1,721,037 research outputs found

    Properties of photo-cured poly(D,L-lactide) networks

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    Poly(D,L-lactide) is a degradable polymer with a long\ud history of use in medical applications. It is strong and\ud stiff and degrades over the course of months into lactic\ud acid, a body-own substance. In the field of tissue\ud engineering it is commonly used to fabricate scaffolds.\ud Stereolithography is a high resolution rapid prototyping\ud technique by which designed 3D objects can be built\ud using photo-initiated radical polymerisations. Poly(D,Llactide)\ud (PDLLA) networks can be obtained by photopolymerisation\ud of oligomers functionalised with\ud unsaturated groups.\ud In this work, PDLLA oligomers of varying architectures\ud (arm lengths, numbers of arms) were synthesised and\ud end-functionalised with methacrylate groups. These\ud macromers were photo-crosslinked in solution to yield\ud PDLLA networks of different architectures. The\ud influence of the network architecture on its physical\ud properties was studied

    Mechanical properties of advanced tissue engineering scaffold architectures

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    In tissue engineering, porous scaffolds are used as a temporal support for tissue regeneration\ud through cell adhesion, proliferation and differentiation. Besides applying a suitable material that is\ud both biocompatible and biodegradable, the architectural design of the porous scaffold can be of\ud essential for successful tissue regeneration. The architecture is of great influence on mechanical\ud properties and transport properties of nutrients and metabolites1

    A review on stereolithography and its applications in biomedical engineering

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    Stereolithography is a solid freeform technique (SFF) that was introduced in the late 1980s. Although many other techniques have been developed since then, stereolithography remains one of the most powerful and versatile of all SFF techniques. It has the highest fabrication accuracy and an increasing number of materials that can be processed is becoming available. In this paper we discuss the characteristic features of the stereolithography technique and compare it to other SFF techniques. The biomedical applications of stereolithography are reviewed, as well as the biodegradable resin materials that have been developed for use with stereolithography. Finally, an overview of the application of stereolithography in preparing porous structures for tissue engineering is given

    Gellan gum fluid gels as suspension media for 3D bioprinting of in vitro tissue models

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    Engineering 3-dimensional (3D), vascularised tissues for therapeutic applications, such as the testing of chemo-therapeutic drugs or organ replacement, remains a major challenge in human healthcare. Advances in biofabrication, specifically extrusion 3D bioprinting technologies have driven the development of complex tissue structures by increasing control over the spatial organisation of cells. Recently, the use of self-healing, viscoplastic fluids, referred to as suspension media, have been employed in combination with extrusion 3D printers in order to fabricate more biomimetic structures from soft water-rich materials. These suspension media have garnered interest as they provide the required support to prevent structural collapse of a printed material. In this work, suspension media were developed from sheared gels containing lower than 0.5 % (w/v) low acyl gellan gum. These gels formed a jammed particle network in which structures of arbitrary designs or discrete small volumes of cell-laden inks could be printed in 3D space. Rheological testing was performed on these gels to provide an understanding of their behaviour at typical bioprinting temperatures, showing these gels demonstrated viscoplasticity and self-healing abilities at temperatures up to 37 oC. To demonstrate the versatility of these gels to the tissue engineering field, they were supplemented with gelatin methacryloyl to enable retention of the suspension medium post-printing via photocuring. This approach was leveraged to permit fabrication of a large tissue model within a relatively short fabrication timeframe and to additionally fabricate synthetic microvascular-like networks by utilising the gellan gum particles to provide support to printed thermoreversible, sacrificial ink filaments, which were later hollowed post-curing of the medium

    Methacrylate-functionalized oligomers based on lactide, ε-\ud caprolactone and trimethylene carbonate for application in\ud stereo-lithography

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    Photo-curable biodegradable macromers were prepared by ring opening\ud polymerization of D,L-lactide (DLLA), ε-caprolactone (CL) and 1,3-trimethylene\ud carbonate (TMC) in the presence of glycerol or sorbitol as initiator and stannous octoate\ud as catalyst, and subsequent methacrylation of the terminal hydroxyl groups. These\ud methacrylated macromers, ranging in molecular weight from approximately 700 to 6000\ud g/mol, were cross-linked using ultraviolet (UV) light to form biodegradable networks.\ud Homogeneous networks with high gel contents were prepared. One of the resins based\ud on PTMC was used to prepare three-dimensional structures by stereo-lithography\ud using a commercially available apparatus

    Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures

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    Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury whilst recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled-density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3-E1 preosteoblast cellular response in an in vitro static plate and custom-designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter-layer lay-down angle and offset between layers, whilst maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size and permeability decreased, whilst computational fluid dynamics-modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (~45% to ~86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment

    Development of a novel polymeric osmotically triggered delayed release vaccine delivery device

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    In this work, a delayed release osmotically triggered delivery device was developed that was able to release a payload after a delay of approximately 21 days in a consistent and reproducible manner. The device was constructed out of a flexible polycaprolactone photo-cured network, which expelled up to 21.5 % of its total payload after burst, enabling close to bolus-like release profile. Characterisation of the factors that control the delay of release was also performed, with evidence demonstrating that it was advantageous to adjust material permeability and device wall thickness over manipulation of the osmogent concentration, in order to maintain burst reproducibility. The photo-cured polycaprolactone network was shown to be degradable under simulated physiological conditions, and there was no evidence of cytotoxicity after 11 days of direct contact with primary dermal fibroblasts. This study provides strong evidence to support further development of flexible biomaterials with the aim of continuing improvement of the device burst characteristics in order to provide the greatest chance of the devices succeeding with in-vivo vaccine booster delivery. Additionally, a polycaprolactone-based stereolithography resin was developed that retains a degree of semi-crystallinity, thus providing significantly improved toughness while retaining biocompatibility. Benzyl alcohol was shown to be a more suitable diluent than dioxane for the formulation of PCL macromer photo-curable resins. An improved automated dip-coat-curing machine for the production of the device tubular part was also constructed

    Gelatine methacrylamide-based hydrogels: An alternative three-dimensional cancer cell culture system

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    Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of the extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized and established as in vitro and in vivo spheroid-based models for ovarian cancer, reflecting the advanced disease stage of patients, with accumulation of multicellular spheroids in the tumour fluid (ascites). Polymer concentration (2.5–7% w/v) strongly influenced hydrogel stiffness (0.5 ± 0.2 kPa to 9.0 ± 1.8 kPa) but had little effect on solute diffusion. The diffusion coefficient of 70 kDa fluorescein isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3 times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA) and stiffness (3.4 kPa) allowed spheroid formation and high proliferation and metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM degradability reduced spheroid formation and proliferation rates. The incorporation of the ECM components laminin-411 and hyaluronic acid further stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre-cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer animal model was proven and led to tumour development and metastasis. These tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not the integrin antagonist ATN-161. While paclitaxel and its combination with ATN-161 resulted in a treatment response of 33–37.8%, ATN-161 alone had no effect on tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA combines relevant natural cues with tunable properties, providing an alternative, bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.No Full Tex

    Preparation of advanced porous structures by stereolithography for application in tissue engineering

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    Stereolithography is a solid freeform fabrication technique, with which computer-designed objects can be automatically fabricated from photo-curable polymer resins in a layer-by-layer manner. In tissue engineering, there is a need for porous structures with well-defined external geometries and internal pore architectures to serve as scaffolds, which are biodegradable support materials for the generation of new tissue by seeded cells. In this work we have developed several resins for use in a stereolithography apparatus to make such scaffolds. A poly(D,L-lactide)-based resin was prepared for making strong and rigid glassy materials, a poly(D,L-lactide-co--caprolactone)-based resin for flexible materials, a poly(ethylene glycol-co-D,L-lactide)-based resin for hydrogels and a resin based on poly(D,L-lactide) and micrometer-sized hydroxyapatite particles for composite materials suitable for bone repair. Using these resins, biodegradable structures with different designs were prepared with high precision and accuracy, as determined by micro-computed tomography. Their mechanical properties could be influenced by the choice of building material and by the architecture of the porous structure. Due to the well-defined architecture, the mechanical behaviour could be very well predicted using finite element modelling techniques. Designed gyroid structures prepared by stereolithography showed a permeability of one order of magnitude larger than salt-leached porous structures having similar porosity and pore size. This facilitated wetting and the homogeneous seeding of cells into the scaffolds, and enabled 5 days of static culture with high final cell densities in the core of 5 mm-sized gyroid scaffolds. The high freedom of design of the stereolithography technique also enabled the preparation of scaffolds with a gradient in pore size and porosity. In this way the flow profile throughout perfused scaffolds could be influenced by the pore architecture, and both homogeneous cell distributions as well as gradients therein could be accomplished using a perfusion bioreactor. The future use of stereolithography and the developed materials could lead to better solutions for regenerating failing tissues
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