In the last 30 days

• Open/close Toward engineering functional organ modules by additive manufacturing

  Francoise Marga et al 2012 Biofabrication 4 022001 Tag this article

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  Tissue engineering is emerging as a possible alternative to methods aimed at alleviating the growing demand for replacement tissues and organs. A major pillar of most tissue engineering approaches is the scaffold, a biocompatible network of synthetic or natural polymers, which serves as an extracellular matrix mimic for cells. When the scaffold is seeded with cells it is supposed to provide the appropriate biomechanical and biochemical conditions for cell proliferation and eventual tissue formation. Numerous approaches have been used to fabricate scaffolds with ever-growing complexity. Recently, novel approaches have been pursued that do not rely on artificial scaffolds. The most promising ones utilize matrices of decellularized organs or methods based on multicellular self-assembly, such as sheet-based and bioprinting-based technologies. We briefly overview some of the scaffold-free approaches and detail one that employs biological self-assembly and bioprinting. We describe the technology and its specific applications to engineer vascular and nerve grafts.

• Open/close Tissue engineering by self-assembly and bio-printing of living cells

  Karoly Jakab et al 2010 Biofabrication 2 022001 Tag this article

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  Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion.

• Open/close Two-photon polymerization-generated and micromolding-replicated 3D scaffolds for peripheral neural tissue engineering applications

  A Koroleva et al 2012 Biofabrication 4 025005 Tag this article

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  In this study, we explore the production of well-defined macroscopic scaffolds with two-photon polymerization (2PP) and their use as neural tissue engineering scaffolds. We also demonstrate that these 3D scaffolds can be replicated via soft lithography, which increases production efficiency. Photopolymerizable polylactic acid (PLA) was used to produce scaffolds by 2PP and soft lithography. We assessed the biocompatibility of these scaffolds using an SH-SY5Y human neuronal cell line and primary cultured rat Schwann cells (of direct relevance to the repair of nerve injuries). A Comet assay with SH-SY5Y human neuronal cells revealed minimal DNA damage after washing the photocured material for 7 days in ethanol. Additionally, thin films and 3D scaffolds of the photocured PLA sustained a high degree of Schwann cell purity (99%), enabled proliferation over 7 days and provided a suitable substrate for supporting Schwann cell adhesion such that bi-polar and tri-polar morphologies were observed. Evidence of orthogonally aligned and organized actin thin filaments and the formation of focal contacts were observed for the majority of Schwann cells. In summary, this work supports the use of PLA as a suitable material for supporting Schwann cell growth and in turn use of 3D soft lithography for the synthesis of neural scaffolds in nerve repair.

• Open/close Microfluidic hydrogels for tissue engineering

  Guo You Huang et al 2011 Biofabrication 3 012001 Tag this article

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  With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

• Open/close Direct laser writing of 3D scaffolds for neural tissue engineering applications

  V Melissinaki et al 2011 Biofabrication 3 045005 Tag this article

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  This study reports on the production of high-resolution 3D structures of polylactide-based materials via multi-photon polymerization and explores their use as neural tissue engineering scaffolds. To achieve this, a liquid polylactide resin was synthesized in house and rendered photocurable via attaching methacrylate groups to the hydroxyl end groups of the small molecular weight prepolymer. This resin cures easily under UV irradiation, using a mercury lamp, and under femtosecond IR irradiation. The results showed that the photocurable polylactide (PLA) resin can be readily structured via direct laser write (DLW) with a femtosecond Ti:sapphire laser and submicrometer structures can be produced. The maximum resolution achieved is 800 nm. Neuroblastoma cells were grown on thin films of the cured PLA material, and cell viability and proliferation assays revealed good biocompatibility of the material. Additionally, PC12 and NG108-15 neuroblastoma growth on bespoke scaffolds was studied in more detail to assess potential applications for neuronal implants of this material.

• Open/close Crosslinked electrospun PVA nanofibrous membranes: elucidation of their physicochemical, physicomechanical and molecular disposition

  Rubina P Shaikh et al 2012 Biofabrication 4 025002 Tag this article

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  The effects of modifying electrospun poly(vinyl alcohol) (PVA) nanofibers through crosslinking using glutaraldehyde (GA) are explored in this paper. Various concentrations of PVA solutions containing model drugs rifampicin (RIF) and isoniazid (INH) were electrospun and thereafter crosslinked using GA vapors. PVA nanofibers demonstrated high drug entrapment efficiency of 98.77% ± 1.384% and 95.07% ± 1.988% for the INH- and RIF-loaded PVA nanofibers, respectively. The surface morphology, molecular vibrational transitions, tensile attributes and in vitro drug release were characterized and supported by in silico molecular mechanics simulations. Results indicated that crosslinking caused a significant reduction in the rate of drug release where 81.11% ± 2.35% of INH and 59.31% ± 2.57% of RIF were released after 12 h. Tensile properties such as the ultimate strength and Young's modulus increased after crosslinking, caused by crosslinks forming between PVA nanofibers as was revealed through scanning electron microscopy analysis. Fourier Transform infrared analysis was conducted to further support the mode of crosslinking. Additionally, image processing analysis was carried out to quantify the effect of formulation variables on the morphology of nanofibers. Furthermore, the effect of GA-induced crosslinking and addition of drugs on the performance of electrospun fibers was further elucidated and conceptualized using a molecular mechanics assisted model building and energy refinement approach via molecular mechanics energy relationships by exploring the spatial disposition of energy-minimized molecular structures of the polymer, crosslinker and the drugs.

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

  Jinku Kim et al 2012 Biofabrication 4 025003 Tag this article

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  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.

• Open/close Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

  Feng Xu et al 2011 Biofabrication 3 034101 Tag this article

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  Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

• Open/close Biofabrication to build the biology–device interface

  Yi Liu et al 2010 Biofabrication 2 022002 Tag this article

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  The last century witnessed spectacular advances in both microelectronics and biotechnology yet there was little synergy between the two. A challenge to their integration is that biological and electronic systems are constructed using divergent fabrication paradigms. Biology fabricates bottom-up with labile components, while microelectronic devices are fabricated top-down using methods that are 'bio-incompatible'. Biofabrication—the use of biological materials and mechanisms for construction—offers the opportunity to span these fabrication paradigms by providing convergent approaches for building the bio–device interface. Integral to biofabrication are stimuli-responsive materials (e.g. film-forming polysaccharides) that allow directed assembly under near physiological conditions in response to device-imposed signals. Biomolecular engineering, through recombinant technology, allows biological components to be endowed with information for assembly (e.g. encoded in a protein's amino acid sequence). Finally, self-assembly and enzymatic assembly provide the mechanisms for construction over a hierarchy of length scales. Here, we review recent advances in the use of biofabrication to build the bio–device interface. We anticipate that the biofabrication toolbox will expand over the next decade as more researchers enlist the unique construction capabilities of biology. Further, we look forward to observing the application of this toolbox to create devices that can better diagnose disease, detect pathogens and discover drugs. Finally, we expect that biofabrication will enable the effective interfacing of biology with electronics to create implantable devices for personalized and regenerative medicine.

• Open/close Biofilm formation on nanostructured titanium oxide surfaces and a micro/nanofabrication-based preventive strategy using colloidal lithography

  Ajay Vikram Singh et al 2012 Biofabrication 4 025001 Tag this article

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  The contamination of implant devices as a result of biofilm formation through bacterial infection has instigated major research in this area, particularly to understand the mechanism of bacterial cell/implant surface interactions and their preventions. In this paper, we demonstrate a controlled method of nanostructured titanium oxide surface synthesis using supersonic cluster beam depositions. The nanoscale surface characterization using atomic force microscopy and a profilometer display a regulated evolution in nanomorphology and physical properties. X-ray photoelectron spectroscopy analyses display a stoichiometric nanostructured TiO ₂ film. Measurement of the water contact angle shows a nominal increase in the hydrophilic nature of ns-TiO ₂ films, whereas the surface energy increases with decreasing contact angle. Bacterial species Staphylococcus aureus and Escherichia coli interaction with nanostructured surfaces shows an increase in adhesion and biofilm formation with increasing nanoscale morphological properties. Conversely, limiting ns-TiO ₂ film distribution to micro/nanopatterned designed substrates integrated with bovine serum albumin functionalization leads to a reduction in biofilm formations due to a globally decreased bacterial cell–surface interaction area. The results have potential implications in inhibiting bacterial colonization and promoting mammalian cell–implant interactions.