the development of learner-centered tools that help learners see the tasks, terminology, tools, etc. in the new work context and engage in that work. The research in this dissertation provides a more specific base of learner-centered design descriptions, methods, and guidelines to analyze work practices and design and evaluate scaffolds. The research approach involves using the development of Symphony---a scaffolded integrated tool environment for high-school students learning the work of computational science inquiry---as a case study to develop the learner-centered design approach. Symphony incorporates a variety of science tools with process scaffolding to support students in performing complex air pollution investigations. Six ninth-grade students used Symphony to investigate air quality questions for several weeks in an environmental science class. The student testing helped assess the effectiveness of the software scaffolding and in turn, the learner

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

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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.

Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.

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Naahidi, Sheva; Jafari, Mousa; Logan, Megan; Wang, Yujie; Yuan, Yongfang; Bae, Hojae; Dixon, Brian; Chen, P

2017-09-01

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Relationship between micro-porosity, water permeability and mechanical behavior in scaffolds for cartilage engineering.

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Vikingsson, L; Claessens, B; Gómez-Tejedor, J A; Gallego Ferrer, G; Gómez Ribelles, J L

2015-08-01

In tissue engineering the design and optimization of biodegradable polymeric scaffolds with a 3D-structure is an important field. The porous scaffold provide the cells with an adequate biomechanical environment that allows mechanotransduction signals for cell differentiation and the scaffolds also protect the cells from initial compressive loading. The scaffold have interconnected macro-pores that host the cells and newly formed tissue, while the pore walls should be micro-porous to transport nutrients and waste products. Polycaprolactone (PCL) scaffolds with a double micro- and macro-pore architecture have been proposed for cartilage regeneration. This work explores the influence of the micro-porosity of the pore walls on water permeability and scaffold compliance. A Poly(Vinyl Alcohol) with tailored mechanical properties has been used to simulate the growing cartilage tissue inside the scaffold pores. Unconfined and confined compression tests were performed to characterize both the water permeability and the mechanical response of scaffolds with varying size of micro-porosity while volume fraction of the macro-pores remains constant. The stress relaxation tests show that the stress response of the scaffold/hydrogel construct is a synergic effect determined by the performance of the both components. This is interesting since it suggests that the in vivo outcome of the scaffold is not only dependent upon the material architecture but also the growing tissue inside the scaffold׳s pores. On the other hand, confined compression results show that compliance of the scaffold is mainly controlled by the micro-porosity of the scaffold and less by hydrogel density in the scaffold pores. These conclusions bring together valuable information for customizing the optimal scaffold and to predict the in vivo mechanical behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapid prototyping for tissue-engineered bone scaffold by 3D printing and biocompatibility study.

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He, Hui-Yu; Zhang, Jia-Yu; Mi, Xue; Hu, Yang; Gu, Xiao-Yu

2015-01-01

The prototyping of tissue-engineered bone scaffold (calcined goat spongy bone-biphasic ceramic composite/PVA gel) by 3D printing was performed, and the biocompatibility of the fabricated bone scaffold was studied. Pre-designed STL file was imported into the GXYZ303010-XYLE 3D printing system, and the tissue-engineered bone scaffold was fabricated by 3D printing using gel extrusion. Rabbit bone marrow stromal cells (BMSCs) were cultured in vitro and then inoculated to the sterilized bone scaffold obtained by 3D printing. The growth of rabbit BMSCs on the bone scaffold was observed under the scanning electron microscope (SEM). The effect of the tissue-engineered bone scaffold on the proliferation and differentiation of rabbit BMSCs using MTT assay. Universal testing machine was adopted to test the tensile strength of the bone scaffold. The leachate of the bone scaffold was prepared and injected into the New Zealand rabbits. Cytotoxicity test, acute toxicity test, pyrogenic test and intracutaneous stimulation test were performed to assess the biocompatibility of the bone scaffold. Bone scaffold manufactured by 3D printing had uniform pore size with the porosity of about 68.3%. The pores were well interconnected, and the bone scaffold showed excellent mechanical property. Rabbit BMSCs grew and proliferated on the surface of the bone scaffold after adherence. MTT assay indicated that the proliferation and differentiation of rabbit BMSCs on the bone scaffold did not differ significantly from that of the cells in the control. In vivo experiments proved that the bone scaffold fabricated by 3D printing had no acute toxicity, pyrogenic reaction or stimulation. Bone scaffold manufactured by 3D printing allows the rabbit BMSCs to adhere, grow and proliferate and exhibits excellent biomechanical property and high biocompatibility. 3D printing has a good application prospect in the prototyping of tissue-engineered bone scaffold.

Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

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Thangarajah, Tanujan; Pendegrass, Catherine J.; Shahbazi, Shirin; Lambert, Simon; Alexander, Susan; Blunn, Gordon W.

2015-01-01

Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon. PMID:26665095

Bone regeneration by means of a three-dimensional printed scaffold in a rat cranial defect.

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Kwon, Doo Yeon; Park, Ji Hoon; Jang, So Hee; Park, Joon Yeong; Jang, Ju Woong; Min, Byoung Hyun; Kim, Wan-Doo; Lee, Hai Bang; Lee, Junhee; Kim, Moon Suk

2018-02-01

Recently, computer-designed three-dimensional (3D) printing techniques have emerged as an active research area with almost unlimited possibilities. In this study, we used a computer-designed 3D scaffold to drive new bone formation in a bone defect. Poly-L-lactide (PLLA) and bioactive β-tricalcium phosphate (TCP) were simply mixed to prepare ink. PLLA + TCP showed good printability from the micronozzle and solidification within few seconds, indicating that it was indeed printable ink for layer-by-layer printing. In the images, TCP on the surface of (and/or inside) PLLA in the printed PLLA + TCP scaffold looked dispersed. MG-63 cells (human osteoblastoma) adhered to and proliferated well on the printed PLLA + TCP scaffold. To assess new bone formation in vivo, the printed PLLA + TCP scaffold was implanted into a full-thickness cranial bone defect in rats. The new bone formation was monitored by microcomputed tomography and histological analysis of the in vivo PLLA + TCP scaffold with or without MG-63 cells. The bone defect was gradually spontaneously replaced with new bone tissues when we used both bioactive TCP and MG-63 cells in the PLLA scaffold. Bone formation driven by the PLLA + TCP30 scaffold with MG-63 cells was significantly greater than that in other experimental groups. Furthermore, the PLLA + TCP scaffold gradually degraded and matched well the extent of the gradual new bone formation on microcomputed tomography. In conclusion, the printed PLLA + TCP scaffold effectively supports new bone formation in a cranial bone defect. Copyright © 2017 John Wiley & Sons, Ltd.

Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

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Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

2017-09-01

Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design and characterization of dexamethasone-loaded poly (glycerol sebacate)-poly caprolactone/gelatin scaffold by coaxial electro spinning for soft tissue engineering.

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Nadim, Afsaneh; Khorasani, Saied Nouri; Kharaziha, Mahshid; Davoodi, Seyyed Mohammadreza

2017-09-01

The aim of this research was to fabricate dexamethasone (Dex)-loaded poly (glycerol sebacate) (PGS)-poly (caprolactone) (PCL)/gelatin (Gt) (PGS-PCL/Gt-Dex) fibrous scaffolds in the form of core/shell structure which have potential application in soft tissues. In this regard, after synthesize and characterizations of PGS, PGS-PCL and gelatin fibrous scaffolds were separately developed in order to optimize the electrospinning parameters. In the next step, coaxial electrospun fibrous scaffold of PGS-PCL/Gt fibrous scaffold with PGS-PCL as core and Gt as shell was developed and its mechanical, physical and chemical properties were characterized. Moreover, degradability, hydrophilicity and biocompatibility of PGS-PCL/Gt fibrous scaffold were evaluated. In addition, Dex was encapsulated in PGS-PCL/Gt fibrous scaffold and drug release was assessed for tissue engineering application. Results demonstrated the formation of coaxial fibrous scaffold with average porosity of 79% and average fiber size of 294nm. Moreover, PGS-PCL/Gt fibrous scaffold revealed lower elastic modulus, ultimate tensile and ultimate elongation than those of PGS-PCL scaffold and more close to mechanical properties of natural tissue. Furthermore, lower contact angle of PGS-PCL/Gt than that of PGS-PCL demonstrated improved surface hydrophilicity of scaffold. DEX release was sustained over a period time of 30days from the scaffolds via three steps consisting of an initial burst release, secondary linear phase release pattern with slower rate over 20days followed by an apparent zero-order release phase. MTT observations demonstrated that there was no evidence of toxicity in the samples with and without Dex. Our findings indicated that core/shell PGS-PCL/Gt-Dex fibrous could be used as a carrier for the sustained release of drugs relevant for tissue engineering which makes it appropriate for soft tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparison of Tissue Engineering Scaffolds Incorporated with Manuka Honey of Varying UMF

Directory of Open Access Journals (Sweden)

Katherine R. Hixon

2017-01-01

Full Text Available Purpose. Manuka honey (MH is an antibacterial agent specific to the islands of New Zealand containing both hydrogen peroxide and a Unique Manuka Factor (UMF. Although the antibacterial properties of MH have been studied, the effect of varying UMF of MH incorporated into tissue engineered scaffolds have not. Therefore, this study was designed to compare silk fibroin cryogels and electrospun scaffolds incorporated with a 5% MH concentration of various UMF. Methods. Characteristics such as porosity, bacterial clearance and adhesion, and cytotoxicity were compared. Results. Pore diameters for all cryogels were between 51 and 60 µm, while electrospun scaffolds were 10 µm. Cryogels of varying UMF displayed clearance of approximately 0.16 cm for E. coli and S. aureus. In comparison, the electrospun scaffolds clearance ranged between 0.5 and 1 cm. A glucose release of 0.5 mg/mL was observed for the first 24 hours by all scaffolds, regardless of UMF. With respect to cytotoxicity, neither scaffold caused the cell number to drop below 20,000. Conclusions. Overall, when comparing the effects of the various UMF within the two scaffolds, no significant differences were observed. This suggests that the fabricated scaffolds in this study displayed similar bacterial effects regardless of the UMF value.

Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells.

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Moradi, Ali; Ataollahi, Forough; Sayar, Katayoun; Pramanik, Sumit; Chong, Pan-Pan; Khalil, Alizan Abdul; Kamarul, Tunku; Pingguan-Murphy, Belinda

2016-01-01

Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts. © 2015 Wiley Periodicals, Inc.

Additive Manufacturing of Patient-Customizable Scaffolds for Tubular Tissues Using the Melt-Drawing Method.

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Tan, Yu Jun; Tan, Xipeng; Yeong, Wai Yee; Tor, Shu Beng

2016-11-03

Polymeric fibrous scaffolds for guiding cell growth are designed to be potentially used for the tissue engineering (TE) of tubular organs including esophagi, blood vessels, tracheas, etc. Tubular scaffolds were fabricated via melt-drawing of highly elastic poly(l-lactide-co-ε-caprolactone) (PLC) fibers layer-by-layer on a cylindrical mandrel. The diameter and length of the scaffolds are customizable via 3D printing of the mandrel. Thickness of the scaffolds was varied by changing the number of layers of the melt-drawing process. The morphology and tensile properties of the PLC fibers were investigated. The fibers were highly aligned with a uniform diameter. Their diameters and tensile properties were tunable by varying the melt-drawing speeds. These tailorable topographies and tensile properties show that the additive-based scaffold fabrication technique is customizable at the micro- and macro-scale for different tubular tissues. The merits of these scaffolds in TE were further shown by the finding that myoblast and fibroblast cells seeded onto the scaffolds in vitro showed appropriate cell proliferation and distribution. Human mesenchymal stem cells (hMSCs) differentiated to smooth muscle lineage on the microfibrous scaffolds in the absence of soluble induction factors, showing cellular shape modulation and scaffold elasticity may encourage the myogenic differentiation of stem cells.

Student Use of Scaffolding Software: Relationships with Motivation and Conceptual Understanding

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Butler, Kyle A.; Lumpe, Andrew

2008-10-01

This study was designed to theoretically articulate and empirically assess the role of computer scaffolds. In this project, several examples of educational software were developed to scaffold the learning of students performing high level cognitive activities. The software used in this study, Artemis, focused on scaffolding the learning of students as they performed information seeking activities. As 5th grade students traveled through a project-based science unit on photosynthesis, researchers used a pre-post design to test for both student motivation and student conceptual understanding of photosynthesis. To measure both variables, a motivation survey and three methods of concept map analysis were used. The student use of the scaffolding features was determined using a database that tracked students' movement between scaffolding tools. The gain scores of each dependent variable was then correlated to the students' feature use (time and hits) embedded in the Artemis Interface. This provided the researchers with significant relationships between the scaffolding features represented in the software and student motivation and conceptual understanding of photosynthesis. There were a total of three significant correlations in comparing the scaffolding use by hits (clicked on) with the dependent variables and only one significant correlation when comparing the scaffold use in time. The first significant correlation ( r = .499, p students' task value. This correlation supports the assumption that there is a positive relationship between the student use of the saving/viewing features and the students' perception of how interesting, how important, and how useful the task is. The second significant correlation ( r = 0.553, p students' self-efficacy for learning and performance. This correlation supports the assumption that there is a positive relationship between the student use of the searching features and the students' perception of their ability to accomplish a task as

CAD-CAM-generated hydroxyapatite scaffold to replace the mandibular condyle in sheep: preliminary results.

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Ciocca, Leonardo; Donati, Davide; Fantini, Massimiliano; Landi, Elena; Piattelli, Adriano; Iezzi, Giovanna; Tampieri, Anna; Spadari, Alessandro; Romagnoli, Noemi; Scotti, Roberto

2013-08-01

In this study, rapid CAD-CAM prototyping of pure hydroxyapatite to replace temporomandibular joint condyles was tested in sheep. Three adult animals were implanted with CAD-CAM-designed porous hydroxyapatite scaffolds as condyle substitutes. The desired scaffold shape was achieved by subtractive automated milling machining (block reduction). Custom-made surgical guides were created by direct metal laser sintering and were used to export the virtual planning of the bone cut lines into the surgical environment. Using the same technique, fixation plates were created and applied to the scaffold pre-operatively to firmly secure the condyles to the bone and to assure primary stability of the hydroxyapatite scaffolds during masticatory function. Four months post-surgery, the sheep were sacrificed. The hydroxyapatite scaffolds were explanted, and histological specimens were prepared. Different histological tissues penetrating the scaffold macropores, the sequence of bone remodeling, new apposition of bone and/or cartilage as a consequence of the different functional anatomic role, and osseointegration at the interface between the scaffold and bone were documented. This animal model was found to be appropriate for testing CAD-CAM customization and the biomechanical properties of porous, pure hydroxyapatite scaffolds used as joint prostheses.

Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation.

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Damaraju, Sita M; Shen, Yueyang; Elele, Ezinwa; Khusid, Boris; Eshghinejad, Ahmad; Li, Jiangyu; Jaffe, Michael; Arinzeh, Treena Livingston

2017-12-01

The discovery of electric fields in biological tissues has led to efforts in developing technologies utilizing electrical stimulation for therapeutic applications. Native tissues, such as cartilage and bone, exhibit piezoelectric behavior, wherein electrical activity can be generated due to mechanical deformation. Yet, the use of piezoelectric materials have largely been unexplored as a potential strategy in tissue engineering, wherein a piezoelectric biomaterial acts as a scaffold to promote cell behavior and the formation of large tissues. Here we show, for the first time, that piezoelectric materials can be fabricated into flexible, three-dimensional fibrous scaffolds and can be used to stimulate human mesenchymal stem cell differentiation and corresponding extracellular matrix/tissue formation in physiological loading conditions. Piezoelectric scaffolds that exhibit low voltage output, or streaming potential, promoted chondrogenic differentiation and piezoelectric scaffolds with a high voltage output promoted osteogenic differentiation. Electromechanical stimulus promoted greater differentiation than mechanical loading alone. Results demonstrate the additive effect of electromechanical stimulus on stem cell differentiation, which is an important design consideration for tissue engineering scaffolds. Piezoelectric, smart materials are attractive as scaffolds for regenerative medicine strategies due to their inherent electrical properties without the need for external power sources for electrical stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magmaris preliminary recommendation upon commercial launch: a consensus from the expert panel on 14 April 2016.

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Fajadet, Jean; Haude, Michael; Joner, Michael; Koolen, Jacques; Lee, Michael; Tölg, Ralph; Waksman, Ron

2016-09-18

Bioresorbable scaffolds represent an exciting milestone in the development of coronary stent technology with the potential to substantially improve the management of patients with coronary artery disease. In an attempt to provide first recommendations for the technology, experienced experts involved in the first-in-man studies met in Zurich on the 14 April 2016 in order to reach consensus on a responsible market introduction. This document will be updated regularly as new information from clinical trials becomes available and should be understood as a review of current data, opportunities, expectations, advice, and recommendations for future investigations.

In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

Energy Technology Data Exchange (ETDEWEB)

Tavakol, Shima [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of); Ragerdi Kashani, Iraj [School of Medicine, Tehran University of Medical Sciences, Department of Anatomy (Iran, Islamic Republic of); Azami, Mahmood [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Tissue Engineering (Iran, Islamic Republic of); Khoshzaban, Ahad [Tehran University of Medical Sciences, Iranian Tissue Bank Research and Preparation Center (Iran, Islamic Republic of); Tavakol, Behnaz [Kashan University of Medical Sciences, Department of Medicine (Iran, Islamic Republic of); Kharrazi, Sharmin [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of); Ebrahimi, Somayeh [University of Tarbiat Moallem, Department of Biology, Faculty of Sciences (Iran, Islamic Republic of); Rezayat Sorkhabadi, Seyed Mahdi, E-mail: sh_tavakol@razi.tums.ac.ir [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of)

2012-12-15

Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8-16 nm Multiplication-Sign 50-80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

International Nuclear Information System (INIS)

Tavakol, Shima; Ragerdi Kashani, Iraj; Azami, Mahmood; Khoshzaban, Ahad; Tavakol, Behnaz; Kharrazi, Sharmin; Ebrahimi, Somayeh; Rezayat Sorkhabadi, Seyed Mahdi

2012-01-01

Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8–16 nm × 50–80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

Engineering of Corneal Tissue through an Aligned PVA/Collagen Composite Nanofibrous Electrospun Scaffold.

Science.gov (United States)

Wu, Zhengjie; Kong, Bin; Liu, Rui; Sun, Wei; Mi, Shengli

2018-02-24

Corneal diseases are the main reason of vision loss globally. Constructing a corneal equivalent which has a similar strength and transparency with the native cornea, seems to be a feasible way to solve the shortage of donated cornea. Electrospun collagen scaffolds are often fabricated and used as a tissue-engineered cornea, but the main drawback of poor mechanical properties make it unable to meet the requirement for surgery suture, which limits its clinical applications to a large extent. Aligned polyvinyl acetate (PVA)/collagen (PVA-COL) scaffolds were electrospun by mixing collagen and PVA to reinforce the mechanical strength of the collagen electrospun scaffold. Human keratocytes (HKs) and human corneal epithelial cells (HCECs) inoculated on aligned and random PVA-COL electrospun scaffolds adhered and proliferated well, and the aligned nanofibers induced orderly HK growth, indicating that the designed PVA-COL composite nanofibrous electrospun scaffold is suitable for application in tissue-engineered cornea.

An experimental model to mimic the mechanical behavior of a scaffold in a cartilage defect

OpenAIRE

VIKINGSSON, LINE KARINA ALVA

2015-01-01

[EN] Abstract The main purpose of this thesis is the design and characterization of an experimental articular cartilage model. The in vitro model is composed of a macro and micro- porous Polycaprolactone scaffold with a Poly(Vinyl Alcohol) filling. The scaffold/hydrogel construct has been subjected to repeating number of freezing and thawing cycles in order to crosslink the hydrogel inside the scaffold's pores. The Poly(Vinyl Alcohol) resembles the growing cartilaginous tissue inside the ...

Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration.

Science.gov (United States)

Son, Jun-Sik; Kim, Su-Gwan; Oh, Ji-Su; Appleford, Mark; Oh, Sunho; Ong, Joo L; Lee, Kyu-Bok

2011-12-15

This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical-like shells were composed of porous hydroxyapatite (HA) with a hollow interior using a polymeric template-coating technique; the inner trabecular-like core consisted of porous poly(D,L-lactic acid) (PLA) that was loaded with dexamethasone (DEX) and was directly produced using a particle leaching/gas forming technique to create the inner diameter of the HA scaffold. It was observed that the HA and PLA parts of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore structures, and the boundary between both parts was tightly connected without any gaps. It was found that the structure of the combination scaffold was analogous to that of natural bone based on micro-computed tomography analysis. Additionally, the dense, uniform apatite layer was formed on the surface of the HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully released from the PLA of the biphasic scaffold over a 1-month period. This release caused human embryonic palatal mesenchyme cells to proliferate, differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded that this functionally graded scaffold is similar to natural bone and represents a potential bone-substitute material. Copyright © 2011 Wiley Periodicals, Inc.

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...

Biomimetic Layer-by-Layer Self-Assembly of Nanofilms, Nanocoatings, and 3D Scaffolds for Tissue Engineering

Directory of Open Access Journals (Sweden)

Shichao Zhang

2018-06-01

Full Text Available Achieving surface design and control of biomaterial scaffolds with nanometer- or micrometer-scaled functional films is critical to mimic the unique features of native extracellular matrices, which has significant technological implications for tissue engineering including cell-seeded scaffolds, microbioreactors, cell assembly, tissue regeneration, etc. Compared with other techniques available for surface design, layer-by-layer (LbL self-assembly technology has attracted extensive attention because of its integrated features of simplicity, versatility, and nanoscale control. Here we present a brief overview of current state-of-the-art research related to the LbL self-assembly technique and its assembled biomaterials as scaffolds for tissue engineering. An overview of the LbL self-assembly technique, with a focus on issues associated with distinct routes and driving forces of self-assembly, is described briefly. Then, we highlight the controllable fabrication, properties, and applications of LbL self-assembly biomaterials in the forms of multilayer nanofilms, scaffold nanocoatings, and three-dimensional scaffolds to systematically demonstrate advances in LbL self-assembly in the field of tissue engineering. LbL self-assembly not only provides advances for molecular deposition but also opens avenues for the design and development of innovative biomaterials for tissue engineering.

Enhancing Student Learning through Scaffolded Client Projects

Science.gov (United States)

Tomlinson, Elizabeth

2017-01-01

This article reports on the current status of client projects (CPs) in business communication courses, provides a scaffolded model for implementing CP, and assesses student learning in CPs. Using a longitudinal mixed method research design, survey data and qualitative materials from six semesters are presented. The instructor survey indicated need…

Maternal scaffolding behavior: links with parenting style and maternal education.

Science.gov (United States)

Carr, Amanda; Pike, Alison

2012-03-01

The purpose of this study was to specify the relationship between positive and harsh parenting and maternal scaffolding behavior. A 2nd aim was to disentangle the effects of maternal education and parenting quality, and a 3rd aim was to test whether parenting quality mediated the association between maternal education and scaffolding practices. We examined associations between positive and harsh parenting practices and contingent and noncontingent tutoring strategies. Ninety-six mother-child dyads (49 boys, 47 girls) from working- and middle-class English families participated. Mothers reported on parenting quality at Time 1 when children were 5 years old and again approximately 5 years later at Time 2. Mother-child pairs were observed working together on a block design task at Time 2, and interactions were coded for contingent (contingent shifting) and noncontingent (fixed failure feedback) dimensions of maternal scaffolding behavior. Positive and harsh parenting accounted for variance in contingent behavior over and above maternal education, whereas only harsh parenting accounted for unique variance in noncontingent scaffolding practices. Our findings provide new evidence for a more differentiated model of the relation between general parenting quality and specific scaffolding behaviors. PsycINFO Database Record (c) 2012 APA, all rights reserved.

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.

Engineering large-scale agent-based systems with consensus

Science.gov (United States)

Bokma, A.; Slade, A.; Kerridge, S.; Johnson, K.

1994-01-01

The paper presents the consensus method for the development of large-scale agent-based systems. Systems can be developed as networks of knowledge based agents (KBA) which engage in a collaborative problem solving effort. The method provides a comprehensive and integrated approach to the development of this type of system. This includes a systematic analysis of user requirements as well as a structured approach to generating a system design which exhibits the desired functionality. There is a direct correspondence between system requirements and design components. The benefits of this approach are that requirements are traceable into design components and code thus facilitating verification. The use of the consensus method with two major test applications showed it to be successful and also provided valuable insight into problems typically associated with the development of large systems.

Development of a custom biological scaffold for investigating ultrasound-mediated intracellular delivery

Energy Technology Data Exchange (ETDEWEB)

Bui, Loan [Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76010 (United States); Aleid, Adham [Department of Biomedical Technology, King Saud University, Riyadh 12372 (Saudi Arabia); Alassaf, Ahmad [Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33146 (United States); Department of Medical Equipment Technology, Majmaah University, Majmaah City 11952 (Saudi Arabia); Wilson, Otto C.; Raub, Christopher B. [Department of Biomedical Engineering, Catholic University of America, Washington, DC 20064 (United States); Frenkel, Victor, E-mail: vfrenkel@som.umaryland.edu [Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

2017-01-01

In vitro investigations of ultrasound mediated, intracellular drug and gene delivery (i.e. sonoporation) are typically carried out in cells cultured in standard plastic well plates. This creates conditions that poorly resemble in vivo conditions, as well as generating unwanted ultrasound phenomena that may confound the interpretation of results. Here, we present our results in the development of a biological scaffold for sonoporation studies. The scaffolds were comprised of cellulose fibers coated with chitosan and gelatin. Scaffold formulation was optimized for adherence and proliferation of mouse fibroblasts in terms of the ratio and relative concentration of the two constituents. The scaffolds were also shown to significantly reduce ultrasound reflections compared to the plastic well plates. A custom treatment chamber was designed and built, and the occurrence of acoustic cavitation in the chamber during the ultrasound treatments was detected; a requirement for the process of sonoporation. Finally, experiments were carried out to optimize the ultrasound exposures to minimize cellular damage. Ultrasound exposure was then shown to enable the uptake of 100 nm fluorescently labeled polystyrene nanoparticles in suspension into the cells seeded on scaffolds, compared to incubation of cell-seeded scaffolds with nanoparticles alone. These preliminary results set the basis for further development of this platform. They also provide motivation for the development of similar platforms for the controlled investigation of other ultrasound mediated cell and tissue therapies. - Highlights: • A custom, biological scaffold was developed, comprised of chitosan and gelatin. • The scaffold formulation was optimized for adhesion and proliferation of fibroblasts. • Investigations showed the scaffolds to be less reflective to ultrasound than plastic well plates. • The scaffolds were found to be suitable for investigations of ultrasound mediated intracellular nanoparticle

Breast Cancer Stem Cell Culture and Enrichment Using Poly(ε-Caprolactone Scaffolds

Directory of Open Access Journals (Sweden)

Sònia Palomeras

2016-04-01

Full Text Available The cancer stem cell (CSC population displays self-renewal capabilities, resistance to conventional therapies, and a tendency to post-treatment recurrence. Increasing knowledge about CSCs’ phenotype and functions is needed to investigate new therapeutic strategies against the CSC population. Here, poly(ε-caprolactone (PCL, a biocompatible polymer free of toxic dye, has been used to fabricate scaffolds, solid structures suitable for 3D cancer cell culture. It has been reported that scaffold cell culture enhances the CSCs population. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. PCL design and fabrication parameters were first determined and then optimized considering several measurable variables of the resulting scaffolds. MCF7 breast carcinoma cell line was used to assess scaffolds adequacy for 3D cell culture. To evaluate CSC enrichment, the Mammosphere Forming Index (MFI was performed in 2D and 3D MCF7 cultures. Results showed that the 60° scaffolds were more suitable for 3D culture than the 45° and 90° ones. Moreover, 3D culture experiments, in adherent and non-adherent conditions, showed a significant increase in MFI compared to 2D cultures (control. Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and enrich the CSCs population.

Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering.

Science.gov (United States)

Zhang, Xing; Xu, Bin; Puperi, Daniel S; Yonezawa, Aline L; Wu, Yan; Tseng, Hubert; Cuchiara, Maude L; West, Jennifer L; Grande-Allen, K Jane

2015-03-01

The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering. Copyright © 2014 Acta Materialia Inc. Published by 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...

Microstructural designs of spark-plasma sintered silicon carbide ceramic scaffolds

Energy Technology Data Exchange (ETDEWEB)

Roman-Manso, B.; Pablos, A. de; Belmonte, M.; Osendi, M. I.; Miranzo, P.

2014-04-01

Concentrated ceramic inks based on (SiC) powders, with different amounts of Y{sub 2}O{sub 3} and Al{sub 2}O{sub 3} as sintering aids, are developed for the adequate production of SiC scaffolds, with different patterned morphologies, by the Robocasting technique. The densification of the as-produced 3D structures, previously heat treated in air at 600 degree centigrade for the organics burn-out, is achieved with a Spark Plasma Sintering (SPS) furnace. The effects of the amount of sintering additives (7 - 20 wt. %) and the size of the SiC powders (50 nm and 0.5 {mu}m) on the processing of the inks, microstructure, hardness and elastic modulus of the sintered scaffolds, are studied. The use of nano-sized (SiC) powders significantly restricts the attainable maximum solids volume fraction of the ink (0.32 compared to 0.44 of the submicron-sized powders-based ink), involving a much larger porosity of the green ceramic bodies. Furthermore, reduced amounts of additives improve the mechanical properties of the ceramic skeleton; particularly, the stiffness. The grain size and specific surface area of the starting powders, the ink solids content, green porosity, amount of sintering additives and SPS temperatures are the main parameters to be taken into account for the production of these SiC cellular ceramics. (Author)

Anisotropic Shape-Memory Alginate Scaffolds Functionalized with Either Type I or Type II Collagen for Cartilage Tissue Engineering.

Science.gov (United States)

Almeida, Henrique V; Sathy, Binulal N; Dudurych, Ivan; Buckley, Conor T; O'Brien, Fergal J; Kelly, Daniel J

2017-01-01

Regenerating articular cartilage and fibrocartilaginous tissue such as the meniscus is still a challenge in orthopedic medicine. While a range of different scaffolds have been developed for joint repair, none have facilitated the development of a tissue that mimics the complexity of soft tissues such as articular cartilage. Furthermore, many of these scaffolds are not designed to function in mechanically challenging joint environments. The overall goal of this study was to develop a porous, biomimetic, shape-memory alginate scaffold for directing cartilage regeneration. To this end, a scaffold was designed with architectural cues to guide cellular and neo-tissue alignment, which was additionally functionalized with a range of extracellular matrix cues to direct stem cell differentiation toward the chondrogenic lineage. Shape-memory properties were introduced by covalent cross-linking alginate using carbodiimide chemistry, while the architecture of the scaffold was modified using a directional freezing technique. Introducing such an aligned pore structure was found to improve the mechanical properties of the scaffold, and promoted higher levels of sulfated glycosaminoglycans (sGAG) and collagen deposition compared to an isotropic (nonaligned) pore geometry when seeded with adult human stem cells. Functionalization with collagen improved stem cell recruitment into the scaffold and facilitated more homogenous cartilage tissue deposition throughout the construct. Incorporating type II collagen into the scaffolds led to greater cell proliferation, higher sGAG and collagen accumulation, and the development of a stiffer tissue compared to scaffolds functionalized with type I collagen. The results of this study demonstrate how both scaffold architecture and composition can be tailored in a shape-memory alginate scaffold to direct stem cell differentiation and support the development of complex cartilaginous tissues.

Evaluation of Nine Consensus Indices in Delphi Foresight Research and Their Dependency on Delphi Survey Characteristics: A Simulation Study and Debate on Delphi Design and Interpretation.

Science.gov (United States)

Birko, Stanislav; Dove, Edward S; Özdemir, Vural

2015-01-01

The extent of consensus (or the lack thereof) among experts in emerging fields of innovation can serve as antecedents of scientific, societal, investor and stakeholder synergy or conflict. Naturally, how we measure consensus is of great importance to science and technology strategic foresight. The Delphi methodology is a widely used anonymous survey technique to evaluate consensus among a panel of experts. Surprisingly, there is little guidance on how indices of consensus can be influenced by parameters of the Delphi survey itself. We simulated a classic three-round Delphi survey building on the concept of clustered consensus/dissensus. We evaluated three study characteristics that are pertinent for design of Delphi foresight research: (1) the number of survey questions, (2) the sample size, and (3) the extent to which experts conform to group opinion (the Group Conformity Index) in a Delphi study. Their impacts on the following nine Delphi consensus indices were then examined in 1000 simulations: Clustered Mode, Clustered Pairwise Agreement, Conger's Kappa, De Moivre index, Extremities Version of the Clustered Pairwise Agreement, Fleiss' Kappa, Mode, the Interquartile Range and Pairwise Agreement. The dependency of a consensus index on the Delphi survey characteristics was expressed from 0.000 (no dependency) to 1.000 (full dependency). The number of questions (range: 6 to 40) in a survey did not have a notable impact whereby the dependency values remained below 0.030. The variation in sample size (range: 6 to 50) displayed the top three impacts for the Interquartile Range, the Clustered Mode and the Mode (dependency = 0.396, 0.130, 0.116, respectively). The Group Conformity Index, a construct akin to measuring stubbornness/flexibility of experts' opinions, greatly impacted all nine Delphi consensus indices (dependency = 0.200 to 0.504), except the Extremity CPWA and the Interquartile Range that were impacted only beyond the first decimal point (dependency = 0

3D printing of novel osteochondral scaffolds with graded microstructure

Science.gov (United States)

Nowicki, Margaret A.; Castro, Nathan J.; Plesniak, Michael W.; Zhang, Lijie Grace

2016-10-01

Osteochondral tissue has a complex graded structure where biological, physiological, and mechanical properties vary significantly over the full thickness spanning from the subchondral bone region beneath the joint surface to the hyaline cartilage region at the joint surface. This presents a significant challenge for tissue-engineered structures addressing osteochondral defects. Fused deposition modeling (FDM) 3D bioprinters present a unique solution to this problem. The objective of this study is to use FDM-based 3D bioprinting and nanocrystalline hydroxyapatite for improved bone marrow human mesenchymal stem cell (hMSC) adhesion, growth, and osteochondral differentiation. FDM printing parameters can be tuned through computer aided design and computer numerical control software to manipulate scaffold geometries in ways that are beneficial to mechanical performance without hindering cellular behavior. Additionally, the ability to fine-tune 3D printed scaffolds increases further through our investment casting procedure which facilitates the inclusion of nanoparticles with biochemical factors to further elicit desired hMSC differentiation. For this study, FDM was used to print investment-casting molds innovatively designed with varied pore distribution over the full thickness of the scaffold. The mechanical and biological impacts of the varied pore distributions were compared and evaluated to determine the benefits of this physical manipulation. The results indicate that both mechanical properties and cell performance improve in the graded pore structures when compared to homogeneously distributed porous and non-porous structures. Differentiation results indicated successful osteogenic and chondrogenic manipulation in engineered scaffolds.

A consensus statement on how to conduct inclusive health research.

Science.gov (United States)

Frankena, T K; Naaldenberg, J; Cardol, M; Garcia Iriarte, E; Buchner, T; Brooker, K; Embregts, P; Joosa, E; Crowther, F; Fudge Schormans, A; Schippers, A; Walmsley, J; O'Brien, P; Linehan, C; Northway, R; van Schrojenstein Lantman-de Valk, H; Leusink, G

2018-04-11

The active involvement of people with intellectual disabilities in research, or inclusive research, is relatively common. However, inclusive health research is less common, even though it is expected to lead to appropriate healthcare and increased quality of life. Inclusive health research can build upon lessons learned from inclusive research. A total of 17 experts on inclusive (health) research without intellectual disabilities and 40 experts with intellectual disabilities collaborated in this consensus statement. The consensus statement was developed in three consecutive rounds: (1) an initial feedback round; (2) a roundtable discussion at the 2016 International Association for the Scientific Study of Intellectual and Developmental Disabilities World Congress; and (3) a final feedback round. This consensus statement provides researchers with guidelines, agreed upon by experts in the field, regarding attributes, potential outcomes, reporting and publishing, and future research directions, for designing and conducting inclusive health research. Consensus was reached on how to design and conduct inclusive health research. However, this statement should be continuously adapted to incorporate recent knowledge. The focus of this consensus statement is largely on inclusive health research, but the principles can also be applied to other areas. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Morphological Effects of HA on the Cell Compatibility of Electrospun HA/PLGA Composite Nanofiber Scaffolds

Directory of Open Access Journals (Sweden)

Adnan Haider

2014-01-01

Full Text Available Tissue engineering is faced with an uphill challenge to design a platform with appropriate topography and suitable surface chemistry, which could encourage desired cellular activities and guide bone tissue regeneration. To develop such scaffolds, composite nanofiber scaffolds of nHA and sHA with PLGA were fabricated using electrospinning technique. nHA was synthesized using precipitation method, whereas sHA was purchased. The nHA and sHA were suspended in PLGA solution separately and electrospun at optimized electrospinning parameters. The composite nanofiber scaffolds were characterized by FE-SEM, EDX analysis, TEM, XRD analysis, FTIR, and X-ray photoelectron. The potential of the HA/PLGA composite nanofiber as bone scaffolds in terms of their bioactivity and biocompatibility was assessed by culturing the osteoblastic cells onto the composite nanofiber scaffolds. The results from in vitro studies revealed that the nHA/PLGA composite nanofiber scaffolds showed higher cellular adhesion, proliferation, and enhanced osteogenesis performance, along with increased Ca+2 ions release compared to the sHA/PLGA composite nanofiber scaffolds and pristine PLGA nanofiber scaffold. The results show that the structural dependent property of HA might affect its potential as bone scaffold and implantable materials in regenerative medicine and clinical tissue engineering.

Design, fabrication and perivascular implantation of bioactive scaffolds engineered with human adventitial progenitor cells for stimulation of arteriogenesis in peripheral ischemia

International Nuclear Information System (INIS)

Carrabba, M; De Maria, C; Vozzi, G; Oikawa, A; Reni, C; Rodriguez-Arabaolaza, I; Spencer, H; Slater, S; Avolio, E; Dang, Z; Madeddu, P; Spinetti, G

2016-01-01

Cell therapy represents a promising option for revascularization of ischemic tissues. However, injection of dispersed cells is not optimal to ensure precise homing into the recipient’s vasculature. Implantation of cell-engineered scaffolds around the occluded artery may obviate these limitations. Here, we employed the synthetic polymer polycaprolactone for fabrication of 3D woodpile- or channel-shaped scaffolds by a computer-assisted writing system (pressure assisted micro-syringe square), followed by deposition of gelatin (GL) nanofibers by electro-spinning. Scaffolds were then cross-linked with natural (genipin, GP) or synthetic (3-glycidyloxy-propyl-trimethoxy-silane, GPTMS) agents to improve mechanical properties and durability in vivo. The composite scaffolds were next fixed by crown inserts in each well of a multi-well plate and seeded with adventitial progenitor cells (APCs, 3 cell lines in duplicate), which were isolated/expanded from human saphenous vein surgical leftovers. Cell density, alignment, proliferation and viability were assessed 1 week later. Data from in vitro assays showed channel-shaped/GPTMS-crosslinked scaffolds confer APCs with best alignment and survival/growth characteristics. Based on these results, channel-shaped/GPTMS-crosslinked scaffolds with or without APCs were implanted around the femoral artery of mice with unilateral limb ischemia. Perivascular implantation of scaffolds accelerated limb blood flow recovery, as assessed by laser Doppler or fluorescent microspheres, and increased arterial collaterals around the femoral artery and in limb muscles compared with non-implanted controls. Blood flow recovery and perivascular arteriogenesis were additionally incremented by APC-engineered scaffolds. In conclusion, perivascular application of human APC-engineered scaffolds may represent a novel option for targeted delivery of therapeutic cells in patients with critical limb ischemia. (paper)

Scaffolding knowledge building in a Web-based communication and cultural competence program for international medical graduates.

Science.gov (United States)

Lax, Leila R; Russell, M Lynn; Nelles, Laura J; Smith, Cathy M

2009-10-01

Professional behaviors, tacitly understood by Canadian-trained physicians, are difficult to teach and often create practice barriers for IMGs. The purpose of this design research study was to develop a Web-based program simulating Canadian medical literacy and culture, and to evaluate strategies of scaffolding individual knowledge building. Study 1 (N = 20) examined usability and pedagogic design. Studies 2 (N = 39) and 3 (N = 33) examined case participation patterns. Model design was validated in Study 1. Studies 2 and 3 demonstrated high levels of participation, on unprompted third tries, on knowledge tests. Recursive patterns were strongest on Reflective Exercises. Five strategies scaffolded knowledge building: (1) video simulations, (2) contextualized resources, (3) concurrent feedback, (4) Reflective Exercises, and (5) commentaries prompting "reflection on reflection." Scaffolded design supports complex knowledge building. These findings are concurrent with educational research on the importance of recursion and revision of knowledge for improvable and relational understanding.

Voting experiments: Bandwagon voting or false-consensus effect?

OpenAIRE

Ivo Bischoff; Henrik Egbert

2008-01-01

In an experiment designed to test for expressive voting, Tyran (JPubEc 2004) found a strong positive correlation between the participants' approval for a proposal to donate money for charity and their expected approval rate for fellow voters. This phenomenon can be due to bandwagon voting or a false consensus effect. The social science literature reports both effects for voting decisions. Replicating Tyran's experiment and adding new treatments, we provide evidence for a false consensus effec...

Deriving consensus rankings via multicriteria decision making methodology

OpenAIRE

Amy Poh Ai Ling; Mohamad Nasir Saludin; Masao Mukaidono

2012-01-01

Purpose - This paper seeks to take a cautionary stance to the impact of the marketing mix on customer satisfaction, via a case study deriving consensus rankings for benchmarking on selected retail stores in Malaysia. Design/methodology/approach - The ELECTRE I model is used in deriving consensus rankings via multicriteria decision making method for benchmarking base on the marketing mix model 4P's. Descriptive analysis is used to analyze best practice among the four marketing tactics. Finding...

Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.

Science.gov (United States)

Rustom, Laurence E; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W; Lu, Yan; Markel, Mark D; Picart, Catherine; Wagoner Johnson, Amy J

2016-10-15

The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF‾, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF‾, of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. The increasing demand for bone repair calls for more efficacious bone scaffolds and calcium phosphate-based materials are considered suitable for this application. Macropores (>100μm) are necessary for bone ingrowth and vascularization. However, studies have shown that microporosity (micropore-induced capillarity had the potential to enhance bone growth in vivo. This work illustrates the positive effects of capillarity on bone regeneration in vivo; it demonstrates that micropore-induced capillarity significantly

Developmental Scaffolding

DEFF Research Database (Denmark)

Giorgi, Franco; Bruni, Luis Emilio

2015-01-01

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

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

Science.gov (United States)

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

2013-10-01

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

Computational Exploration of Molecular Scaffolds in Medicinal Chemistry.

Science.gov (United States)

Hu, Ye; Stumpfe, Dagmar; Bajorath, Jürgen

2016-05-12

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

Development of biodegradable scaffolds based on magnetically guided assembly of magnetic sugar particles.

Science.gov (United States)

Hu, Chengzhi; Uchida, Tomoyuki; Tercero, Carlos; Ikeda, Seiichi; Ooe, Katsutoshi; Fukuda, Toshio; Arai, Fumihito; Negoro, Makoto; Kwon, Guiryong

2012-05-31

Biodegradable scaffolds with controlled pore layout and porosity have great significance in tissue engineering for cell penetration, tissue ingrowth, vascularization, and nutrient delivery. Porogen leaching has been commonly used to control pore size, pore structure and porosity in the scaffold. In this paper we focus on the use/development of two magnetically guided porogen assembly methods using magnetic sugar particles (MSPs) for scaffold fabrication. First, a patterning device is utilized to align MSPs following designed templates. Then a magnetic sheet film is fabricated by mixing poly(vinyl alcohol, PVA) and NdFeB powder for steering the MSPs. After poly(l-lactide-co-ɛ-caprolactone) (PLCL) casting and removal of the sugar template, a scaffold with spherical pores is obtained. The surface and the inner structure of the scaffolds are evaluated using light and electron micrographs showing their interconnection of pores, pore wall morphology and porosity. Single layer scaffolds with the size of 8mm in width and 10mm in length were constructed with controllable pore diameters in the ranges of 105-150 μm, 250-300 μm and 425-500 μm. Copyright © 2012 Elsevier B.V. All rights reserved.

A functionally gradient variational porosity architecture for hollowed scaffolds fabrication

Energy Technology Data Exchange (ETDEWEB)

Khoda, A K M [Department of Industrial Engineering, University at Buffalo, Buffalo, NY 14260 (United States); Ozbolat, Ibrahim T [Department of Mechanical and Industrial Engineering, Center for Computer Aided Design, University of Iowa, Iowa City, IA 52242-1527 (United States); Koc, Bahattin, E-mail: bahattinkoc@sabanciuniv.edu [Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul 34956 (Turkey)

2011-09-15

This paper presents a novel continuous tool-path planning methodology for hollowed scaffold fabrication in tissue engineering. A new functionally gradient porous architecture is proposed with a continuous material deposition planning scheme. A controllable variational pore size and hence the porosity have been achieved with a combination of two geometrically oriented consecutive layers. The desired porosity has been achieved with consecutive layers by geometrically partitioning each layer into sub-regions based on the area and the tissue scaffold design constraints. A continuous, interconnected and optimized tool-path for layers has been generated for a three-dimensional biomaterial deposition/printing process. A zigzag pattern tool-path has been proposed for an accumulated sub-region layer, and a concentric spiral-like optimal tool-path pattern has been generated for the successive layer to ensure continuity along the structure. Three-dimensional layers, formed by the proposed tool-path plan, vary the pore size and the porosity based on the biological and mechanical requirements. Several examples demonstrate the proposed methodology along with illustrative results. Also a comparative study between the proposed design and conventional Cartesian coordinate scaffolds has been performed. The results demonstrate a significant reduction in design error with the proposed method. Moreover, sample examples have been fabricated using a micro-nozzle biomaterial deposition system, and characterized for validation.

A functionally gradient variational porosity architecture for hollowed scaffolds fabrication

International Nuclear Information System (INIS)

Khoda, A K M; Ozbolat, Ibrahim T; Koc, Bahattin

2011-01-01

This paper presents a novel continuous tool-path planning methodology for hollowed scaffold fabrication in tissue engineering. A new functionally gradient porous architecture is proposed with a continuous material deposition planning scheme. A controllable variational pore size and hence the porosity have been achieved with a combination of two geometrically oriented consecutive layers. The desired porosity has been achieved with consecutive layers by geometrically partitioning each layer into sub-regions based on the area and the tissue scaffold design constraints. A continuous, interconnected and optimized tool-path for layers has been generated for a three-dimensional biomaterial deposition/printing process. A zigzag pattern tool-path has been proposed for an accumulated sub-region layer, and a concentric spiral-like optimal tool-path pattern has been generated for the successive layer to ensure continuity along the structure. Three-dimensional layers, formed by the proposed tool-path plan, vary the pore size and the porosity based on the biological and mechanical requirements. Several examples demonstrate the proposed methodology along with illustrative results. Also a comparative study between the proposed design and conventional Cartesian coordinate scaffolds has been performed. The results demonstrate a significant reduction in design error with the proposed method. Moreover, sample examples have been fabricated using a micro-nozzle biomaterial deposition system, and characterized for validation.

A functionally gradient variational porosity architecture for hollowed scaffolds fabrication.

Science.gov (United States)

Khoda, A K M; Ozbolat, Ibrahim T; Koc, Bahattin

2011-09-01

This paper presents a novel continuous tool-path planning methodology for hollowed scaffold fabrication in tissue engineering. A new functionally gradient porous architecture is proposed with a continuous material deposition planning scheme. A controllable variational pore size and hence the porosity have been achieved with a combination of two geometrically oriented consecutive layers. The desired porosity has been achieved with consecutive layers by geometrically partitioning each layer into sub-regions based on the area and the tissue scaffold design constraints. A continuous, interconnected and optimized tool-path for layers has been generated for a three-dimensional biomaterial deposition/printing process. A zigzag pattern tool-path has been proposed for an accumulated sub-region layer, and a concentric spiral-like optimal tool-path pattern has been generated for the successive layer to ensure continuity along the structure. Three-dimensional layers, formed by the proposed tool-path plan, vary the pore size and the porosity based on the biological and mechanical requirements. Several examples demonstrate the proposed methodology along with illustrative results. Also a comparative study between the proposed design and conventional Cartesian coordinate scaffolds has been performed. The results demonstrate a significant reduction in design error with the proposed method. Moreover, sample examples have been fabricated using a micro-nozzle biomaterial deposition system, and characterized for validation.

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.

Robust Adaptive Sliding Mode Consensus of Multiagent Systems with Perturbed Communications and Actuators

Directory of Open Access Journals (Sweden)

Xiao-Zheng Jin

2013-01-01

Full Text Available This paper deals with the asymptotic consensus problem for a class of multiagent systems with time-varying additive actuator faults and perturbed communications. The L2 performance of systems is also considered in the consensus controller designs. The upper and lower bounds of faults and perturbations in actuators and communications and controller gains are assumed to be unknown but can be estimated by designing some indirect adaptive laws. Based on the information from the adaptive estimation mechanism, the distributed robust adaptive sliding mode controllers are constructed to automatically compensate for the effects of faults and perturbations and to achieve any given level of L2 gain attenuation from external disturbance to consensus errors. Through Lyapunov functions and adaptive schemes, the asymptotic consensus of resulting adaptive multiagent system can be achieved with a specified performance criterion in the presence of perturbed communications and actuators. The effectiveness of the proposed design is illustrated via a decoupled longitudinal model of F-18 aircraft.

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.

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.

Consensus positive position feedback control for vibration attenuation of smart structures

Science.gov (United States)

Omidi, Ehsan; Nima Mahmoodi, S.

2015-04-01

This paper presents a new network-based approach for active vibration control in smart structures. In this approach, a network with known topology connects collocated actuator/sensor elements of the smart structure to one another. Each of these actuators/sensors, i.e., agent or node, is enhanced by a separate multi-mode positive position feedback (PPF) controller. The decentralized PPF controlled agents collaborate with each other in the designed network, under a certain consensus dynamics. The consensus constraint forces neighboring agents to cooperate with each other such that the disagreement between the time-domain actuation of the agents is driven to zero. The controller output of each agent is calculated using state-space variables; hence, optimal state estimators are designed first for the proposed observer-based consensus PPF control. The consensus controller is numerically investigated for a flexible smart structure, i.e., a thin aluminum beam that is clamped at its both ends. Results demonstrate that the consensus law successfully imposes synchronization between the independently controlled agents, as the disagreements between the decentralized PPF controller variables converge to zero in a short time. The new consensus PPF controller brings extra robustness to vibration suppression in smart structures, where malfunctions of an agent can be compensated for by referencing the neighboring agents’ performance. This is demonstrated in the results by comparing the new controller with former centralized PPF approach.

Polymer scaffolds bearing azobenzene - Potential for optical information storage

DEFF Research Database (Denmark)

Hvilsted, Søren; Ramanujam, P.S.

2001-01-01

% or greater, and erasability. The implications of the main chain nature for polyester morphology and for the permanency of the induced anisotropy are discussed. The design and methods of preparation of other significantly different polymer scaffolds supporting cyanoazobenzene are elaborated. Oligopeptides...

A collaborative platform for consensus sessions in pathology over Internet.

Science.gov (United States)

Zapletal, Eric; Le Bozec, Christel; Degoulet, Patrice; Jaulent, Marie-Christine

2003-01-01

The design of valid databases in pathology faces the problem of diagnostic disagreement between pathologists. Organizing consensus sessions between experts to reduce the variability is a difficult task. The TRIDEM platform addresses the issue to organize consensus sessions in pathology over the Internet. In this paper, we present the basis to achieve such collaborative platform. On the one hand, the platform integrates the functionalities of the IDEM consensus module that alleviates the consensus task by presenting to pathologists preliminary computed consensus through ergonomic interfaces (automatic step). On the other hand, a set of lightweight interaction tools such as vocal annotations are implemented to ease the communication between experts as they discuss a case (interactive step). The architecture of the TRIDEM platform is based on a Java-Server-Page web server that communicate with the ObjectStore PSE/PRO database used for the object storage. The HTML pages generated by the web server run Java applets to perform the different steps (automatic and interactive) of the consensus. The current limitations of the platform is to only handle a synchronous process. Moreover, improvements like re-writing the consensus workflow with a protocol such as BPML are already forecast.

Enhancing the Hydrophilicity and Cell Attachment of 3D Printed PCL/Graphene Scaffolds for Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Weiguang Wang

2016-12-01

Full Text Available Scaffolds are physical substrates for cell attachment, proliferation, and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements, i.e., certain standards in terms of mechanical properties, surface characteristics, porosity, degradability, and biocompatibility. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes, as well as surface treatment. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This paper investigates the use of an extrusion-based additive manufacturing system to produce poly(ε-caprolactone (PCL/pristine graphene scaffolds for bone tissue applications and the influence of chemical surface modification on their biological behaviour. Scaffolds with the same architecture but different concentrations of pristine graphene were evaluated from surface property and biological points of view. Results show that the addition of pristine graphene had a positive impact on cell viability and proliferation, and that surface modification leads to improved cell response.

Enhancing the Hydrophilicity and Cell Attachment of 3D Printed PCL/Graphene Scaffolds for Bone Tissue Engineering

Science.gov (United States)

Wang, Weiguang; Caetano, Guilherme; Ambler, William Stephen; Blaker, Jonny James; Frade, Marco Andrey; Mandal, Parthasarathi; Diver, Carl; Bártolo, Paulo

2016-01-01

Scaffolds are physical substrates for cell attachment, proliferation, and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements, i.e., certain standards in terms of mechanical properties, surface characteristics, porosity, degradability, and biocompatibility. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes, as well as surface treatment. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This paper investigates the use of an extrusion-based additive manufacturing system to produce poly(ε-caprolactone) (PCL)/pristine graphene scaffolds for bone tissue applications and the influence of chemical surface modification on their biological behaviour. Scaffolds with the same architecture but different concentrations of pristine graphene were evaluated from surface property and biological points of view. Results show that the addition of pristine graphene had a positive impact on cell viability and proliferation, and that surface modification leads to improved cell response. PMID:28774112

Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

Science.gov (United States)

Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

2017-11-01

. Current scaffolds often focus on providing sufficient mechanical support or bio-mimetic structure to promote cartilage repair. Thus, silk has been adopted and investigated broadly. However, inflammation is one of the most important factors in OA. But few scaffolds for cartilage repair reported anti-inflammation property. Meanwhile, chondroitin sulfate (CS) is a glycosaminoglycan present in the natural cartilage ECM, and has exhibited a number of useful biological properties including anti-inflammatory activity. Thus, we designed this silk-CS scaffold and proved that this scaffold exhibited good anti-inflammatory effects both in vitro and in vivo, promoted the repair of articular cartilage defect in animal model. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Thomas, Vinoy [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States); Zhang Xing [Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham (UAB), AL 35294 (United States); Catledge, Shane A [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States); Vohra, Yogesh K [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States)

2007-12-15

Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon (registered) ) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon (registered) scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 {+-} 0.42 MPa and a modulus of 15.44 {+-} 2.53 MPa with a failure strain of 322.5 {+-} 10% for a pure Maxon (registered) scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 {+-} 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon (registered) scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 {+-} 0.2 MPa and a modulus of 20.4 {+-} 3 MPa with a failure strain of 140 {+-} 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 {sup 0}C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery.

Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration

International Nuclear Information System (INIS)

Thomas, Vinoy; Zhang Xing; Catledge, Shane A; Vohra, Yogesh K

2007-01-01

Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon (registered) ) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon (registered) scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 ± 0.42 MPa and a modulus of 15.44 ± 2.53 MPa with a failure strain of 322.5 ± 10% for a pure Maxon (registered) scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 ± 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon (registered) scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 ± 0.2 MPa and a modulus of 20.4 ± 3 MPa with a failure strain of 140 ± 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 0 C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery

Graphene-augmented nanofiber scaffolds demonstrate new features in cells behaviour

Science.gov (United States)

Kazantseva, Jekaterina; Ivanov, Roman; Gasik, Michael; Neuman, Toomas; Hussainova, Irina

2016-07-01

Three-dimensional (3D) customized scaffolds capable to mimic a native extracellular matrix open new frontiers in cells manipulation and advanced therapy. The major challenge is in a proper substrate for in vitro models on engineered scaffolds, capable to modulate cells differentiation. Here for the first time we demonstrate novel design and functionality of the 3D porous scaffolds of aligned, self-assembled ceramic nanofibers of ultra-high anisotropy ratio (~107), augmented into graphene shells. This unique hybrid nano-network allows an exceptional combination of selective guidance stimuli of stem cells differentiation, immune reactions variations, and local immobilization of cancer cells, which was not available before. The scaffolds were shown to be able to direct human mesenchymal stem cells (important for stimulation of neuronal and muscle cells) preferential orientation, to suppress major inflammatory factors, and to localize cancer cells; all without additions of specific culture media. The selective downregulation of specific cytokines is anticipated as a new tool for understanding of human immune system and ways of treatment of associated diseases. The effects observed are self-regulated by cells only, without side effects, usually arising from use of external factors. New scaffolds may open new horizons for stem cells fate control such as towards axons and neurites regeneration (Alzheimer’s disease) as well as cancer therapy development.

Additively Manufactured Scaffolds for Bone Tissue Engineering and the Prediction of their Mechanical Behavior: A Review.

Science.gov (United States)

Zhang, Xiang-Yu; Fang, Gang; Zhou, Jie

2017-01-10

Additive manufacturing (AM), nowadays commonly known as 3D printing, is a revolutionary materials processing technology, particularly suitable for the production of low-volume parts with high shape complexities and often with multiple functions. As such, it holds great promise for the fabrication of patient-specific implants. In recent years, remarkable progress has been made in implementing AM in the bio-fabrication field. This paper presents an overview on the state-of-the-art AM technology for bone tissue engineering (BTE) scaffolds, with a particular focus on the AM scaffolds made of metallic biomaterials. It starts with a brief description of architecture design strategies to meet the biological and mechanical property requirements of scaffolds. Then, it summarizes the working principles, advantages and limitations of each of AM methods suitable for creating porous structures and manufacturing scaffolds from powdered materials. It elaborates on the finite-element (FE) analysis applied to predict the mechanical behavior of AM scaffolds, as well as the effect of the architectural design of porous structure on its mechanical properties. The review ends up with the authors' view on the current challenges and further research directions.

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.

Biocompatibility and biomechanical characteristics of loofah based scaffolds combined with hydroxyapatite, cellulose, poly-L-lactic acid with chondrocyte-like cells

International Nuclear Information System (INIS)

Cecen, Berivan; Kozaci, Leyla Didem; Yuksel, Mithat; Ustun, Ozcan; Ergur, Bekir Ugur; Havitcioglu, Hasan

2016-01-01

The current study reports the biocompatibility and biomechanical characteristics of loofah-based scaffolds combined with hydroxyapatite (HA), cellulose, poly-L-lactic acid (PLLA) with chondrocytes-like cells. Scanning electron microscope (SEM) micrographs of the scaffolds showed that the addition of PLLA usually resulted in an increase in cell's attachment on scaffolds. Mechanical and elemental analyzes were assessed using tensile test and Energy Dispersive X-ray spectrometry (EDS), respectively. In summary, we showed that the loofah + PLLA + HA scaffolds perform significantly better than other loofah–based scaffolds employed in terms of increasing a diversity of mechanical properties including tensile strength and Young's modulus. Based on the analysis of the differential scanning calorimetry (DSC) thermograms and EDS spectrums that give an idea about the calcium phosphate (CaP) ratios, the improvement in the mechanical properties could principally be recognized to the strong interaction formed between loofah, PLLA and HA. The viability of chondrocytes on loofah–based scaffolds was analyzed by XTT tests. However, none of the scaffolds have proved to be toxic in metabolic activity. The histological evaluation obtained by hematoxylin and eosin (H&E), Masson trichrome, toluidine blue and immunohistochemistry methods showed that cells in all scaffolds produced extracellular matrix that defined proteoglycan and type I-II collagens. The results of this study suggest that the loofah-based scaffold with desirable properties can be considered as an ideal candidate for cartilage tissue engineering applications. - Highlights: • In this study we designed a new scaffold and characterized it using biochemical and biomechanical assays. • Our manuscript with the novelty of the scaffold design will add new perspective in the literature about loofah based scaffolds. • The objective of the study is to investigate the natural and novel loofah based scaffolds with

Biocompatibility and biomechanical characteristics of loofah based scaffolds combined with hydroxyapatite, cellulose, poly-L-lactic acid with chondrocyte-like cells

Energy Technology Data Exchange (ETDEWEB)

Cecen, Berivan, E-mail: berivan.erik@deu.edu.tr [Dokuz Eylul University, The Institute of Health Science, Department of Biomechanics, 35340 Izmir (Turkey); Kozaci, Leyla Didem [Yildirim Beyazit University, Medical Faculty, Department of Medical Biochemistry, 06800 Ankara (Turkey); Yildirim Beyazit University, Musculoskeletal System Studies Research Center, 06800 Ankara (Turkey); Yuksel, Mithat [Ege University, Engineering Faculty, Department of Chemical Engineering, 35100 Izmir (Turkey); Ustun, Ozcan; Ergur, Bekir Ugur [Dokuz Eylul University, Department of Histology & Embryology, 35340 Izmir (Turkey); Havitcioglu, Hasan [Dokuz Eylul University, The Institute of Health Science, Department of Biomechanics, 35340 Izmir (Turkey); Dokuz Eylul University, Medicine Faculty, Department of Orthopaedics and Traumatology, 35340 Izmir (Turkey)

2016-12-01

The current study reports the biocompatibility and biomechanical characteristics of loofah-based scaffolds combined with hydroxyapatite (HA), cellulose, poly-L-lactic acid (PLLA) with chondrocytes-like cells. Scanning electron microscope (SEM) micrographs of the scaffolds showed that the addition of PLLA usually resulted in an increase in cell's attachment on scaffolds. Mechanical and elemental analyzes were assessed using tensile test and Energy Dispersive X-ray spectrometry (EDS), respectively. In summary, we showed that the loofah + PLLA + HA scaffolds perform significantly better than other loofah–based scaffolds employed in terms of increasing a diversity of mechanical properties including tensile strength and Young's modulus. Based on the analysis of the differential scanning calorimetry (DSC) thermograms and EDS spectrums that give an idea about the calcium phosphate (CaP) ratios, the improvement in the mechanical properties could principally be recognized to the strong interaction formed between loofah, PLLA and HA. The viability of chondrocytes on loofah–based scaffolds was analyzed by XTT tests. However, none of the scaffolds have proved to be toxic in metabolic activity. The histological evaluation obtained by hematoxylin and eosin (H&E), Masson trichrome, toluidine blue and immunohistochemistry methods showed that cells in all scaffolds produced extracellular matrix that defined proteoglycan and type I-II collagens. The results of this study suggest that the loofah-based scaffold with desirable properties can be considered as an ideal candidate for cartilage tissue engineering applications. - Highlights: • In this study we designed a new scaffold and characterized it using biochemical and biomechanical assays. • Our manuscript with the novelty of the scaffold design will add new perspective in the literature about loofah based scaffolds. • The objective of the study is to investigate the natural and novel loofah based scaffolds with

Flexible control of cellular encapsulation, permeability, and release in a droplet-templated bifunctional copolymer scaffold.

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Chen, Qiushui; Chen, Dong; Wu, Jing; Lin, Jin-Ming

2016-11-01

Designing cell-compatible, bio-degradable, and stimuli-responsive hydrogels is very important for biomedical applications in cellular delivery and micro-scale tissue engineering. Here, we report achieving flexible control of cellular microencapsulation, permeability, and release by rationally designing a diblock copolymer, alginate-conjugated poly(N-isopropylacrylamide) (Alg-co-PNiPAM). We use the microfluidic technique to fabricate the bifunctional copolymers into thousands of mono-disperse droplet-templated hydrogel microparticles for controlled encapsulation and triggered release of mammalian cells. In particular, the grafting PNiPAM groups in the synthetic cell-laden microgels produce lots of nano-aggregates into hydrogel networks at elevated temperature, thereafter enhancing the permeability of microparticle scaffolds. Importantly, the hydrogel scaffolds are readily fabricated via on-chip quick gelation by triggered release of Ca 2+ from the Ca-EDTA complex; it is also quite exciting that very mild release of microencapsulated cells is achieved via controlled degradation of hydrogel scaffolds through a simple strategy of competitive affinity of Ca 2+ from the Ca-Alginate complex. This finding suggests that we are able to control cellular encapsulation and release through ion-induced gelation and degradation of the hydrogel scaffolds. Subsequently, we demonstrate a high viability of microencapsulated cells in the microgel scaffolds.

Developing syndrome definitions based on consensus and current use

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Dowling, John N; Baer, Atar; Buckeridge, David L; Cochrane, Dennis; Conway, Michael A; Elkin, Peter; Espino, Jeremy; Gunn, Julia E; Hales, Craig M; Hutwagner, Lori; Keller, Mikaela; Larson, Catherine; Noe, Rebecca; Okhmatovskaia, Anya; Olson, Karen; Paladini, Marc; Scholer, Matthew; Sniegoski, Carol; Thompson, David; Lober, Bill

2010-01-01

Objective Standardized surveillance syndromes do not exist but would facilitate sharing data among surveillance systems and comparing the accuracy of existing systems. The objective of this study was to create reference syndrome definitions from a consensus of investigators who currently have or are building syndromic surveillance systems. Design Clinical condition–syndrome pairs were catalogued for 10 surveillance systems across the United States and the representatives of these systems were brought together for a workshop to discuss consensus syndrome definitions. Results Consensus syndrome definitions were generated for the four syndromes monitored by the majority of the 10 participating surveillance systems: Respiratory, gastrointestinal, constitutional, and influenza-like illness (ILI). An important element in coming to consensus quickly was the development of a sensitive and specific definition for respiratory and gastrointestinal syndromes. After the workshop, the definitions were refined and supplemented with keywords and regular expressions, the keywords were mapped to standard vocabularies, and a web ontology language (OWL) ontology was created. Limitations The consensus definitions have not yet been validated through implementation. Conclusion The consensus definitions provide an explicit description of the current state-of-the-art syndromes used in automated surveillance, which can subsequently be systematically evaluated against real data to improve the definitions. The method for creating consensus definitions could be applied to other domains that have diverse existing definitions. PMID:20819870

Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering.

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Paim, Ágata; Tessaro, Isabel C; Cardozo, Nilo S M; Pranke, Patricia

2018-03-05

Tissue engineering is a multidisciplinary field of research in which the cells, biomaterials, and processes can be optimized to develop a tissue substitute. Three-dimensional (3D) architectural features from electrospun scaffolds, such as porosity, tortuosity, fiber diameter, pore size, and interconnectivity have a great impact on cell behavior. Regarding tissue development in vitro, culture conditions such as pH, osmolality, temperature, nutrient, and metabolite concentrations dictate cell viability inside the constructs. The effect of different electrospun scaffold properties, bioreactor designs, mesenchymal stem cell culture parameters, and seeding techniques on cell behavior can be studied individually or combined with phenomenological modeling techniques. This work reviews the main culture and scaffold factors that affect tissue development in vitro regarding the culture of cells inside 3D matrices. The mathematical modeling of the relationship between these factors and cell behavior inside 3D constructs has also been critically reviewed, focusing on mesenchymal stem cell culture in electrospun scaffolds.

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.

3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration

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Derek H. Rosenzweig

2015-07-01

Full Text Available Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS and polylactic acid (PLA scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.

3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration.

Science.gov (United States)

Rosenzweig, Derek H; Carelli, Eric; Steffen, Thomas; Jarzem, Peter; Haglund, Lisbet

2015-07-03

Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.

Building bone tissue: matrices and scaffolds in physiology and biotechnology

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Riminucci M.

2003-01-01

Full Text Available Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies.

Custom-tailored tissue engineered polycaprolactone scaffolds for total disc replacement

International Nuclear Information System (INIS)

Van Uden, S; Silva-Correia, J; Correlo, V M; Oliveira, J M; Reis, R L

2015-01-01

Degeneration of the intervertebral disc (IVD) represents a significant musculoskeletal disease burden. Tissue engineering has proposed several strategies comprising the use of biodegradable materials to prepare scaffolds that can present mechanical properties similar to those of native IVD tissues. However, this might be insufficient, since the patient’s intervertebral space geometry must be replicated to allow for appropriate implant fixation and integration. Herein, we propose the use of reverse engineering and rapid prototyping techniques with the goal of preparing custom-tailored annulus fibrosus scaffolds; these techniques have previously been applied to rabbit models. The IVD reverse-engineered architecture was obtained by means of microcomputed tomography acquisition and three-dimensional modelling, resulting in a computer-aided design (CAD) that replicates the original rabbit IVD. Later, a fused deposition-modelling three-dimensional printer was used to produce the scaffolds with different geometries provided by the CAD, using polycaprolactone (PCL) with 100% infill density. The microstructure of the PCL scaffolds was investigated by scanning electron microscopy (SEM), which allowed us to observe an adequate fusion adhesion between the layers. The SEM images revealed that, up to the point of moderate resolution, the porosities manually designed in the CAD model were successfully replicated. The PCL scaffolds’ three-dimensional architecture was also assessed by means of microcomputed tomography analysis. Compressive stiffness was determined using a mechanical testing system. Results showed higher values than those of human IVDs (5.9–6.7 kN mm −1 versus 1.2 kN mm −1 , respectively). In vitro studies were performed to investigate the possible cytotoxicity of the polycaprolactone scaffolds’ leachables. The results showed that the custom-tailored PCL scaffolds do not have any deleterious cytotoxic effect over annulus fibrosus cells or the mouse lung

Distributed scaffolding: Wiki collaboration among Latino high school chemistry students

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O'Sullivan, Edwin Duncan, Jr.

The primary purpose of this study was to evaluate if wiki collaboration among Latino high school chemistry students can help reduce the science achievement gap between Latino and White students. The study was a quasi-experimental pre/post control group mixed-methods design. It used three intact sections of a high school chemistry course. The first research question asked if there is a difference in academic achievement between a treatment and control group on selected concepts from the topics of bonding, physical changes, and chemical changes, when Latino high school chemistry students collaborate on a quasi-natural wiki project. Overall results for all three activities (Bonding, Physical Changes, and Chemical Changes) indicated no significant difference between the wiki and control group. However, students performing the chemical changes activity did significantly better than their respective control group. Furthermore, there was a significant association, with large effect size, between group membership and ability to overcome the misconception that aqueous ionic reactants in precipitation reactions exist as molecular pairs of ions. Qualitative analysis of classroom and computer lab dialogue, discussion board communication, student focus groups, teacher interviews, and wiki content attributes the better performance of the chemical changes wiki group to favorable differences in intersubjectivity and calibrated assistance, as well as learning about submicroscopic representations of precipitation reactions in multiple contexts. Furthermore, the nonsignificant result overall points to an aversion to peer editing as a possible cause. Drawing considerably on Vygotsky and Piaget, the results are discussed within the context of how distributed scaffolding facilitated medium levels of cognitive conflict. The second research question asked what the characteristics of distributed metacognitive scaffolding are when Latino high school chemistry students collaborate on a quasi

Neuronal Networks on Nanocellulose Scaffolds.

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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.

Second-Order Multiagent Systems with Event-Driven Consensus Control

Directory of Open Access Journals (Sweden)

Jiangping Hu

2013-01-01

Full Text Available Event-driven control scheduling strategies for multiagent systems play a key role in future use of embedded microprocessors of limited resources that gather information and actuate the agent control updates. In this paper, a distributed event-driven consensus problem is considered for a multi-agent system with second-order dynamics. Firstly, two kinds of event-driven control laws are, respectively, designed for both leaderless and leader-follower systems. Then, the input-to-state stability of the closed-loop multi-agent system with the proposed event-driven consensus control is analyzed and the bound of the inter-event times is ensured. Finally, some numerical examples are presented to validate the proposed event-driven consensus control.

* Fabrication and Characterization of Biphasic Silk Fibroin Scaffolds for Tendon/Ligament-to-Bone Tissue Engineering.

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Font Tellado, Sònia; Bonani, Walter; Balmayor, Elizabeth R; Foehr, Peter; Motta, Antonella; Migliaresi, Claudio; van Griensven, Martijn

2017-08-01

Tissue engineering is an attractive strategy for tendon/ligament-to-bone interface repair. The structure and extracellular matrix composition of the interface are complex and allow for a gradual mechanical stress transfer between tendons/ligaments and bone. Thus, scaffolds mimicking the structural features of the native interface may be able to better support functional tissue regeneration. In this study, we fabricated biphasic silk fibroin scaffolds designed to mimic the gradient in collagen molecule alignment present at the interface. The scaffolds had two different pore alignments: anisotropic at the tendon/ligament side and isotropic at the bone side. Total porosity ranged from 50% to 80% and the majority of pores (80-90%) were ligament, enthesis, and cartilage markers significantly changed depending on pore alignment in each region of the scaffolds. In conclusion, the biphasic scaffolds fabricated in this study show promising features for tendon/ligament-to-bone tissue engineering.

Fragment virtual screening based on Bayesian categorization for discovering novel VEGFR-2 scaffolds.

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Zhang, Yanmin; Jiao, Yu; Xiong, Xiao; Liu, Haichun; Ran, Ting; Xu, Jinxing; Lu, Shuai; Xu, Anyang; Pan, Jing; Qiao, Xin; Shi, Zhihao; Lu, Tao; Chen, Yadong

2015-11-01

The discovery of novel scaffolds against a specific target has long been one of the most significant but challengeable goals in discovering lead compounds. A scaffold that binds in important regions of the active pocket is more favorable as a starting point because scaffolds generally possess greater optimization possibilities. However, due to the lack of sufficient chemical space diversity of the databases and the ineffectiveness of the screening methods, it still remains a great challenge to discover novel active scaffolds. Since the strengths and weaknesses of both fragment-based drug design and traditional virtual screening (VS), we proposed a fragment VS concept based on Bayesian categorization for the discovery of novel scaffolds. This work investigated the proposal through an application on VEGFR-2 target. Firstly, scaffold and structural diversity of chemical space for 10 compound databases were explicitly evaluated. Simultaneously, a robust Bayesian classification model was constructed for screening not only compound databases but also their corresponding fragment databases. Although analysis of the scaffold diversity demonstrated a very unevenly distribution of scaffolds over molecules, results showed that our Bayesian model behaved better in screening fragments than molecules. Through a literature retrospective research, several generated fragments with relatively high Bayesian scores indeed exhibit VEGFR-2 biological activity, which strongly proved the effectiveness of fragment VS based on Bayesian categorization models. This investigation of Bayesian-based fragment VS can further emphasize the necessity for enrichment of compound databases employed in lead discovery by amplifying the diversity of databases with novel structures.

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.

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

Science.gov (United States)

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

2012-09-01

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

A novel three-dimensional scaffold for regenerative endodontics: materials and biological characterizations.

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Bottino, Marco C; Yassen, Ghaeth H; Platt, Jeffrey A; Labban, Nawaf; Windsor, L Jack; Spolnik, Kenneth J; Bressiani, Ana H A

2015-11-01

An electrospun nanocomposite fibrous material holds promise as a scaffold, as well as a drug-delivery device to aid in root maturogenesis and the regeneration of the pulp-dentine complex. A novel three-dimensional (3D) nanocomposite scaffold composed of polydioxanone (PDS II®) and halloysite nanotubes (HNTs) was designed and fabricated by electrospinning. Morphology, structure, mechanical properties and cell compatibility studies were carried out to evaluate the effects of HNTs incorporation (0.5-10 wt% relative to PDS w/w). Overall, a 3D porous network was seen in the different fabricated electrospun scaffolds, regardless of the HNT content. The incorporation of HNTs at 10 wt% led to a significant (p endodontics. Copyright © 2013 John Wiley & Sons, Ltd.

Software scaffolds to promote regulation during scientific inquiry learning

NARCIS (Netherlands)

Manlove, S.A.; Lazonder, Adrianus W.; de Jong, Anthonius J.M.

2007-01-01

This research addresses issues in the design of online scaffolds for regulation within inquiry learning environments. The learning environment in this study included a physics simulation, data analysis tools, and a model editor for students to create runnable models. A regulative support tool called

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

Strontium eluting graphene hybrid nanoparticles augment osteogenesis in a 3D tissue scaffold

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Kumar, Sachin; Chatterjee, Kaushik

2015-01-01

The objective of this work was to prepare hybrid nanoparticles of graphene sheets decorated with strontium metallic nanoparticles and demonstrate their advantages in bone tissue engineering. Strontium-decorated reduced graphene oxide (RGO_Sr) hybrid nanoparticles were synthesized by the facile reduction of graphene oxide and strontium nitrate. X-ray diffraction, transmission electron microscopy, and atomic force microscopy revealed that the hybrid particles were composed of RGO sheets decorated with 200-300 nm metallic strontium particles. Thermal gravimetric analysis further confirmed the composition of the hybrid particles as 22 wt% of strontium. Macroporous tissue scaffolds were prepared by incorporating RGO_Sr particles in poly(ε-caprolactone) (PCL). The PCL/RGO_Sr scaffolds were found to elute strontium ions in aqueous medium. Osteoblast proliferation and differentiation was significantly higher in the PCL scaffolds containing the RGO_Sr particles in contrast to neat PCL and PCL/RGO scaffolds. The increased biological activity can be attributed to the release of strontium ions from the hybrid nanoparticles. This study demonstrates that composites prepared using hybrid nanoparticles that elute strontium ions can be used to prepare multifunctional scaffolds with good mechanical and osteoinductive properties. These findings have important implications for designing the next generation of biomaterials for use in tissue regeneration.The objective of this work was to prepare hybrid nanoparticles of graphene sheets decorated with strontium metallic nanoparticles and demonstrate their advantages in bone tissue engineering. Strontium-decorated reduced graphene oxide (RGO_Sr) hybrid nanoparticles were synthesized by the facile reduction of graphene oxide and strontium nitrate. X-ray diffraction, transmission electron microscopy, and atomic force microscopy revealed that the hybrid particles were composed of RGO sheets decorated with 200-300 nm metallic strontium

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

3D Printed, PVA–PAA Hydrogel Loaded-Polycaprolactone Scaffold for the Delivery of Hydrophilic In-Situ Formed Sodium Indomethacin

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Mershen Govender

2018-06-01

Full Text Available 3D printed polycaprolactone (PCL-blended scaffolds have been designed, prepared, and evaluated in vitro in this study prior to the incorporation of a polyvinyl alcohol–polyacrylic acid (PVA–PAA hydrogel for the delivery of in situ-formed sodium indomethacin. The prepared PCL–PVA–PAA scaffold is proposed as a potential structural support system for load-bearing tissue damage where inflammation is prevalent. Uniaxial strain testing of the PCL-blended scaffolds were undertaken to determine the scaffold’s resistance to strain in addition to its thermal, structural, and porosimetric properties. The viscoelastic properties of the incorporated PVA–PAA hydrogel has also been determined, as well as the drug release profile of the PCL–PVA–PAA scaffold. Results of these analyses noted the structural strength, thermal stability, and porosimetric properties of the scaffold, as well as the ability of the PCL–PVA–PAA scaffold to deliver sodium indomethacin in simulated physiological conditions of pH and temperature. The results of this study therefore highlight the successful design, fabrication, and in vitro evaluation of a 3D printed polymeric strain-resistant supportive platform for the delivery of sodium indomethacin.

Dispensing-based bioprinting of mechanically-functional hybrid scaffolds with vessel-like channels for tissue engineering applications - A brief review.

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Naghieh, Saman; Sarker, Md; Izadifar, Mohammad; Chen, Xiongbiao

2018-02-01

Over the past decades, significant progress has been achieved in the field of tissue engineering (TE) to restore/repair damaged tissues or organs and, in this regard, scaffolds made from biomaterials have played a critical role. Notably, recent advances in biomaterials and three-dimensional (3D) printing have enabled the manipulation of two or more biomaterials of distinct, yet complementary, mechanical and/or biological properties to form so-called hybrid scaffolds mimicking native tissues. Among various biomaterials, hydrogels synthesized to incorporate living cells and/or biological molecules have dominated due to their hydrated tissue-like environment. Moreover, dispensing-based bioprinting has evolved to the point that it can now be used to create hybrid scaffolds with complex structures. However, the complexities associated with multi-material bioprinting and synthesis of hydrogels used for hybrid scaffolds pose many challenges for their fabrication. This paper presents a brief review of dispensing-based bioprinting of hybrid scaffolds for TE applications. The focus is on the design and fabrication of hybrid scaffolds, including imaging techniques, potential biomaterials, physical architecture, mechanical properties, cell viability, and the importance of vessel-like channels. The key issues and challenges for dispensing-based bioprinting of hybrid scaffolds are also identified and discussed along with recommendations for future research directions. Addressing these issues will significantly enhance the design and fabrication of hybrid scaffolds to and pave the way for translating them into clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

A three-dimensional hierarchical collagen scaffold fabricated by a combined solid freeform fabrication (SFF) and electrospinning process to enhance mesenchymal stem cell (MSC) proliferation

International Nuclear Information System (INIS)

Ahn, SeungHyun; Kim, GeunHyung; Koh, Young Ho

2010-01-01

Collagen has the advantage of being very similar to macromolecular substances that can be recognized and metabolized in the biological environment. Although the natural material has superior property for this purpose, its use to fabricate reproducible and pore-structure-controlled 3D structures, which are designed to allow the entry of sufficient cells and the easy diffusion of nutrients, has been limited due to its low processability. Here, we propose a hybrid technology that combines a cryogenic plotting system with an electrospinning process. Using this technique, an easily pore-size-controllable hierarchical 3D scaffold consisting of micro-sized highly porous collagen strands and micro/nano-sized collagen fibers was fabricated. The pore structure of the collagen scaffold was controlled by the collagen micro/nanofibers, which were layered in the scaffold. The hierarchical scaffolds were characterized with respect to initial cell attachment and proliferation of bone marrow-derived mesenchymal stem cells within the scaffolds. The hierarchical scaffold exhibited incredibly enhanced initial cell attachment and cell compactness between pores of the plotted scaffold relative to the normally designed 3D collagen scaffold.

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

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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.

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering.

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Wysocki, Bartłomiej; Idaszek, Joanna; Szlązak, Karol; Strzelczyk, Karolina; Brynk, Tomasz; Kurzydłowski, Krzysztof J; Święszkowski, Wojciech

2016-03-15

Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM) methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds' morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium) was used to design a porous scaffolds with pore size equal to (A) 200 µm, (B) 500 µm and (C) 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti) using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany). The selective laser melting (SLM) process was optimized and the laser beam energy density in range of 91-151 J/mm³ was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO₃ acid solutions. Based on scaffolds mass loss and scanning electron (SEM) observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT) and SEM images. The mechanical tests showed that the treated scaffolds had Young's modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes.

Feasibility of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold for cartilage tissue engineering.

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Tang, Cheng; Xu, Yan; Jin, Chengzhe; Min, Byoung-Hyun; Li, Zhiyong; Pei, Xuan; Wang, Liming

2013-12-01

Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the current ECM materials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologous ECM scaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell-derived ECM (aBMSC-dECM) membrane was collected and fabricated into a three-dimensional porous scaffold via cross-linking and freeze-drying techniques. Articular chondrocytes were seeded into the aBMSC-dECM scaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that the aBMSC-dECM scaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in the aBMSC-dECM scaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on the aBMSC-dECM scaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that the aBMSC-dECM scaffold could be a successful novel candidate scaffold for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

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.

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

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

2016-09-01

necessary to understand their biophysical behavior in vivo. In this work, the relationship between morphology and physical properties in the dry and hydrated states was investigated across a range of solid concentrations in the scaffolds. The quantitative results provided can aid the design of scaffolds with a target trade-off between mechanical properties and structural features important for their biological activity. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Optimizing Segmental Bone Regeneration Using Functionally Graded Scaffolds

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2012-10-01

mechanical strength (130– 190 MPa).4 Cancellous bone accounts for the other 20% of the total bone mass and is highly porous (50%–90%), with *10% of the...bionanotechnology. Adv Mater 18, 1345, 2006. 96. Drury , J.L., and Mooney, D.J. Hydrogels for tissue engi- neering: scaffold design variables and applications. Bio

Bipartite consensus for multi-agent systems with antagonistic interactions and communication delays

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Guo, Xing; Lu, Jianquan; Alsaedi, Ahmed; Alsaadi, Fuad E.

2018-04-01

This paper studies the consensus problems over signed digraphs with arbitrary finite communication delays. For the considered system, the information flow is directed and only locally delayed information can be used for each node. We derive that bipartite consensus of this system can be realized when the associated signed digraph is strongly connected. Furthermore, for structurally balanced networks, this paper studies the pinning partite consensus for the considered system. we design a pinning scheme to pin any one agent in the signed network, and obtain that the network achieves pinning bipartite consensus with any initial conditions. Finally, two examples are provided to demonstrate the effectiveness of our main results.

A Facile and Eco-friendly Route to Fabricate Poly(Lactic Acid) Scaffolds with Graded Pore Size.

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Scaffaro, Roberto; Lopresti, Francesco; Botta, Luigi; Maio, Andrea; Sutera, Fiorenza; Mistretta, Maria Chiara; La Mantia, Francesco Paolo

2016-10-17

Over the recent years, functionally graded scaffolds (FGS) gaineda crucial role for manufacturing of devices for tissue engineering. The importance of this new field of biomaterials research is due to the necessity to develop implants capable of mimicking the complex functionality of the various tissues, including a continuous change from one structure or composition to another. In this latter context, one topic of main interest concerns the design of appropriate scaffolds for bone-cartilage interface tissue. In this study, three-layered scaffolds with graded pore size were achieved by melt mixing poly(lactic acid) (PLA), sodium chloride (NaCl) and polyethylene glycol (PEG). Pore size distributions were controlled by NaCl granulometry and PEG solvation. Scaffolds were characterized from a morphological and mechanical point of view. A correlation between the preparation method, the pore architecture and compressive mechanical behavior was found. The interface adhesion strength was quantitatively evaluated by using a custom-designed interfacial strength test. Furthermore, in order to imitate the human physiology, mechanical tests were also performed in phosphate buffered saline (PBS) solution at 37 °C. The method herein presented provides a high control of porosity, pore size distribution and mechanical performance, thus offering the possibility to fabricate three-layered scaffolds with tailored properties by following a simple and eco-friendly route.

Platelet lysate embedded scaffolds for skin regeneration.

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

2015-04-01

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

Semiotic Scaffolding in Mathematics

DEFF Research Database (Denmark)

Johansen, Mikkel Willum; Misfeldt, Morten

2015-01-01

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

FGL-functionalized self-assembling nanofiber hydrogel as a scaffold for spinal cord-derived neural stem cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Jian [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng, Jin [Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qixin, E-mail: zheng-qx@163.com [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Wu, Yongchao; Wu, Bin; Huang, Shuai; Fang, Weizhi; Guo, Xiaodong [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

2015-01-01

A class of designed self-assembling peptide nanofiber scaffolds has been shown to be a good biomimetic material in tissue engineering. Here, we specifically made a new peptide hydrogel scaffold FGLmx by mixing the pure RADA{sub 16} and designer functional peptide RADA{sub 16}-FGL solution, and we analyzed the physiochemical properties of each peptide with atomic force microscopy (AFM) and circular dichroism (CD). In addition, we examined the biocompatibility and bioactivity of FGLmx as well as RADA{sub 16} scaffold on spinal cord-derived neural stem cells (SC-NSCs) isolated from neonatal rats. Our results showed that RADA{sub 16}-FGL displayed a weaker β-sheet structure and FGLmx could self-assemble into nanofibrous morphology. Moreover, we found that FGLmx was not only noncytotoxic to SC-NSCs but also promoted SC-NSC proliferation and migration into the three-dimensional (3-D) scaffold, meanwhile, the adhesion and lineage differentiation of SC-NSCs on FGLmx were similar to that on RADA{sub 16}. Our results indicated that the FGL-functionalized peptide scaffold might be very beneficial for tissue engineering and suggested its further application for spinal cord injury (SCI) repair. - Highlights: • RADA{sub 16} and RADA{sub 16}-FGL peptides were synthesized and characterized. • Rat spinal cord neural stem cells were successfully isolated and characterized. • We provided an induction method for mixed differentiation of neural stem cells. • FGL scaffold had good biocompatibility and bioactivity with neural stem cells.

Fluorescent composite scaffolds made of nanodiamonds/polycaprolactone

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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.

Fabrication of a customized bone scaffold using a homemade medical 3D printer for comminuted fractures

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Yoon, Do-Kun; Jung, Joo-Young; Shin, Han-Back; Kim, Moo-Sub; Choe, Bo-Young; Kim, Sunmi; Suh, Tae Suk; Lee, Keum Sil; Xing, Lei

2016-09-01

The purpose of this study was to show a 3D printed reconstruction model of a bone destroyed by a comminuted fracture. After a thoracic limb of a cow with a comminuted fracture was scanned by using computed tomography, a scaffold was designed by using a 3D modeling tool for its reconstruction and fabricated by using a homemade medical 3D printer. The homemade medical 3D printer was designed for medical use. In order to reconstruct the geometry of the destroyed bone, we use the geometry of a similar section (reference geometry) of normal bone in the 3D modeling process. The missing part between the destroyed ridge and the reference geometry was filled with an effective space by using a manual interpolation. Inexpensive materials and free software were used to construct the medical 3D printer system. The fabrication of the scaffold progressed according to the design of reconstructed bone by using this medical 3D printer. The material of the scaffold was biodegradable material, and could be transplanted into the human body. The fabricated scaffold was correctly inserted into the fractured bone in place of the destroyed portion, with good agreement. According to physical stress test results, the performance of printing resolution was 0.1 mm. The average geometrical error of the scaffold was below 0.3 mm. The reconstructed bone by using the fabricated scaffold was able to support the weight of the human body. No process used to obtain the result was complex or required many resources. The methods and results in this study show several possible clinical applications in fields such as orthopedics or oncology without a need to purchase high-price instruments for 3D printing.

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.

PENGARUH E-SCAFFOLDING DALAM THINK PAIR SHARE TERHADAP KEMAMPUAN BERPIKIR TINGKAT TINGGI DINAMIKA PARTIKEL

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Akhmad Fauzul Albab

2016-01-01

Full Text Available Abstract: This study aimed to examine the effect of e-learning based Think Pair Share cooperative learning model toward higher order thinking skills of students. This study was conducted at SMAN 1 Jember for X grade students and used factorial design. Two experimental groups (TPS with E-Scaffolding and TPS with scaffolding were compared with a control group (TPS. This research was carried out to 180 students. The results showed that there is a difference in high-order thinking skills among groups of students who take the e-scaffolding in the TPS, scaffolding in TPS, and TPS learning; there is a difference in high-order thinking skills among groups of students with different prior knowledge levels; and there is no interactional effect among e-scaffolding in TPS, scaffolding in TPS and TPS strategy and the student’s prior knowledge on high order thinking skills. Key words: e-scaffolding, think pair share, high order thinking, prior knowledge.                                                                                     Abstrak: Penelitian ini bertujuan untuk menguji pengaruh pembelajaran berbasis e-learning yang terintegrasi dalam model pembelajaran kooperatif Think Pair Share (TPS dalam bentuk E-Scaffolding terhadap kemampuan berpikir tingkat tinggi siswa. Penelitian dilaksanakan di SMA Negeri 1 Jember untuk siswa kelas X ini dengan menggunakan rancangan faktorial. Dua kelompok eksperimen (TPS dengan E-Scaffolding dan TPS dengan Scaffolding dibandingkan dengan sebuah kelompok kontrol (TPS. Penelitian dilaksanakan terhadap sampel sebanyak 180 siswa yang dipilih secara acak kelompok. Hasil penelitian menunjukkan bahwa terdapat perbedaan kemampuan berpikir tingkat tinggi antara kelompok siswa yang mengikuti pembelajaran e-scaffolding dalam TPS dengan pembelajaran scaffolding dalam TPS maupun siswa dengan pembelajaran TPS; terdapat perbedaan kemampuan berpikir

[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

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.

De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Science.gov (United States)

Potin, Dominique; Launay, Michele; Nicolai, Eric; Fabreguette, Maud; Malabre, Patrice; Caussade, François; Besse, Dominique; Skala, Stacey; Stetsko, Dawn K; Todderud, Gordon; Beno, Brett R; Cheney, Daniel L; Chang, Chiehying J; Sheriff, Steven; Hollenbaugh, Diane L; Barrish, Joel C; Iwanowicz, Edwin J; Suchard, Suzanne J; Dhar, T G Murali

2005-02-15

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery.

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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.

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

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

International Nuclear Information System (INIS)

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-01-01

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds. (paper)

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

Science.gov (United States)

Holmes, Benjamin; Bulusu, Kartik; Plesniak, Michael; Zhang, Lijie Grace

2016-02-01

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

BESST--efficient scaffolding of large fragmented assemblies.

Science.gov (United States)

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

2014-08-15

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

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.

[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.

A Method for Consensus Reaching in Product Kansei Evaluation Using Advanced Particle Swarm Optimization.

Science.gov (United States)

Yang, Yan-Pu

2017-01-01

Consumers' opinions toward product design alternatives are often subjective and perceptual, which reflect their perception about a product and can be described using Kansei adjectives. Therefore, Kansei evaluation is often employed to determine consumers' preference. However, how to identify and improve the reliability of consumers' Kansei evaluation opinions toward design alternatives has an important role in adding additional insurance and reducing uncertainty to successful product design. To solve this problem, this study employs a consensus model to measure consistence among consumers' opinions, and an advanced particle swarm optimization (PSO) algorithm combined with Linearly Decreasing Inertia Weight (LDW) method is proposed for consensus reaching by minimizing adjustment of consumers' opinions. Furthermore, the process of the proposed method is presented and the details are illustrated using an example of electronic scooter design evaluation. The case study reveals that the proposed method is promising for reaching a consensus through searching optimal solutions by PSO and improving the reliability of consumers' evaluation opinions toward design alternatives according to Kansei indexes.

Toward a Framework on How Affordances and Motives Can Drive Different Uses of Scaffolds: Theory, Evidence, and Design Implications

Science.gov (United States)

Belland, Brian R.; Drake, Joel

2013-01-01

One way to help students engage in higher-order thinking is through scaffolding, which can be defined as support that allows students to participate meaningfully in and gain skill at a task that is beyond their unassisted abilities. Most research on computer-based scaffolds assesses the average impact of the tools on learning outcomes. This is…

Biomechanical properties of 3D-printed bone scaffolds are improved by treatment with CRFP.

Science.gov (United States)

Helguero, Carlos G; Mustahsan, Vamiq M; Parmar, Sunjit; Pentyala, Sahana; Pfail, John L; Kao, Imin; Komatsu, David E; Pentyala, Srinivas

2017-12-22

One of the major challenges in orthopedics is to develop implants that overcome current postoperative problems such as osteointegration, proper load bearing, and stress shielding. Current implant techniques such as allografts or endoprostheses never reach full bone integration, and the risk of fracture due to stress shielding is a major concern. To overcome this, a novel technique of reverse engineering to create artificial scaffolds was designed and tested. The purpose of the study is to create a new generation of implants that are both biocompatible and biomimetic. 3D-printed scaffolds based on physiological trabecular bone patterning were printed. MC3T3 cells were cultured on these scaffolds in osteogenic media, with and without the addition of Calcitonin Receptor Fragment Peptide (CRFP) in order to assess bone formation on the surfaces of the scaffolds. Integrity of these cell-seeded bone-coated scaffolds was tested for their mechanical strength. The results show that cellular proliferation and bone matrix formation are both supported by our 3D-printed scaffolds. The mechanical strength of the scaffolds was enhanced by trabecular patterning in the order of 20% for compression strength and 60% for compressive modulus. Furthermore, cell-seeded trabecular scaffolds modulus increased fourfold when treated with CRFP. Upon mineralization, the cell-seeded trabecular implants treated with osteo-inductive agents and pretreated with CRFP showed a significant increase in the compressive modulus. This work will lead to creating 3D structures that can be used in the replacement of not only bone segments, but entire bones.

Community consensus: Design beyond participation

CSIR Research Space (South Africa)

Winschiers-Theophilus, H

2012-07-01

Full Text Available is critical to design, and in particular, to cross-cultural design. Societies and groups based on other value systems conceptualize "participation" differently, and this understanding directly affects the intercultural design process. Thus, we explore...

Inverse Opal Scaffolds and Their Biomedical Applications.

Science.gov (United States)

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

2017-09-01

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

Inverse Opal Scaffolds with Gradations in Mineral Content for Spatial Control of Osteogenesis.

Science.gov (United States)

Zhu, Chunlei; Qiu, Jichuan; Pongkitwitoon, Suphannee; Thomopoulos, Stavros; Xia, Younan

2018-05-30

The design and fabrication of inverse opal scaffolds with gradations in mineral content to achieve spatial control of osteogenesis are described. The gradient in mineral content is established via the diffusion-limited transport of hydroxyapatite nanoparticles in a closely packed lattice of gelatin microbeads. The mineral-graded scaffold has an array of uniform pores and interconnected windows to facilitate efficient transport of nutrients and metabolic wastes, ensuring high cell viability. The graded distribution of mineral content can provide biochemical and mechanical cues for spatially regulating the osteogenic differentiation of adipose-derived stromal cells. This new class of scaffolds holds promise for engineering the interfaces between mineralized and unmineralized tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In silico simulation and in vitro evaluation of an elastomeric scaffold using ultrasonic shear wave imaging

Science.gov (United States)

Yu, Jiao; Nie, Erwei; Zhu, Yanying; Hong, Yi

2018-03-01

Biodegradable elastomeric scaffolds for soft tissue repair represent a growing area of biomaterials research. Mechanical strength is one of the key factors to consider in the evaluation of candidate materials and the designs for tissue scaffolds. It is desirable to develop non-invasive evaluation methods of the mechanical property of scaffolds which would provide options for monitoring temporal mechanical property changes in situ. In this paper, we conduct in silico simulation and in vitro evaluation of an elastomeric scaffold using a novel ultrasonic shear wave imaging (USWI). The scaffold is fabricated from a biodegradable elastomer, poly(carbonate urethane) urea using salt leaching method. A numerical simulation is performed to test the robustness of the developed inversion algorithm for the elasticity map reconstruction which will be implemented in the phantom experiment. The generation and propagation of shear waves in a homogeneous tissue-mimicking medium with a circular scaffold inclusion is simulated and the elasticity map is well reconstructed. A PVA phantom experiment is performed to test the ability of USWI combined with the inversion algorithm to non-invasively characterize the mechanical property of a porous, biodegradable elastomeric scaffold. The elastic properties of the tested scaffold can be easily differentiated from the surrounding medium in the reconstructed image. The ability of the developed method to identify the edge of the scaffold and characterize the elasticity distribution is demonstrated. Preliminary results in this pilot study support the idea of applying the USWI based method for non-invasive elasticity characterization of tissue scaffolds.

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.

Science.gov (United States)

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

2010-05-01

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

Effect of Ceramic Scaffold Architectural Parameters on Biological Response

Directory of Open Access Journals (Sweden)

Maria Isabella eGariboldi

2015-10-01

Full Text Available Numerous studies have focused on the optimization of ceramic architectures to fulfill a variety of scaffold functional requirements and improve biological response. Conventional fabrication techniques, however, do not allow for the production of geometrically controlled, reproducible structures and often fail to allow the independent variation of individual geometric parameters. Current developments in additive manufacturing technologies suggest that 3D printing will allow a more controlled and systematic exploration of scaffold architectures. This more direct translation of design into structure requires a pipeline for design-driven optimization. A theoretical framework for systematic design and evaluation of architectural parameters on biological response is presented. Four levels of architecture are considered, namely (1 surface topography, (2 pore size and geometry, (3 porous networks and (4 macroscopic pore arrangement, including the potential for spatially varied architectures. Studies exploring the effect of various parameters within these levels are reviewed. This framework will hopefully allow uncovering of new relationships between architecture and biological response in a more systematic way, as well as inform future refinement of fabrication techniques to fulfill architectural necessities with a consideration of biological implications.

SOS: Observation, Intervention, and Scaffolding towards Successful Online Students

Science.gov (United States)

Ainsa, Trisha

2017-01-01

Research, reflection, and evaluation of online classes indicated a need for graduated scaffolding for first time students experiencing distance learning. In order to promote student engagement in the online learning process, I designed SOS for beginning online students. Sixty-three online students were offered an opportunity to participate in a…

Preparation of bioactive porous HA/PCL composite scaffolds

Energy Technology Data Exchange (ETDEWEB)

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

2008-12-30

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

Polyelectrolyte-complex nanostructured fibrous scaffolds for tissue engineering

International Nuclear Information System (INIS)

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

2009-01-01

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

Preparation of bioactive porous HA/PCL composite scaffolds

International Nuclear Information System (INIS)

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

2008-01-01

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

Delivery of S1P receptor-targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect.

Science.gov (United States)

Das, Anusuya; Tanner, Shaun; Barker, Daniel A; Green, David; Botchwey, Edward A

2014-04-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro-computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Delivery of S1P Receptor-Targeted Drugs via Biodegradable Polymer Scaffolds Enhances Bone Regeneration in a Critical Size Cranial Defect*

Science.gov (United States)

Das, Anusuya; Tanner, Shaun; Barker, Daniel A.; Green, David; Botchwey, Edward A.

2014-01-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with microcomputed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. PMID:23640833

Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: A review.

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Wang, Xiaojian; Xu, Shanqing; Zhou, Shiwei; Xu, Wei; Leary, Martin; Choong, Peter; Qian, M; Brandt, Milan; Xie, Yi Min

2016-03-01

One of the critical issues in orthopaedic regenerative medicine is the design of bone scaffolds and implants that replicate the biomechanical properties of the host bones. Porous metals have found themselves to be suitable candidates for repairing or replacing the damaged bones since their stiffness and porosity can be adjusted on demands. Another advantage of porous metals lies in their open space for the in-growth of bone tissue, hence accelerating the osseointegration process. The fabrication of porous metals has been extensively explored over decades, however only limited controls over the internal architecture can be achieved by the conventional processes. Recent advances in additive manufacturing have provided unprecedented opportunities for producing complex structures to meet the increasing demands for implants with customized mechanical performance. At the same time, topology optimization techniques have been developed to enable the internal architecture of porous metals to be designed to achieve specified mechanical properties at will. Thus implants designed via the topology optimization approach and produced by additive manufacturing are of great interest. This paper reviews the state-of-the-art of topological design and manufacturing processes of various types of porous metals, in particular for titanium alloys, biodegradable metals and shape memory alloys. This review also identifies the limitations of current techniques and addresses the directions for future investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Azobenzene Optical Storage Puzzle - Demands on the Polymer Scaffold?

DEFF Research Database (Denmark)

Hvilsted, Søren; Ramanujam, PS

2001-01-01

of the nature of the main chain on polyester morphology and on the permanency of the induced anisotropy are discussed. Arguments for the design and methods of preparation of other very different polymer scaffolds supporting the cyanoazobenzene are elucidated. Whereas oligopeptides invariably form amorphous...

The azobenzene optical storage puzzle - Demands on the polymer scaffold?

DEFF Research Database (Denmark)

Hvilsted, Søren; Ramanujam, P.S.

2001-01-01

of the nature of the main chain on polyester morphology and on the permanency of the induced anisotropy are discussed. Arguments for the design and methods of preparation of other very different polymer scaffolds supporting the cyanoazobenzene are elucidated. Whereas oligopeptides invariably form amorphous...

Distributed Leader-Following Finite-Time Consensus Control for Linear Multiagent Systems under Switching Topology

Science.gov (United States)

Xu, Xiaole; Chen, Shengyong

2014-01-01

This paper investigates the finite-time consensus problem of leader-following multiagent systems. The dynamical models for all following agents and the leader are assumed the same general form of linear system, and the interconnection topology among the agents is assumed to be switching and undirected. We mostly consider the continuous-time case. By assuming that the states of neighbouring agents are known to each agent, a sufficient condition is established for finite-time consensus via a neighbor-based state feedback protocol. While the states of neighbouring agents cannot be available and only the outputs of neighbouring agents can be accessed, the distributed observer-based consensus protocol is proposed for each following agent. A sufficient condition is provided in terms of linear matrix inequalities to design the observer-based consensus protocol, which makes the multiagent systems achieve finite-time consensus under switching topologies. Then, we discuss the counterparts for discrete-time case. Finally, we provide an illustrative example to show the effectiveness of the design approach. PMID:24883367

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Bartłomiej Wysocki

2016-03-01

Full Text Available Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds’ morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium was used to design a porous scaffolds with pore size equal to (A 200 µm, (B 500 µm and (C 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany. The selective laser melting (SLM process was optimized and the laser beam energy density in range of 91–151 J/mm3 was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO3 acid solutions. Based on scaffolds mass loss and scanning electron (SEM observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT and SEM images. The mechanical tests showed that the treated scaffolds had Young’s modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes.

Fabrication of channeled scaffolds with ordered array of micro-pores through microsphere leaching and indirect Rapid Prototyping technique.

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Tan, J Y; Chua, C K; Leong, K F

2013-02-01

Advanced scaffold fabrication techniques such as Rapid Prototyping (RP) are generally recognized to be advantageous over conventional fabrication methods in terms architectural control and reproducibility. Yet, most RP techniques tend to suffer from resolution limitations which result in scaffolds with uncontrollable, random-size pores and low porosity, albeit having interconnected channels which is characteristically present in most RP scaffolds. With the increasing number of studies demonstrating the profound influences of scaffold pore architecture on cell behavior and overall tissue growth, a scaffold fabrication method with sufficient architectural control becomes imperative. The present study demonstrates the use of RP fabrication techniques to create scaffolds having interconnected channels as well as controllable micro-size pores. Adopted from the concepts of porogen leaching and indirect RP techniques, the proposed fabrication method uses monodisperse microspheres to create an ordered, hexagonal closed packed (HCP) array of micro-pores that surrounds the existing channels of the RP scaffold. The pore structure of the scaffold is shaped using a single sacrificial construct which comprises the microspheres and a dissolvable RP mold that were sintered together. As such, the size of pores as well as the channel configuration of the scaffold can be tailored based on the design of the RP mold and the size of microspheres used. The fabrication method developed in this work can be a promising alternative way of preparing scaffolds with customized pore structures that may be required for specific studies concerning cell-scaffold interactions.

Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells.

Science.gov (United States)

Subramanian, A; Ranganathan, P; Diamond, S L

1999-09-01

Lipofection of nondividing cells is inefficient because much of the transfected DNA is retained in endosomes, and that which escapes to the cytoplasm enters the nucleus at low rates. To improve the final rate-limiting step of nuclear import, we conjugated a nonclassical nuclear localization signal (NLS) containing the M9 sequence of heterogeneous nuclear ribonucleoprotein (hnRNP) A1, to a cationic peptide scaffold derived from a scrambled sequence of the SV40 T-antigen consensus NLS (ScT). The ScT was added to improve DNA binding of the M9 sequence. Lipofection of confluent endothelium with plasmid complexed with the M9-ScT conjugate resulted in 83% transfection and a 63-fold increase in marker gene expression. The M9-ScT conjugate localized fluorescent plasmid into the nucleus of permeabilized cells, and addition of the nuclear pore blocker wheat germ agglutinin prevented nuclear import. This method of gene transfer may lead to viral- and lipid-free transfection of nondividing cells.

Strategic Design and Fabrication of Biomimetic 3D Scaffolds: Unique Architectures of Extracellular Matrices for Enhanced Adipogenesis and Soft Tissue Reconstruction.

Science.gov (United States)

Unnithan, Afeesh Rajan; Sasikala, Arathyram Ramachandra Kurup; Thomas, Shalom Sara; Nejad, Amin Ghavami; Cha, Youn Soo; Park, Chan Hee; Kim, Cheol Sang

2018-04-09

The higher rate of soft tissue impairment due to lumpectomy or other trauma greatly requires the restoration of the irreversibly lost subcutaneous adipose tissues. The nanofibers fabricated by conventional electrospinning provide only a superficial porous structure due to its sheet like 2D structure and thereby hinder the cell infiltration and differentiation throughout the scaffolds. Thus we developed a novel electrospun 3D membrane using the zwitterionic poly (carboxybetaine-co-methyl methacrylate) co-polymer (CMMA) through electrostatic repulsion based electrospinning for soft tissue engineering. The inherent charges in the CMMA will aid the nanofiber to directly transform into a semiconductor and thereby transfer the immense static electricity from the grounded collector and will impart greater fluffiness to the scaffolds. The results suggest that the fabricated 3D nanofiber (CMMA 3NF) scaffolds possess nanofibers with larger inter connected pores and less dense structure compared to the conventional 2D scaffolds. The CMMA 3NF exhibits significant cues of soft tissue engineering such as enhanced biocompatibility as well as the faster regeneration of cells. Moreover the fabricated 3D scaffolds greatly assist the cells to develop into its stereoscopic topographies with an enhanced adipogenic property.

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.

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.

Sampled-Data Consensus of Linear Multi-agent Systems With Packet Losses.

Science.gov (United States)

Zhang, Wenbing; Tang, Yang; Huang, Tingwen; Kurths, Jurgen

In this paper, the consensus problem is studied for a class of multi-agent systems with sampled data and packet losses, where random and deterministic packet losses are considered, respectively. For random packet losses, a Bernoulli-distributed white sequence is used to describe packet dropouts among agents in a stochastic way. For deterministic packet losses, a switched system with stable and unstable subsystems is employed to model packet dropouts in a deterministic way. The purpose of this paper is to derive consensus criteria, such that linear multi-agent systems with sampled-data and packet losses can reach consensus. By means of the Lyapunov function approach and the decomposition method, the design problem of a distributed controller is solved in terms of convex optimization. The interplay among the allowable bound of the sampling interval, the probability of random packet losses, and the rate of deterministic packet losses are explicitly derived to characterize consensus conditions. The obtained criteria are closely related to the maximum eigenvalue of the Laplacian matrix versus the second minimum eigenvalue of the Laplacian matrix, which reveals the intrinsic effect of communication topologies on consensus performance. Finally, simulations are given to show the effectiveness of the proposed results.In this paper, the consensus problem is studied for a class of multi-agent systems with sampled data and packet losses, where random and deterministic packet losses are considered, respectively. For random packet losses, a Bernoulli-distributed white sequence is used to describe packet dropouts among agents in a stochastic way. For deterministic packet losses, a switched system with stable and unstable subsystems is employed to model packet dropouts in a deterministic way. The purpose of this paper is to derive consensus criteria, such that linear multi-agent systems with sampled-data and packet losses can reach consensus. By means of the Lyapunov function

The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design.

Science.gov (United States)

Giacomini, Elisa; Rupiani, Sebastiano; Guidotti, Laura; Recanatini, Maurizio; Roberti, Marinella

2016-01-01

The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potential in therapeutic and preventive application. Resveratrol, present in grapes and other food products, plays a role in the prevention of several human pathological processes and has been suggested as an anticancer agent. Moreover, recent evidence has revealed its potential effect on the aging process, diabetes and neurological dysfunction. Combretastatin A-4, from the bark of South African bush willow Combretum caffrum, also shows significant antitumor activity. Pterostilbene is closely related to resveratrol, sharing the same unique therapeutic potential as anti-inflammatory, antineoplastic and antioxidant agent. Therefore, research and development of stilbene-based medicinal chemistry have become rapidly evolving and increasingly active topics covering almost the whole range of therapeutic fields. In the present review, we provide an overview of the role of stilbenes in medicinal chemistry. In this context, we highlight the chemical methodologies adopted for the synthesis of stilbene derivatives, and outline the successful design of novel stilbene based hybrids in the field of cancer, Alzheimer's and other relevant diseases. This information may be useful in further design of stilbene-based molecules as new leads for the development of novel agents with clinical potential or as effective chemical probes to dissect biological processes.

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

Uniform Surface Modification of 3D Bioglass®-Based Scaffolds with Mesoporous Silica Particles (MCM-41) for Enhancing Drug Delivery Capability

Science.gov (United States)

Boccardi, Elena; Philippart, Anahí; Juhasz-Bortuzzo, Judith A.; Beltrán, Ana M.; Novajra, Giorgia; Vitale-Brovarone, Chiara; Spiecker, Erdmann; Boccaccini, Aldo R.

2015-01-01

The design and characterization of a new family of multifunctional scaffolds based on bioactive glass (BG) of 45S5 composition for bone tissue engineering and drug delivery applications are presented. These BG-based scaffolds are developed via a replication method of polyurethane packaging foam. In order to increase the therapeutic functionality, the scaffolds were coated with mesoporous silica particles (MCM-41), which act as an in situ drug delivery system. These sub-micron spheres are characterized by large surface area and pore volume with a narrow pore diameter distribution. The solution used for the synthesis of the silica mesoporous particles was designed to obtain a high-ordered mesoporous structure and spherical shape – both are key factors for achieving the desired controlled drug release. The MCM-41 particles were synthesized directly inside the BG-based scaffolds, and the drug-release capability of this combined system was evaluated. Moreover, the effect of MCM-41 particle coating on the bioactivity of the BG-based scaffolds was assessed. The results indicate that it is possible to obtain a multifunctional scaffold system characterized by high and interconnected porosity, high bioactivity, and sustained drug delivery capability. PMID:26594642

An Improved Consensus Linkage Map of Barley Based on Flow-Sorted Chromosomes and Single Nucleotide Polymorphism Markers

Directory of Open Access Journals (Sweden)

María Muñoz-Amatriaín

2011-11-01

Full Text Available Recent advances in high-throughput genotyping have made it easier to combine information from different mapping populations into consensus genetic maps, which provide increased marker density and genome coverage compared to individual maps. Previously, a single nucleotide polymorphism (SNP-based genotyping platform was developed and used to genotype 373 individuals in four barley ( L. mapping populations. This led to a 2943 SNP consensus genetic map with 975 unique positions. In this work, we add data from six additional populations and more individuals from one of the original populations to develop an improved consensus map from 1133 individuals. A stringent and systematic analysis of each of the 10 populations was performed to achieve uniformity. This involved reexamination of the four populations included in the previous map. As a consequence, we present a robust consensus genetic map that contains 2994 SNP loci mapped to 1163 unique positions. The map spans 1137.3 cM with an average density of one marker bin per 0.99 cM. A novel application of the genotyping platform for gene detection allowed the assignment of 2930 genes to flow-sorted chromosomes or arms, confirmed the position of 2545 SNP-mapped loci, added chromosome or arm allocations to an additional 370 SNP loci, and delineated pericentromeric regions for chromosomes 2H to 7H. Marker order has been improved and map resolution has been increased by almost 20%. These increased precision outcomes enable more optimized SNP selection for marker-assisted breeding and support association genetic analysis and map-based cloning. It will also improve the anchoring of DNA sequence scaffolds and the barley physical map to the genetic map.

Achieving consensus in environmental programs

International Nuclear Information System (INIS)

Kurstedt, H.A.; Jones, R.M.; Walker, J.A.; Middleman, L.I.

1989-01-01

In this paper, the authors describe a research effort on consensus tied to the Environmental Restoration Program (ERP) within the U.S. Department of Energy's Office of Defense Waste and Transportation Management (DWTM). They define consensus and explain why consensus decisions are not merely desirable but necessary in furthering ERP activities. As examples of their planned applied research, the authors first discuss nominal group technique as a representative consensus-generating tool, and conclude by describing the consensus-related mission of the Waste Management Review Group, established to conduct independent, third-party review of DWTM/ERP plans and activities

Achieving consensus in environmental programs

Energy Technology Data Exchange (ETDEWEB)

Kurstedt, Jr., H. A.; Jones, R. M.; Walker, J. A.; Middleman, L. I.

1989-01-01

In this paper, we describe a new research effort on consensus tied to the Environmental Restoration Program (ERP) within the US Department of Energy's Office of Defense Waste and Transportation Management (DWTM). We define consensus and explain why consensus decisions are not merely desirable but necessary in furthering ERP activities. As examples of our planned applied research, we first discuss Nominal Group Technique as a representative consensus-generating tool, and we conclude by describing the consensus-related mission of the Waste Management Review Group, established at Virginia Tech to conduct independent, third-party review of DWTM/ERP plans and activities. 10 refs.

Team Cooperation in a Network of Multi-Vehicle Unmanned Systems Synthesis of Consensus Algorithms

CERN Document Server

Semsar-Kazerooni, Elham

2013-01-01

Team Cooperation in a Network of Multi-Vehicle Unmanned Systems develops a framework for modeling and control of a network of multi-agent unmanned systems in a cooperative manner and with consideration of non-ideal and practical considerations. The main focus of this book is the development of “synthesis-based” algorithms rather than on conventional “analysis-based” approaches to the team cooperation, specifically the team consensus problems. The authors provide a set of modified “design-based” consensus algorithms whose optimality is verified through introduction of performance indices. This book also: Provides synthesis-based methodology for team cooperation Introduces a consensus-protocol optimized performance index  Offers comparisons for use of proper indices in measuring team performance Analyzes and predicts  performance of  previously designed consensus algorithms Analyses and predicts team behavior in the presence of non-ideal considerations such as actuator anomalies and faults as wel...

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.