248 research outputs found

    ARTIFICIAL SYNTHETIC SCAFFOLDS FOR TISSUE ENGINEERING APPLICATION EMPHASIZING THE ROLE OF BIOPHYSICAL CUES

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    The mechanotransduction of cells is the intrinsic ability of cells to convert the mechanical signals provided by the surrounding matrix and other cells into biochemical signals that affect several distinct processes such as tumorigenesis, wound healing, and organ formation. The use of biomaterials as an artificial scaffold for cell attachment, differentiation and proliferation provides a tool to modulate and understand the mechanotransduction pathways, develop better in vitro models and clinical remedies. The effect of topographical cues and stiffness was investigated in fibroblasts using polycaprolactone (PCL)- Polyaniline (PANI) based scaffolds that were fabricated using a self-assembly method and electrospinning. Through this method, scaffolds of different topography and stiffness were fabricated with similar surface chemistries. The effect of scaffold morphologies on the cells were investigated. PCL scaffolds of three distinct morphologies- honeycomb, aligned and mesh were used with similar surface chemistry to investigate the changes in cell behavior of breast, renal, lung and bladder cancer to the physical cues. Selective adhesion and localization of cells to specific morphologies were determined. In order to demonstrate the scaffold as a source of biochemical signals, ManCou-H, capable of targeting the fructose-specific glucose transporter GLUT5 was electrospun with the scaffolds of different morphologies. The PCL scaffolds were used as the backbone to release ManCou-H and changes in protein expression and metabolic activity was characterized. The findings made available through this research will help in the design of better cell-specific in vitro model systems to better understand cellular responses to clinical therapies, assess cell response to specific mechanical and chemical cues

    Multi-functional electrospun nanofibers from polymer blends for scaffold tissue engineering

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    Electrospinning and polymer blending have been the focus of research and the industry for their versatility, scalability, and potential applications across many different fields. In tissue engineering, nanofiber scaffolds composed of natural fibers, synthetic fibers, or a mixture of both have been reported. This review reports recent advances in polymer blended scaffolds for tissue engineering and the fabrication of functional scaffolds by electrospinning. A brief theory of electrospinning and the general setup as well as modifications used are presented. Polymer blends, including blends with natural polymers, synthetic polymers, mixture of natural and synthetic polymers, and nanofiller systems, are discussed in detail and reviewed

    Current Advances in Anisotropic Structures for Enhanced Osteogenesis

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    Bone defects are a challenge to healthcare systems, as the aging population experiences an increase in bone defects. Despite the development of biomaterials for bone fillers and scaffolds, there is still an unmet need for a bone-mimetic material. Cortical bone is highly anisotropic and displays a biological liquid crystalline (LC) arrangement, giving it exceptional mechanical properties and a distinctive microenvironment. However, the biofunctions, cell-tissue interactions, and molecular mechanisms of cortical bone anisotropic structure are not well understood. Incorporating anisotropic structures in bone-facilitated scaffolds has been recognised as essential for better outcomes. Various approaches have been used to create anisotropic micro/nanostructures, but biomimetic bone anisotropic structures are still in the early stages of development. Most scaffolds lack features at the nanoscale, and there is no comprehensive evaluation of molecular mechanisms or characterisation of calcium secretion. This manuscript provides a review of the latest development of anisotropic designs for osteogenesis and discusses current findings on cell-anisotropic structure interactions. It also emphasises the need for further research. Filling knowledge gaps will enable the fabrication of scaffolds for improved and more controllable bone regeneration

    Electrospinning and emerging healthcare and medicine possibilities

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    Electrospinning forms fibers from either an electrically charged polymer solution or polymer melt. Over the past decades, it has become a simple and versatile method for nanofiber production. Hence, it has been explored in many different applications. Commonly used electrospinning assembles fibers from polymer solutions in various solvents, known as solution electrospinning, while melt and near-field electrospinning techniques enhance the versatility of electrospinning. Adaption of additive manufacturing strategy to electrospinning permits precise fiber deposition and predefining pattern construction. This manuscript critically presents the potential of electrospun nanofibers in healthcare applications. Research community drew impetus from the similarity of electrospun nanofibers to the morphology and mechanical properties of fibrous extracellular matrices (ECM) of natural human tissues. Electrospun nanofibrous scaffolds act as ECM analogs for specific tissue cells, stem cells, and tumor cells to realize tissue regeneration, stem cell differentiation, and in vitro tumor model construction. The large surface-to-volume ratio of electrospun nanofibers offers a considerable number of bioactive agents binding sites, which makes it a promising candidate for a number of biomedical applications. The applications of electrospinning in regenerative medicine, tissue engineering, controlled drug delivery, biosensors, and cancer diagnosis are elaborated. Electrospun nanofiber incorporations in medical device coating, in vitro 3D cancer model, and filtration membrane are also discussed

    Precisely Assembled Nanofiber Arrays as a Platform to Engineer Aligned Cell Sheets for Biofabrication

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    A hybrid cell sheet engineering approach was developed using ultra-thin nanofiber arrays to host the formation of composite nanofiber/cell sheets. It was found that confluent aligned cell sheets could grow on uniaxially-aligned and crisscrossed nanofiber arrays with extremely low fiber densities. The porosity of the nanofiber sheets was sufficient to allow aligned linear myotube formation from differentiated myoblasts on both sides of the nanofiber sheets, in spite of single-side cell seeding. The nanofiber content of the composite cell sheets is minimized to reduce the hindrance to cell migration, cell-cell contacts, mass transport, as well as the foreign body response or inflammatory response associated with the biomaterial. Even at extremely low densities, the nanofiber component significantly enhanced the stability and mechanical properties of the composite cell sheets. In addition, the aligned nanofiber arrays imparted excellent handling properties to the composite cell sheets, which allowed easy processing into more complex, thick 3D structures of higher hierarchy. Aligned nanofiber array-based composite cell sheet engineering combines several advantages of material-free cell sheet engineering and polymer scaffold-based cell sheet engineering; and it represents a new direction in aligned cell sheet engineering for a multitude of tissue engineering applications

    Cell patterning via optimized dielectrophoretic force within hexagonal electrodes in vitro for skin tissue engineering

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    Abstract(#br)Tissue reconstruction through in vitro cell seeding is a popular method for tissue engineering. In this paper, we proposed a thin-layer structure consisting of multiple hexagons for the regeneration of skin tissue. Cells could be seeded and cultured within the structure via dielectrophoresis (DEP) actively. A thin layer of the structure was fabricated with biocompatible medical-grade stainless steel via precise laser cutting. The fabricated layers were stacked together to form a 3D electrode pair, which could be used to generate a 3D electric field. Thus, the suspended cells within the structure could be patterned via DEP manipulation. The input voltage was examined and optimized to ensure cell viability and patterning efficiency during the DEP manipulation process. As soon..

    Conception et étude de microsystèmes avancés pour la recherche de cellules souches et de cellules cancéreuses.

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    This work aimed to provide new tools and methods that can be used for advanced studies of stem cells and cancer cells. We first developed a patch method for off-ground culture and differentiation of human induced pluripotent stem cells (hiPSCs). The culture patch we proposed consists of crosslinked monolayer gelatin nanofibers on a honeycomb frame to ensure minimal exogenous material contact and maximum permeability. Then, we demonstrated the formation of cardiac tissue constructs and motor neurons on the patch, started from embryoid-body like and monolayer hiPSC colonies, respectively. We also developed a microfluidic device with integrated filter for isolation of circulating tumor cells (CTCs), showing high capture performances in terms of efficiency, selectivity and cell viability. Finally, we evaluated the anti-cancer drug effect on the formation of tumor spheroids by using microfabricated agarose multi-wells. All together, we progressed in micro-engineering toward large scale applications.Ce travail a pour but de mettre au point des nouvelles méthodes pour la recherche avancée sur les cellules souches et les cellules cancéreuses. Nous avons d'abord développé une méthode de patch pour la culture et la différentiation des cellules souches pluripotentes induites humain (hiPSCs) "hors sol". Ce patch de culture est constitué des monocouches de nanofibres réticulées de gélatine sur un support en nid d'abeilles pour assurer un minimum de contact de matériel exogène et un maximum de perméabilité. Puis, nous avons démontré la formation des tissues cardiaques et des neurones moteurs sur le patch, partis de colonies des hiPSCs en forme d'embryoïdes et de monocouches respectivement. Nous avons également développé un dispositif microfluidique avec filtre intégré pour isoler les cellules tumorales circulantes (CTCs), montrant une haute performance de capture en termes d'efficacité, de sélectivité et de viabilité cellulaire. Enfin, nous avons évalué l'effet de drogue anticancéreuse à la formation des sphéroïdes tumoraux en utilisant des multi-puits d'agarose micro-fabriqués. Tous ensembles, nous avons progressé dans la micro-ingénierie vers des applications à grande échelle

    3D Jet Writing - Controlled Deposition of Multicomponent Electrospun Fibers in Three Dimensional Space.

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    Electrospinning is a fiber fabrication technique which has potential use in applications ranging from filters and sensors to regenerative medicine. Generation of multi-component fibers and particles is possible through the use of a technique called electrohydrodynamic co-jetting. Despite the many applications, the process suffers from two main limiting factors. First, the reliance on a bicompartmental fluid interface inherently limits the scalability of the system. Secondly, the random fiber placement resulting from a process instability leads to limited pore sizes and uncontrollable 3D architectures. Herein, both of these factors are addressed independently. Scalability was addressed by creating a device which creates an extended fluid interface composed of two polymer solutions. This method was shown to produce bicompartmental fibers and particles at throughputs in excess of 30 times greater than traditional methods while retaining consistent fiber size distributions. Next, a method of completely eliminating the whipping instabilities associated with the electrospinning process, called 3D jet writing, was shown to be capable of perfectly stacking of fibers on top of one another. This process utilizes radially directed electric fields to dampen the formation of whipping instabilities, and a moving collection electrode to produce 3D fiber geometries. Deposition of fiber lines within approximately 15 µm is achieved using this system, making direct writing of fiber stacks within 0.3° of perfectly parallel, and 1.1° of perpendicular, and fabrication of three-dimensional scaffolds with regular tessellated prismatic pore architectures possible with this technique. The precision afforded by this technique was used to create 3D high-density stem cell culture environments which contain up to 1.4 million cells/mm3 polymer material, with 96% of the scaffold volume consisting of open area for 3D cell growth. These scaffolds allow for 3D cell culture to be tessellated across large areas, addressing common limitations associated with other 3D culture techniques. When differentiated osteogenically, stem cell microtissues can promote healing of calvarial defects in mice, producing on average over three times the new bone volume compared to the control groups. Similar tessellated differentiated stem cell microtissues were also able to simulate a diseased tissue by promoting metastasis in anomalous anatomic sites in 5/5 cases.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135748/1/jjordahl_1.pd

    The influence of spatial scaffold properties on the interaction between cells and embedded growth factors

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    While modern-day healthcare continues to improve in terms of available treatments and life expectancy in many countries, increasing costs of providing medical services to aging populations place these systems under increasingly severe pressure. With continuing increases in chronic afflictions and ailments related to old age, more cost-efficient and long-term solutions are needed to meet these challenges.Regenerative medicine offers the potential for more effective long-term treatments, but is hindered by the high cost of the desired treatments in terms of development and implementation, owing to the complexity of the living materials used for such therapies.The work described in this thesis focuses on improving the level of control over the local cellular environment in order to reduce the need for costly materials (especially growth factors). Both surface topology and immobilization of growth factors have previously been shown to have an impact, and this research investigates potential interaction between these aspects. Patterning and immobilization of bio-active compounds are combined for the culture of human mesenchymal stem cells on surfaces with differently scaled patterns and concentrations of immobilized TGF-β1.Initial work focused on the creation of patterned surfaces with feature sizes ranging from 1 to 50 µm. Patterns were successfully produced in Poly (Ethylene Glycol), Polystyrene and Polycaprolactone surfaces using a microparticle-based moulding process.Further work resulted in the successful immobilization of TGF-β1 onto chemically modified surfaces, chiefly Polycaprolactone. Proteins were successfully immobilized onto Polycaprolactone surfaces at concentrations up to 4 pmol/cm2, with exact concentrations dependent on the parameters of the immobilization process.Finally, the developed methods were combined in a hybrid experiment using both patterned surfaces and growth factor immobilization. Results demonstrated a probable link between surface patterning and the effectiveness of immobilized growth factors, although further work is needed to more accurately describe any underlying processes.</div

    Cardiovascular 3D bioprinting:A review on cardiac tissue development

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    Cardiovascular diseases such as myocardial infarction account for millions of worldwide deaths annually. Cardiovascular tissues constitute a highly organized and complex three-dimensional (3D) structure that makes them hard to fabricate in a biomimetic manner by conventional scaffold fabrication methods. 3D bioprinting has been introduced as a novel cell-based method in the last two decades due to its ability to recapitulate cell density, multicellular architecture, physiochemical environment, and vascularization of biological constructs with accurate designs. This review article aims to provide a comprehensive outlook to obtain cardiovascular functional tissues from the engineering of bioinks comprising cells, hydrogels, and biofactors to bioprinting techniques and relevant biophysical stimulations responsible for maturation and tissue-level functions. Also, cardiac tissue 3D bioprinting investigations and further discussion over its challenges and perspectives are highlighted in this review article
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