Design, safety and efficacy evaluation of gemcitabine-eluting nanoyarn-integrated heparinized self expanding metallic stents for long-term management of malignant biliary obstruction.

Malignant biliary obstruction presents a significant therapeutic challenge and has serious consequences including cholangitis and death. Clinically, biliary stenting using self-expanding metallic- stent(SEMS) relieves this obstruction. However, stent occlusion occurs with time due to tumor/epithelial in-growth and bacterial colonization.

Efficacy of Lysostaphin functionalized silicon catheter for the prevention of Staphylococcus aureus biofilm.

Staphylococcus aureus readily forms biofilms on tissue and indwelling catheter surfaces. These biofilms are resistant to antibiotics. Consequently, effective prevention and treatment strategies against staphylococcal biofilms are actively being pursued over the past two decades.

Smart Design for Hybrid Bioprinting of Scalable and Viable Tissue Constructs.

Hybrid bioprinting uses sequential printing of melt-extruded biodegradable thermoplastic polymer and cell-encapsulated bioink in a predesigned manner using high- and low-temperature print heads for the fabrication of robust three-dimensional (3D) biological constructs. However, the high-temperature print head and melt-extruded polymer cause irreversible thermal damage to the bioprinted cells, and it affects viability and functionality of 3D bioprinted biological constructs. Thus, there is an urgent need to develop innovative approaches to protect the bioprinted cells, coming into contact or at close proximities to the melt-extruded thermoplastic polymer and the high-temperature print head during hybrid bioprinting.

Development and characterisation of suitably bioengineered microfibrillar matrix-based 3D prostate cancer model fordrug testing.

Bioengineered 3D models that can mimic patient-specific pathologiesare valuable tools for developing and validating anticancer therapeutics. In this study, microfibrillar matrices with unique structural and functional properties were fabricated as 3D spherical and disc-shaped scaffolds with highly interconnected pores and the potential of the newly developed scaffolds for developing prostate cancer model has been investigated. The newly developed scaffolds showed improved cell retention upon seeding with cancer cells compared to conventional electrospun scaffolds.

Human Adipose-Derived Mesenchymal Stem Cell-Secreted Extracellular Matrix Coating on a Woven Nanotextile Vascular Patch for Improved Endothelial Cell Response.

Biomedical implants possessing the structural and functional characteristics of extracellular matrix (ECM) are pivotal for vascular applications. This study investigated the potential of recreating a natural ECM-like structural and functional environment on the surface of biodegradable polymeric nanotextiles for vascular implants. Human adipose-derived mesenchymal stem cells (MSCs) were grown on a suitably engineered polycaprolactone (PCL) nanofibrous textile and were allowed to modify its surface through the deposition of MSC-specific ECM.

Bioengineered 3D microfibrous-matrix modulates osteopontin release from MSCs and facilitates the expansion of hematopoietic stem cells.

The osteopontin (OPN) released from mesenchymal stem cells (MSCs) undergoing lineage differentiation can negatively influence the expansion of hematopoietic stem cells (HSCs) in coculture systems developed for expanding HSCs. Therefore, minimizing the amount of OPN in the coculture system is important for the successful ex vivo expansion of HSCs. Toward this goal, a bioengineered three dimensional (3D) microfibrous-matrix that can maintain MSCs in less OPN-releasing conditions has been developed, and its influence on the expansion of HSCs has been studied.

Soft Hydrogel Environments that Facilitate Cell Spreading and Aggregation Preferentially Support Chondrogenesis of Adult Stem Cells.

Mesenchymal stem/stromal cells (MSCs) represent a promising cell type for treating damaged synovial joints. The therapeutic potential of MSCs will be facilitated by the engineering of biomaterial environments capable of directing their fate. Here the interplay between matrix elasticity and cell morphology in regulating the chondrogenic differentiation of MSCs when seeded onto or encapsulated within hydrogels made of interpenetrating networks (IPN) of alginate and collagen type I is explored.

Spatial Presentation of Tissue-Specific Extracellular Matrix Components along Electrospun Scaffolds for Tissue Engineering the Bone-Ligament Interface.

The bone-ligament interface transitions from a highly organized type I collagen rich matrix to a nonmineralized fibrocartilage region and finally to a mineralized fibrocartilage region that interfaces with the bone. Therefore, engineering the bone-ligament interface requires a biomaterial substrate capable of maintaining or directing the spatially defined differentiation of multiple cell phenotypes. To date the appropriate combination of biophysical and biochemical factors that can be used to engineer such a biomaterial substrate remain unknown.

nCP:Fe-A Biomineral Magnetic Nanocontrast Agent for Tracking Implanted Stem Cells in Brain Using MRI.

tracking of transplanted stem cells to monitor their migration, biodistribution, and engraftment in the host tissue is important for assessing the efficacy of stem cell therapeutics. Here, we report a biomineral nanocontrast agent, iron doped calcium phosphate nanoparticles (nCP:Fe), for the tracking of stem cells in brain using magnetic resonance imaging (MRI). We have synthesized ∼100 nm sized nCP nanoparticles doped with 9.

Electrospinning of highly porous yet mechanically functional microfibrillar scaffolds at the human scale for ligament and tendon tissue engineering.

Electrospun fibers offer tremendous potential for tendon and ligament tissue engineering, yet developing porous scaffolds mimicking the size, stiffness and strength of human tissues remains a challenge. Previous studies have rolled, braided, or stacked electrospun sheets to produce three-dimensional (3D) scaffolds with tailored sizes and mechanical properties. A common limitation with such approaches is the development of low porosity scaffolds that impede cellular infiltration into the body of the implant, thereby limiting their regenerative potential.

Hypoxia mimicking hydrogels to regulate the fate of transplanted stem cells.

Controlling the phenotype of transplanted stem cells is integral to ensuring their therapeutic efficacy. Hypoxia is a known regulator of stem cell fate, the effects of which can be mimicked using hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors such as dimethyloxalylglycine (DMOG). By releasing DMOG from mesenchymal stem cell (MSC) laden alginate hydrogels, it is possible to stabilize HIF-1α and enhance its nuclear localization.

Engineering large cartilage tissues using dynamic bioreactor culture at defined oxygen conditions.

Mesenchymal stem cells maintained in appropriate culture conditions are capable of producing robust cartilage tissue. However, gradients in nutrient availability that arise during three-dimensional culture can result in the development of spatially inhomogeneous cartilage tissues with core regions devoid of matrix. Previous attempts at developing dynamic culture systems to overcome these limitations have reported suppression of mesenchymal stem cell chondrogenesis compared to static conditions.

Modulating microfibrillar alignment and growth factor stimulation to regulate mesenchymal stem cell differentiation.

Unlabelled: The ideal tissue engineering (TE) strategy for ligament regeneration should recapitulate the bone - calcified cartilage - fibrocartilage - soft tissue interface. Aligned electrospun-fibers have been shown to guide the deposition of a highly organized extracellular matrix (ECM) necessary for ligament TE. However, recapitulating the different tissues observed in the bone-ligament interface using such constructs remains a challenge.

Three-Dimensional Bioprinting of Polycaprolactone Reinforced Gene Activated Bioinks for Bone Tissue Engineering.

Regeneration of complex bone defects remains a significant clinical challenge. Multi-tool biofabrication has permitted the combination of various biomaterials to create multifaceted composites with tailorable mechanical properties and spatially controlled biological function. In this study we sought to use bioprinting to engineer nonviral gene activated constructs reinforced by polymeric micro-filaments.

Simple Radical Polymerization of Poly(Alginate-Graft-N-Isopropylacrylamide) Injectable Thermoresponsive Hydrogel with the Potential for Localized and Sustained Delivery of Stem Cells and Bioactive Molecules.

In this study, thermoresponsive copolymers that are fully injectable, biocompatible, and biodegradable and are synthesized via graft copolymerization of poly(N-isopropylacrylamide) onto alginate using a free-radical reaction are presented. This new synthesis method does not involve multisteps or associated toxicity issues, and has the potential to reduce scale-up difficulties. Chemical and physical analyses verify the resultant graft copolymer structure.

Mesenchymal stem cell fate following non-viral gene transfection strongly depends on the choice of delivery vector.

Unlabelled: Controlling the phenotype of mesenchymal stem cells (MSCs) through the delivery of regulatory genes is a promising strategy in tissue engineering (TE). Essential to effective gene delivery is the choice of gene carrier. Non-viral delivery vectors have been extensively used in TE, however their intrinsic effects on MSC differentiation remain poorly understood.

Hierarchically Structured Electrospun Scaffolds with Chemically Conjugated Growth Factor for Ligament Tissue Engineering.

The anterior cruciate ligament (ACL) of the knee is vital for proper joint function and is commonly ruptured during sports injuries or car accidents. Due to a lack of intrinsic healing capacity and drawbacks with allografts and autografts, there is a need for a tissue-engineered ACL replacement. Our group has previously used aligned sheets of electrospun polycaprolactone nanofibers to develop solid cylindrical bundles of longitudinally aligned nanofibers.

RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo.

A range of bone regeneration strategies, from growth factor delivery and/or mesenchymal stem cell (MSC) transplantation to endochondral tissue engineering, have been developed in recent years. Despite their tremendous promise, the clinical translation and future use of many of these strategies is being hampered by concerns such as off target effects associated with growth factor delivery. Therefore the overall objective of this study was to investigate the influence of alpha-tricalcium phosphate (α-TCP) nanoparticle delivery into MSCs using an amphipathic cell penetrating peptide RALA, on osteogenesis in vitro and both intramembranous and endochondral bone formation in vivo.

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

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.

3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering.

The ability to print defined patterns of cells and extracellular-matrix components in three dimensions has enabled the engineering of simple biological tissues; however, bioprinting functional solid organs is beyond the capabilities of current biofabrication technologies. An alternative approach would be to bioprint the developmental precursor to an adult organ, using this engineered rudiment as a template for subsequent organogenesis in vivo. This study demonstrates that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp adhesion peptides.

Bone Tissue Engineering with Multilayered Scaffolds-Part I: An Approach for Vascularizing Engineered Constructs In Vivo.

Obtaining functional capillaries through the bulk has been identified as a major challenge in tissue engineering, particularly for critical-sized defects. In the present study, a multilayered scaffold system was developed for bone tissue regeneration, designed for through-the-thickness vascularization of the construct. The basic principle of this approach was to alternately layer mesenchymal stem cell-seeded nanofibers (osteogenic layer) with microfibers or porous ceramics (osteoconductive layer), with an intercalating angiogenic zone between the two and with each individual layer in the microscale dimension (100-400 μm).

Bone Tissue Engineering with Multilayered Scaffolds-Part II: Combining Vascularization with Bone Formation in Critical-Sized Bone Defect.

Our previous in vivo study showed that multilayered scaffolds made of an angiogenic layer embedded between an osteogenic layer and an osteoconductive layer, with layer thickness in the 100-400 μm range, resulted in through-the-thickness vascularization of the construct even in the absence of exogenous endothelial cells. The angiogenic layer was a collagen-fibronectin gel, and the osteogenic layer was made from nanofibrous polycaprolactone while the osteoconductive layer was made either from microporous hydroxyapatite or microfibrous polycaprolactone. In this follow-up study, we implanted these acellular and cellular multilayered constructs in critical-sized rat calvarial defects and evaluated their vascularization and bone formation potential.

Biocompatible magnetite/gold nanohybrid contrast agents via green chemistry for MRI and CT bioimaging.

Magnetite/gold (Fe(3)O(4)/Au) hybrid nanoparticles were synthesized from a single iron precursor (ferric chloride) through a green chemistry route using grape seed proanthocyanidin as the reducing agent. Structural and physicochemical characterization proved the nanohybrid to be crystalline, with spherical morphology and size ~35 nm. Magnetic resonance imaging and magnetization studies revealed that the Fe(3)O(4) component of the hybrid provided superparamagnetism, with dark T(2) contrast and high relaxivity (124.

Dynamic contrast-enhanced and T2-weighted magnetic resonance imaging study of the correlation between tumour angiogenesis and growth kinetics.

Accumulating evidence indicates that tumour growth is angiogenesis-dependent. Non-invasive assessment of the relationship between tumour growth and associated angiogenesis is essential for diagnosis and for therapeutic interventions. We utilized a combination of high-resolution T2-weighted and dynamic contrast-enhanced magnetic resonance imaging to investigate the dynamics of angiogenesis during tumour growth in a mouse tumour model expressing Epstein-Barr virus-encoded latent membrane protein 1 isolated from a nasopharyngeal carcinoma in Taiwan.